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9. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Strom, Marika, Wheelock, Asa M., Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frederic, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlé, Sven Erik, Adcock, Ian M., Wheelock, Craig E., Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Strom, Marika, Wheelock, Asa M., Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frederic, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlé, Sven Erik, Adcock, Ian M., and Wheelock, Craig E.

Abstract

Introduction: Asthma is a heterogeneous disease with poorly defined phenotypes. Severe asthmatics often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. Methods: Baseline urine was collected prospectively from healthy participants (n=100), mild-to-moderate asthmatics (n=87) and severe asthmatics (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from severe asthmatics (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. Results: Ninety metabolites were identified, with 40 significantly altered (p<0.05, FDR<0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and mild-to-moderate asthmatics differed significantly from severe asthmatics (p=2.6×10−20), OCS-treated asthmatics differed significantly from non-treated (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. Conclusions: This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the necessity to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighti

Published
2022

12. Integration of gene expression and DNA methylation identifies epigenetically controlled modules related to PM2.5 exposure

Author

Medicina preventiva y salud pública, Prebentzio medikuntza eta osasun publikoa, Merid, Simon Kebede, Bustamante, Mariona, Standl, Marie, Sunyer, Jordi, Heinrich, Joachim, Lemonnier, Nathanael, Aguilar, Daniel, Antó, Josep Maria, Bousquet, Jean, Santa Marina, Loreto, Lertxundi Manterola, Aitana, Bergstrom, Anna, Kull, Inger, Wheelock, Asa M., Koppelman, Gerard H., Melen, Erik, Gruzieva, Olena, Medicina preventiva y salud pública, Prebentzio medikuntza eta osasun publikoa, Merid, Simon Kebede, Bustamante, Mariona, Standl, Marie, Sunyer, Jordi, Heinrich, Joachim, Lemonnier, Nathanael, Aguilar, Daniel, Antó, Josep Maria, Bousquet, Jean, Santa Marina, Loreto, Lertxundi Manterola, Aitana, Bergstrom, Anna, Kull, Inger, Wheelock, Asa M., Koppelman, Gerard H., Melen, Erik, and Gruzieva, Olena

Abstract

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 mu m in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.

Published
2021

13. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Strom, Marika, Wheelock, Asa M., Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frederic, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlé, Sven Erik, Adcock, Ian M., Wheelock, Craig E., Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Strom, Marika, Wheelock, Asa M., Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frederic, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlé, Sven Erik, Adcock, Ian M., and Wheelock, Craig E.

Abstract

Introduction: Asthma is a heterogeneous disease with poorly defined phenotypes. Severe asthmatics often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. Methods: Baseline urine was collected prospectively from healthy participants (n=100), mild-to-moderate asthmatics (n=87) and severe asthmatics (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from severe asthmatics (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. Results: Ninety metabolites were identified, with 40 significantly altered (p<0.05, FDR<0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and mild-to-moderate asthmatics differed significantly from severe asthmatics (p=2.6×10−20), OCS-treated asthmatics differed significantly from non-treated (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. Conclusions: This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the necessity to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighti

Published
2021

14. Distal Lung Microenvironment Triggers Release of Mediators Recognized as Potential Systemic Biomarkers for Idiopathic Pulmonary Fibrosis

Author

Kalafatis, Dimitrios, Loefdahl, Anna, Näsman, Per, Dellgren, Goeran, Wheelock, Asa M., Elowsson Rendin, Linda, Skoeld, Magnus, Westergren-Thorsson, Gunilla, Kalafatis, Dimitrios, Loefdahl, Anna, Näsman, Per, Dellgren, Goeran, Wheelock, Asa M., Elowsson Rendin, Linda, Skoeld, Magnus, and Westergren-Thorsson, Gunilla

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy controls. We demonstrate how proteins elevated in the ex vivo model (e.g., MMP7), and other serum proteins found elevated in IPF patients such as HGF, VEGFA, MCP-3, IL-6 and TNFRSF12A, are associated with disease severity and progression and their response to antifibrotic treatment. Our study supports the model's applicability in studying mechanisms involved in IPF and provides additional evidence for both established and potentially new biomarkers in IPF., QC 20220127

Published
2021
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15. Urinary Leukotriene E-4 and Prostaglandin D-2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation A Clinical Observational Study

Author

Kolmert, Johan, Gomez, Cristina, Balgoma, David, Sjodin, Marcus, Bood, Johan, Konradsen, Jon R., Ericsson, Magnus, Thorngren, John-Olof, James, Anna, Mikus, Maria, Sousa, Ana R., Riley, John H., Bates, Stewart, Bakke, Per S., Pandis, Ioannis, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Behndig, Annelie, Shaw, Dominick E., Knowles, Richard G., Holweg, Cecile T. J., Wheelock, Asa M., Dahlen, Barbro, Nordlund, Bjorn, Alving, Kjell, Hedlin, Gunilla, Chung, Kian Fan, Adcock, Ian M., Sterk, Peter J., Djukanovic, Ratko, Dahlen, Sven-Erik, Wheelock, Craig E., Kolmert, Johan, Gomez, Cristina, Balgoma, David, Sjodin, Marcus, Bood, Johan, Konradsen, Jon R., Ericsson, Magnus, Thorngren, John-Olof, James, Anna, Mikus, Maria, Sousa, Ana R., Riley, John H., Bates, Stewart, Bakke, Per S., Pandis, Ioannis, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Behndig, Annelie, Shaw, Dominick E., Knowles, Richard G., Holweg, Cecile T. J., Wheelock, Asa M., Dahlen, Barbro, Nordlund, Bjorn, Alving, Kjell, Hedlin, Gunilla, Chung, Kian Fan, Adcock, Ian M., Sterk, Peter J., Djukanovic, Ratko, Dahlen, Sven-Erik, and Wheelock, Craig E.

Abstract

Rationale: New approaches are needed to guide personalized treatment of asthma. Objectives: To test if urinary eicosanoid metabolites can direct asthma phenotyping. Methods: Urinary metabolites of prostaglandins (PGs), cysteinyl leukotrienes (CysLTs), and isoprostanes were quantified in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy control participants. Validation was performed internally in 302 participants with SA followed up after 12-18 months and externally in 95 adolescents with asthma. Measurement and Main Results: Metabolite concentrations in healthy control participants were unrelated to age, body mass index, and sex, except for the PGE(2) pathway. Eicosanoid concentrations were generally greater in participants with MMA relative to healthy control participants, with further elevations in participants with SA. However, PGE(2) metabolite concentrations were either the same or lower in male nonsmokers with asthma than in healthy control participants. Metabolite concentrations were unchanged in those with asthma who adhered to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas those with SA treated with omalizumab had lower concentrations of LTE4 and the PGD(2) metabolite 2,3-dinor-11 beta-PGF(2 alpha). High concentrations of LTE4 and PGD(2) metabolites were associated with lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in U-BIOARED participants and in adolescents with asthma. These type 2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study and were found to be as sensitive to detect T2 inflammation as the established biomarkers. Conclusions: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new noninvasive approach for molecular phenotyping of adult an

Published
2021
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16. Type 2-low asthma phenotypes by integration of sputum transcriptomics and serum proteomics

Author

U-BIOPRED Project, Team, Zounemat Kermani, Nazanin, Saqi, Mansoor, Agapow, Paul, Pavlidis, Stelios, Kuo, Chihhsi, Tan, Kai Sen, Mumby, Sharon, Sun, Kai, Loza, Matthew, Baribaud, Frederic, Sousa, Ana R., Riley, John, Wheelock, Asa M., Wheelock, Craig E., De Meulder, Bertrand, Schofield, Jim, Sánchez-Ovando, Stephany, Simpson, Jodie Louise, Baines, Katherine Joanne, Wark, Peter A., Auffray, Charles, Dahlen, Sven-Erik, Sterk, Peter J., Djukanovic, Ratko, Adcock, Ian M., Guo, Yike, Chung, Kian Fan, U-BIOPRED Project, Team, Zounemat Kermani, Nazanin, Saqi, Mansoor, Agapow, Paul, Pavlidis, Stelios, Kuo, Chihhsi, Tan, Kai Sen, Mumby, Sharon, Sun, Kai, Loza, Matthew, Baribaud, Frederic, Sousa, Ana R., Riley, John, Wheelock, Asa M., Wheelock, Craig E., De Meulder, Bertrand, Schofield, Jim, Sánchez-Ovando, Stephany, Simpson, Jodie Louise, Baines, Katherine Joanne, Wark, Peter A., Auffray, Charles, Dahlen, Sven-Erik, Sterk, Peter J., Djukanovic, Ratko, Adcock, Ian M., Guo, Yike, and Chung, Kian Fan

Published
2021

17. Isolation of rodent airway epithelial cell proteins facilitates in vivo proteomics studies of lung toxicity

Author

Wheelock, Asa M., Zhang, Lu, Tran, Mai-Uyen, Morin, Dexter, Penn, Sharron, Buckpitt, Alan R., and Plopper, Charles G.

Subjects
Electrophoresis -- Research, Biological sciences
Abstract

Recent developments in genomics, proteomics, and metaholomics hold substantial promise for understanding cellular responses to toxicants. Gene expression profiling is now considered standard procedure, but numerous publications reporting a lack of correlation between mRNA and protein expression emphasize the importance of conducting parallel proteomics studies. The cellular complexity of the lung presents great challenges for in vivo proteomics, and improved isolation methods for proteins from specific lung cell phenotypes are required. To address this issue, we have developed a novel method for isolation of rodent airway epithelial cell proteins that facilitates in vivo proteomics studies of two target-cell phenotypes of the lung, Clara cells and ciliated cells. The airway epithelial cell proteins are reproducibly solubilized, leaving the underlying basement membrane and smooth muscle intact as shown by histopathological analyses. The method yields epithelial cell-specific proteins in fivefold higher concentrations and reduces the yield of nonepithelial cell proteins 13-fold compared with homogenates from microdissected airways. In addition, 36% more protein spots were detectable by two-dimensional gel electrophoresis. two-dimensional gel electrophoresis; cytochrome P-450 monooxygenase; actin; airway epithelium; proteomics

Published
2004

21. Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, Zuba-Surma, Ewa K, dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, Urology, Pathology, Medical Oncology, Immunité et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University School of Medicine [Baltimore], Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department for Molecular Biology and Nanobiotechnology, National Institute of chemitry, Slovenia, Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Molecular Biotechnology Center, Università degli studi di Torino = University of Turin (UNITO), Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Centre for Sustainable Tropical Fisheries and Aquaculture, James Cook University (JCU), Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], Departamento de Ciências Biológicas, Universidade do Porto = University of Porto, Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), Universiteit Gent = Ghent University [Belgium] (UGENT), Department of Medical and Surgical Sciences for Children and Adults [Modena, Italy] (Laboratory of Cellular Therapy), Università degli Studi di Modena e Reggio Emilia (UNIMORE), Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Center for Cooperative Research in Biosciences (CIC bioGUNE), Partner site Munich, German Centre for Infection Research (DZIF), Institute for Transfusion Medicine, University Hospital Essen, Universität Duisburg-Essen [Essen], Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Psychiatry, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Bacteriology and Immunology [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Dalhousie University [Halifax], Department of Biology, Molecular Cell Biology, University of Mainz, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg (GU), Universidad de Alicante, École supérieure du professorat et de l'éducation - Académie de Créteil (UPEC ESPE Créteil), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of Antwerp (UA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Research Institute, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Veterinary Disease Biology [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Biologie et Pathologie du Neurone (Brain-C), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics, American University, University of Pretoria [South Africa], Ecole des Ingénieurs de la Ville de Paris (EIVP), Universitat Pompeu Fabra [Barcelona] (UPF), Instituto de Investigaciones Biomedicas, Universidad Nacional Autónoma de México (UNAM), Istituto Ortopedico Rizzoli, Department of Molecular Therapeutics, The Scripps Research Institute, Laboratoire d'Informatique de Grenoble (LIG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular Research Center, Massachusetts General Hospital [Boston], University Medical Center [Utrecht], University of Toronto, Fiocruz Minas - René Rachou Research Center / Instituto René Rachou [Belo Horizonte, Brésil], Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Federal University of Sao Paulo (Unifesp), Functional Genomics / Genómica Funcional [Montevideo], Institut Pasteur de Montevideo, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università degli Studi di Perugia (UNIPG), Hospital Santa Cristina Instituto de Investigación Sanitaria Princesa C, Unidad de Investigación, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, University of California [San Francisco] (UCSF), University of California-University of California, University of Vermont [Burlington], Peking University [Beijing], Shandong Agricultural University (SDAU), State Key Laboratory of Quality Research in Chinese Medicine Taipa, Macau SAR, (Institute of Chinese Medical Sciences), Human Genetics, Universität Ulm - Ulm University [Ulm, Allemagne], INSERM, Institut Curie, INCa [INCA-11548], French National Research Agency [ANR-10-IDEX-0001-02 PSL*, ANR-11-LABX-0043], SIDACTION [17-1-AAE-1138], Fondation ARC [PGA1 RF20180206962, PJA 20171206453], NIDA [DA040385, DA047807], Ministry of Education, NIA [AG057430], NIMH [MH118164], Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University (UGENT), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Biotechnology and Biological Sciences Research Council (BBSRC)-Aberystwyth University, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), The Scripps Research Institute [La Jolla, San Diego], Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Università degli Studi di Perugia = University of Perugia (UNIPG), Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), ANR-17-CE09-0025,MADNESS,Une approche microfluidique générique pour la qualification des nanoparticules biologiques(2017), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, Laboratory Specialized Diagnostics & Research, Radiotherapie, RS: GROW - R2 - Basic and Translational Cancer Biology, Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Università degli studi di Torino (UNITO), Universidade do Porto, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Toronto [Canada], Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade do Porto [Porto], Ghent University [Belgium] (UGENT), FEMTO-ST Institute, Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Franche-Comté (UFC)-CNRS : UMR6174, Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Johannes Gutenberg - University of Mainz (JGU), Université Catholique de Louvain (UCL), Universitat Pompeu Fabra [Barcelona], Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire Réactions et Génie des Procédés (LRGP), Fiocruz Minas - René Rachou Research Center / Instituto René Rachou, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Functional Genomics Unit, Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Vermont College of Medicine [Burlington, VT, USA], Extracellular Vesicles, Molecular and Integrative Biosciences Research Programme, Thery, C., Witwer, K. W., Aikawa, E., Alcaraz, M. J., Anderson, J. D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., Atkin-Smith, G. K., Ayre, D. C., Bach, J. -M., Bachurski, D., Baharvand, H., Balaj, L., Baldacchino, S., Bauer, N. N., Baxter, A. A., Bebawy, M., Beckham, C., Bedina Zavec, A., Benmoussa, A., Berardi, A. C., Bergese, P., Bielska, E., Blenkiron, C., Bobis-Wozowicz, S., Boilard, E., Boireau, W., Bongiovanni, A., Borras, F. E., Bosch, S., Boulanger, C. M., Breakefield, X., Breglio, A. M., Brennan, M. A., Brigstock, D. R., Brisson, A., Broekman, M. L. D., Bromberg, J. F., Bryl-Gorecka, P., Buch, S., Buck, A. H., Burger, D., Busatto, S., Buschmann, D., Bussolati, B., Buzas, E. I., Byrd, J. B., Camussi, G., Carter, D. R. F., Caruso, S., Chamley, L. W., Chang, Y. -T., Chaudhuri, A. D., Chen, C., Chen, S., Cheng, L., Chin, A. R., Clayton, A., Clerici, S. P., Cocks, A., Cocucci, E., Coffey, R. J., Cordeiro-da-Silva, A., Couch, Y., Coumans, F. A. W., Coyle, B., Crescitelli, R., Criado, M. F., D'Souza-Schorey, C., Das, S., de Candia, P., De Santana, E. F., De Wever, O., del Portillo, H. A., Demaret, T., Deville, S., Devitt, A., Dhondt, B., Di Vizio, D., Dieterich, L. C., Dolo, V., Dominguez Rubio, A. P., Dominici, M., Dourado, M. R., Driedonks, T. A. P., Duarte, F. V., Duncan, H. M., Eichenberger, R. M., Ekstrom, K., EL Andaloussi, S., Elie-Caille, C., Erdbrugger, U., Falcon-Perez, J. M., Fatima, F., Fish, J. E., Flores-Bellver, M., Forsonits, A., Frelet-Barrand, A., Fricke, F., Fuhrmann, G., Gabrielsson, S., Gamez-Valero, A., Gardiner, C., Gartner, K., Gaudin, R., Gho, Y. S., Giebel, B., Gilbert, C., Gimona, M., Giusti, I., Goberdhan, D. C. I., Gorgens, A., Gorski, S. M., Greening, D. W., Gross, J. C., Gualerzi, A., Gupta, G. N., Gustafson, D., Handberg, A., Haraszti, R. A., Harrison, P., Hegyesi, H., Hendrix, A., Hill, A. F., Hochberg, F. H., Hoffmann, K. F., Holder, B., Holthofer, H., Hosseinkhani, B., Hu, G., Huang, Y., Huber, V., Hunt, S., Ibrahim, A. G. -E., Ikezu, T., Inal, J. M., Isin, M., Ivanova, A., Jackson, H. K., Jacobsen, S., Jay, S. M., Jayachandran, M., Jenster, G., Jiang, L., Johnson, S. M., Jones, J. C., Jong, A., Jovanovic-Talisman, T., Jung, S., Kalluri, R., Kano, S. -I., Kaur, S., Kawamura, Y., Keller, E. T., Khamari, D., Khomyakova, E., Khvorova, A., Kierulf, P., Kim, K. P., Kislinger, T., Klingeborn, M., Klinke, D. J., Kornek, M., Kosanovic, M. M., Kovacs, A. F., Kramer-Albers, E. -M., Krasemann, S., Krause, M., Kurochkin, I. V., Kusuma, G. D., Kuypers, S., Laitinen, S., Langevin, S. M., Languino, L. R., Lannigan, J., Lasser, C., Laurent, L. C., Lavieu, G., Lazaro-Ibanez, E., Le Lay, S., Lee, M. -S., Lee, Y. X. F., Lemos, D. S., Lenassi, M., Leszczynska, A., Li, I. T. S., Liao, K., Libregts, S. F., Ligeti, E., Lim, R., Lim, S. K., Line, A., Linnemannstons, K., Llorente, A., Lombard, C. A., Lorenowicz, M. J., Lorincz, A. M., Lotvall, J., Lovett, J., Lowry, M. C., Loyer, X., Lu, Q., Lukomska, B., Lunavat, T. R., Maas, S. L. N., Malhi, H., Marcilla, A., Mariani, J., Mariscal, J., Martens-Uzunova, E. S., Martin-Jaular, L., Martinez, M. C., Martins, V. R., Mathieu, M., Mathivanan, S., Maugeri, M., Mcginnis, L. K., Mcvey, M. J., Meckes, D. G., Meehan, K. L., Mertens, I., Minciacchi, V. R., Moller, A., Moller Jorgensen, M., Morales-Kastresana, A., Morhayim, J., Mullier, F., Muraca, M., Musante, L., Mussack, V., Muth, D. C., Myburgh, K. H., Najrana, T., Nawaz, M., Nazarenko, I., Nejsum, P., Neri, C., Neri, T., Nieuwland, R., Nimrichter, L., Nolan, J. P., Nolte-'t Hoen, E. N. M., Noren Hooten, N., O'Driscoll, L., O'Grady, T., O'Loghlen, A., Ochiya, T., Olivier, M., Ortiz, A., Ortiz, L. A., Osteikoetxea, X., Ostegaard, O., Ostrowski, M., Park, J., Pegtel, D. M., Peinado, H., Perut, F., Pfaffl, M. W., Phinney, D. G., Pieters, B. C. H., Pink, R. C., Pisetsky, D. S., Pogge von Strandmann, E., Polakovicova, I., Poon, I. K. H., Powell, B. H., Prada, I., Pulliam, L., Quesenberry, P., Radeghieri, A., Raffai, R. L., Raimondo, S., Rak, J., Ramirez, M. I., Raposo, G., Rayyan, M. S., Regev-Rudzki, N., Ricklefs, F. L., Robbins, P. D., Roberts, D. D., Rodrigues, S. C., Rohde, E., Rome, S., Rouschop, K. M. A., Rughetti, A., Russell, A. E., Saa, P., Sahoo, S., Salas-Huenuleo, E., Sanchez, C., Saugstad, J. A., Saul, M. J., Schiffelers, R. M., Schneider, R., Schoyen, T. H., Scott, A., Shahaj, E., Sharma, S., Shatnyeva, O., Shekari, F., Shelke, G. V., Shetty, A. K., Shiba, K., Siljander, P. R. -M., Silva, A. M., Skowronek, A., Snyder, O. L., Soares, R. P., Sodar, B. W., Soekmadji, C., Sotillo, J., Stahl, P. D., Stoorvogel, W., Stott, S. L., Strasser, E. F., Swift, S., Tahara, H., Tewari, M., Timms, K., Tiwari, S., Tixeira, R., Tkach, M., Toh, W. S., Tomasini, R., Torrecilhas, A. C., Tosar, J. P., Toxavidis, V., Urbanelli, L., Vader, P., van Balkom, B. W. M., van der Grein, S. G., Van Deun, J., van Herwijnen, M. J. C., Van Keuren-Jensen, K., van Niel, G., van Royen, M. E., van Wijnen, A. J., Vasconcelos, M. H., Vechetti, I. J., Veit, T. D., Vella, L. J., Velot, E., Verweij, F. J., Vestad, B., Vinas, J. L., Visnovitz, T., Vukman, K. V., Wahlgren, J., Watson, D. C., Wauben, M. H. M., Weaver, A., Webber, J. P., Weber, V., Wehman, A. M., Weiss, D. J., Welsh, J. A., Wendt, S., Wheelock, A. M., Wiener, Z., Witte, L., Wolfram, J., Xagorari, A., Xander, P., Xu, J., Yan, X., Yanez-Mo, M., Yin, H., Yuana, Y., Zappulli, V., Zarubova, J., Zekas, V., Zhang, J. -Y., Zhao, Z., Zheng, L., Zheutlin, A. R., Zickler, A. M., Zimmermann, P., Zivkovic, A. M., Zocco, D., Zuba-Surma, E. K., dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Neuroinfection & -inflammation, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms

Subjects
ectosome, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, Histology, Cell Biology, [SDV]Life Sciences [q-bio], size-exclusion, Medicine and Health Sciences, CELL-DERIVED MICROPARTICLES, FIELD-FLOW FRACTIONATION, requirements, circulating, ComputingMilieux_MISCELLANEOUS, Manchester Cancer Research Centre, lcsh:Cytology, PROSTATE-CANCER, microparticle, Cell interaction, microvesicle, chromatography, Position Paper, guideline, Life Sciences & Biomedicine, ectosomes, exosomes, extracellular vesicles, guidelines, microparticles, microvesicles, minimal information requirements, reproducibility, rigor, standardization, MEMBRANE-VESICLES, FETAL BOVINE, Ectosomes, Exosomes, Extracellular Vesicles, Guidelines, Microparticles, Microvesicles, Minimal Information Requirements, Reproducibility, Rigor, Standardization, CIRCULATING MICROPARTICLES, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ddc:570, exosome, SURFACE-PLASMON RESONANCE, ddc:610, lcsh:QH573-671, Biology, Interacció cel·lular, Science & Technology, ResearchInstitutes_Networks_Beacons/mcrc, Cell membranes, HUMAN URINARY EXOSOMES, PREANALYTICAL PARAMETERS, minimal information requirement, SIZE-EXCLUSION CHROMATOGRAPHY, 1182 Biochemistry, cell and molecular biology, extracellular vesicle, Human medicine, Membranes cel·lulars
Abstract

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Published
2018
Full Text
View/download PDF

22. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, Witwer, Kenneth W., Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D., Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkiin-Smith, Georgia K., Ayre, D. Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N., Baxter, Amy A., Bebawy, Mary, Beckham, Carla, Zavec, Apolonija Bedina, Benmoussa, Abderrahim, Berardi, Anna C., Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E., Bosch, Steffi, Boulanger, Chantal M., Breakefield, Xandra, Breglio, Andrew M., Brennan, Meadhbh Á, Brigstock, David R., Brisson, Alain, Broekman, Marike L.D., Bromberg, Jacqueline F., Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H., Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I., Byrd, James Bryan, Camussi, Giovanni, Carter, David R.F., Caruso, Sarah, Chamley, Lawrence W., Chang, Yu-Ting, Chen, Chichen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R., Clayton, Aled, Clerici, Stefano P., Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J., Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank A.W., Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D’ Souza-Schorey, Crislyn, Das, Saumya, Chaudhuri, Amrita Datta, de Candia, Paola, De Santana Junior, Eliezer F., De Wever, Olivier, del Portillo, Hernando A., Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C., Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R., Driedonks, Tom A.P, Duarte, Filipe V., Duncan, Heather M., Eichenberger, Ramon M., Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M., Fatima, Farah, Fish, Jason E., Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah C.I., Görgens, André, Gorski, Sharon M., Greening, David W., Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N., Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A., Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F., Hochberg, Fred H., Hoffmann, Karl F., Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M., Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K., Jacobsen, Soren, Jay, Steven M., Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M., Jones, Jennifer C., Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T., Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke II, David J., Kornek, Miroslaw, Kosanović, Maja M., Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V., Kusuma, Gina D., Kuypers, Sören, Laitinen, Saara, Langevin, Scott M., Languino, Lucia R., Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C., Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Lay, Soazig Le, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S., Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac T.S., Liao, Ke, Libregts, Sten F., Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A., Lorenowicz, Magdalena J., Lörincz, Ákos M., Lötvall, Jan, Lovett, Jason, Lowry, Michelle C., Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R., Maas, Sybren L.N., Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S., Martin-Jaular, Lorena, Martinez, M. Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K., McVey, Mark J., Meckes, Jr., David G., Meehan, Katie L., Mertens, Inge, Minciacchi, Valentina R., Möller, Andreas, Jørgensen, Malene Møller, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C., Myburgh, Kathryn H., Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P., Nolte-’ t Hoen, Esther N.M., Hooten, Nicole Noren, O’Driscoll, Lorraine, O’Grady, Tina, O’Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A., Osteikoetxea, Xabier, Ostegaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D. Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W., Phinney, Donald G., Pieters, Bartijn C.H., Pink, Ryan C., Pisetsky, David S., von Strandmann, Elke Pogge, Polakovicova, Iva, Poon, Ivan K.H., Powell, Bonita H., Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L., Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I., Raposo, Graça, Rayyan, Morsi S., Regev-Rudzki, Neta, Ricklefs, Fran L., Robbins, Paul D., Roberts, David D., Rodrigues, Silvia C., Rohde, Eva, Rome, Sophie, Rouschop, Kasper M.A., Rughetti, Aurelia, Russell, Ashley E., Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A., Saul, Meike J., Schiffelers, Raymond M., Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K., Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M., Skowronek, Agata, Snyder II, Orman L., Soares, Rodrigo Pedro, Sódar, Barbara W., Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D., Stoorvogel, Willem, Stott, Shannon L., Strasser, Erwin F., Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas W.M., van der Grein, Susanne G., Van Deun, Jan, van Herwijnen, Martijn J.C., van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E., van Wijnen, Andre J., Vasconcelos, M. Helena, Vechetti Jr., Ivan J., Veit, Tiago D., Vella, Laura J., Velot, Émilie, Verweij, Frederik J., Vestad, Beate, Viñas, Jose L., Visnovitz, Tamás, Vukman, Krisztina V., Wahlgren, Jessica, Watson, Dionysios C., Wauben, Marca H.M., Weaver, Alissa, Webber, Jason P., Weber, Viktoria, Wehman, Ann M., Weiss, Daniel J., Welsh, Joshua A., Wendt, Sebastian, Wheelock, Asa M., Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R., Zickler, Antje M., Zimmermann, Pascale, Zivkovic, Angela M., Zocco, Davide, Zuba-Surma, Ewa K., Théry, Clotilde, Witwer, Kenneth W., Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D., Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkiin-Smith, Georgia K., Ayre, D. Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N., Baxter, Amy A., Bebawy, Mary, Beckham, Carla, Zavec, Apolonija Bedina, Benmoussa, Abderrahim, Berardi, Anna C., Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E., Bosch, Steffi, Boulanger, Chantal M., Breakefield, Xandra, Breglio, Andrew M., Brennan, Meadhbh Á, Brigstock, David R., Brisson, Alain, Broekman, Marike L.D., Bromberg, Jacqueline F., Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H., Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I., Byrd, James Bryan, Camussi, Giovanni, Carter, David R.F., Caruso, Sarah, Chamley, Lawrence W., Chang, Yu-Ting, Chen, Chichen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R., Clayton, Aled, Clerici, Stefano P., Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J., Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank A.W., Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D’ Souza-Schorey, Crislyn, Das, Saumya, Chaudhuri, Amrita Datta, de Candia, Paola, De Santana Junior, Eliezer F., De Wever, Olivier, del Portillo, Hernando A., Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C., Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R., Driedonks, Tom A.P, Duarte, Filipe V., Duncan, Heather M., Eichenberger, Ramon M., Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M., Fatima, Farah, Fish, Jason E., Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah C.I., Görgens, André, Gorski, Sharon M., Greening, David W., Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N., Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A., Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F., Hochberg, Fred H., Hoffmann, Karl F., Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M., Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K., Jacobsen, Soren, Jay, Steven M., Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M., Jones, Jennifer C., Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T., Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke II, David J., Kornek, Miroslaw, Kosanović, Maja M., Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V., Kusuma, Gina D., Kuypers, Sören, Laitinen, Saara, Langevin, Scott M., Languino, Lucia R., Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C., Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Lay, Soazig Le, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S., Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac T.S., Liao, Ke, Libregts, Sten F., Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A., Lorenowicz, Magdalena J., Lörincz, Ákos M., Lötvall, Jan, Lovett, Jason, Lowry, Michelle C., Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R., Maas, Sybren L.N., Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S., Martin-Jaular, Lorena, Martinez, M. Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K., McVey, Mark J., Meckes, Jr., David G., Meehan, Katie L., Mertens, Inge, Minciacchi, Valentina R., Möller, Andreas, Jørgensen, Malene Møller, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C., Myburgh, Kathryn H., Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P., Nolte-’ t Hoen, Esther N.M., Hooten, Nicole Noren, O’Driscoll, Lorraine, O’Grady, Tina, O’Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A., Osteikoetxea, Xabier, Ostegaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D. Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W., Phinney, Donald G., Pieters, Bartijn C.H., Pink, Ryan C., Pisetsky, David S., von Strandmann, Elke Pogge, Polakovicova, Iva, Poon, Ivan K.H., Powell, Bonita H., Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L., Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I., Raposo, Graça, Rayyan, Morsi S., Regev-Rudzki, Neta, Ricklefs, Fran L., Robbins, Paul D., Roberts, David D., Rodrigues, Silvia C., Rohde, Eva, Rome, Sophie, Rouschop, Kasper M.A., Rughetti, Aurelia, Russell, Ashley E., Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A., Saul, Meike J., Schiffelers, Raymond M., Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K., Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M., Skowronek, Agata, Snyder II, Orman L., Soares, Rodrigo Pedro, Sódar, Barbara W., Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D., Stoorvogel, Willem, Stott, Shannon L., Strasser, Erwin F., Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas W.M., van der Grein, Susanne G., Van Deun, Jan, van Herwijnen, Martijn J.C., van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E., van Wijnen, Andre J., Vasconcelos, M. Helena, Vechetti Jr., Ivan J., Veit, Tiago D., Vella, Laura J., Velot, Émilie, Verweij, Frederik J., Vestad, Beate, Viñas, Jose L., Visnovitz, Tamás, Vukman, Krisztina V., Wahlgren, Jessica, Watson, Dionysios C., Wauben, Marca H.M., Weaver, Alissa, Webber, Jason P., Weber, Viktoria, Wehman, Ann M., Weiss, Daniel J., Welsh, Joshua A., Wendt, Sebastian, Wheelock, Asa M., Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R., Zickler, Antje M., Zimmermann, Pascale, Zivkovic, Angela M., Zocco, Davide, and Zuba-Surma, Ewa K.

Abstract

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points. © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.

Published
2019

23. Type 2‐low asthma phenotypes by integration of sputum transcriptomics and serum proteomics.

Author

Zounemat Kermani, Nazanin, Saqi, Mansoor, Agapow, Paul, Pavlidis, Stelios, Kuo, Chihhsi, Tan, Kai Sen, Mumby, Sharon, Sun, Kai, Loza, Matthew, Baribaud, Frederic, Sousa, Ana R., Riley, John, Wheelock, Asa M., Wheelock, Craig E., De Meulder, Bertrand, Schofield, Jim, Sánchez‐Ovando, Stephany, Simpson, Jodie Louise, Baines, Katherine Joanne, and Wark, Peter A.

Subjects
PROTEOMICS, SPUTUM, ASTHMA, SERUM, TRANSCRIPTOMES, PHENOTYPES
Abstract

Keywords: asthma; bioinformatics; endotypes; precision medicine; systems biology EN asthma bioinformatics endotypes precision medicine systems biology 380 383 4 01/09/21 20210101 NES 210101 I To the Editor, i Asthma is a complex heterogeneous disease that presents with varying degrees of severity. We identified four optimal clusters (TAC*1, TAC*2, TAC*3a and TAC*3b) (Figure S3), in agreement with our previous clustering1 where TAC*3a and TAC*3b were combined. Asthma, bioinformatics, endotypes, precision medicine, systems biology. [Extracted from the article]

Published
2021
Full Text
View/download PDF

24. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, primary, Witwer, Kenneth W, additional, Aikawa, Elena, additional, Alcaraz, Maria Jose, additional, Anderson, Johnathon D, additional, Andriantsitohaina, Ramaroson, additional, Antoniou, Anna, additional, Arab, Tanina, additional, Archer, Fabienne, additional, Atkin-Smith, Georgia K, additional, Ayre, D Craig, additional, Bach, Jean-Marie, additional, Bachurski, Daniel, additional, Baharvand, Hossein, additional, Balaj, Leonora, additional, Baldacchino, Shawn, additional, Bauer, Natalie N, additional, Baxter, Amy A, additional, Bebawy, Mary, additional, Beckham, Carla, additional, Bedina Zavec, Apolonija, additional, Benmoussa, Abderrahim, additional, Berardi, Anna C, additional, Bergese, Paolo, additional, Bielska, Ewa, additional, Blenkiron, Cherie, additional, Bobis-Wozowicz, Sylwia, additional, Boilard, Eric, additional, Boireau, Wilfrid, additional, Bongiovanni, Antonella, additional, Borràs, Francesc E, additional, Bosch, Steffi, additional, Boulanger, Chantal M, additional, Breakefield, Xandra, additional, Breglio, Andrew M, additional, Brennan, Meadhbh Á, additional, Brigstock, David R, additional, Brisson, Alain, additional, Broekman, Marike LD, additional, Bromberg, Jacqueline F, additional, Bryl-Górecka, Paulina, additional, Buch, Shilpa, additional, Buck, Amy H, additional, Burger, Dylan, additional, Busatto, Sara, additional, Buschmann, Dominik, additional, Bussolati, Benedetta, additional, Buzás, Edit I, additional, Byrd, James Bryan, additional, Camussi, Giovanni, additional, Carter, David RF, additional, Caruso, Sarah, additional, Chamley, Lawrence W, additional, Chang, Yu-Ting, additional, Chen, Chihchen, additional, Chen, Shuai, additional, Cheng, Lesley, additional, Chin, Andrew R, additional, Clayton, Aled, additional, Clerici, Stefano P, additional, Cocks, Alex, additional, Cocucci, Emanuele, additional, Coffey, Robert J, additional, Cordeiro-da-Silva, Anabela, additional, Couch, Yvonne, additional, Coumans, Frank AW, additional, Coyle, Beth, additional, Crescitelli, Rossella, additional, Criado, Miria Ferreira, additional, D’Souza-Schorey, Crislyn, additional, Das, Saumya, additional, Datta Chaudhuri, Amrita, additional, de Candia, Paola, additional, De Santana, Eliezer F, additional, De Wever, Olivier, additional, del Portillo, Hernando A, additional, Demaret, Tanguy, additional, Deville, Sarah, additional, Devitt, Andrew, additional, Dhondt, Bert, additional, Di Vizio, Dolores, additional, Dieterich, Lothar C, additional, Dolo, Vincenza, additional, Dominguez Rubio, Ana Paula, additional, Dominici, Massimo, additional, Dourado, Mauricio R, additional, Driedonks, Tom AP, additional, Duarte, Filipe V, additional, Duncan, Heather M, additional, Eichenberger, Ramon M, additional, Ekström, Karin, additional, EL Andaloussi, Samir, additional, Elie-Caille, Celine, additional, Erdbrügger, Uta, additional, Falcón-Pérez, Juan M, additional, Fatima, Farah, additional, Fish, Jason E, additional, Flores-Bellver, Miguel, additional, Försönits, András, additional, Frelet-Barrand, Annie, additional, Fricke, Fabia, additional, Fuhrmann, Gregor, additional, Gabrielsson, Susanne, additional, Gámez-Valero, Ana, additional, Gardiner, Chris, additional, Gärtner, Kathrin, additional, Gaudin, Raphael, additional, Gho, Yong Song, additional, Giebel, Bernd, additional, Gilbert, Caroline, additional, Gimona, Mario, additional, Giusti, Ilaria, additional, Goberdhan, Deborah CI, additional, Görgens, André, additional, Gorski, Sharon M, additional, Greening, David W, additional, Gross, Julia Christina, additional, Gualerzi, Alice, additional, Gupta, Gopal N, additional, Gustafson, Dakota, additional, Handberg, Aase, additional, Haraszti, Reka A, additional, Harrison, Paul, additional, Hegyesi, Hargita, additional, Hendrix, An, additional, Hill, Andrew F, additional, Hochberg, Fred H, additional, Hoffmann, Karl F, additional, Holder, Beth, additional, Holthofer, Harry, additional, Hosseinkhani, Baharak, additional, Hu, Guoku, additional, Huang, Yiyao, additional, Huber, Veronica, additional, Hunt, Stuart, additional, Ibrahim, Ahmed Gamal-Eldin, additional, Ikezu, Tsuneya, additional, Inal, Jameel M, additional, Isin, Mustafa, additional, Ivanova, Alena, additional, Jackson, Hannah K, additional, Jacobsen, Soren, additional, Jay, Steven M, additional, Jayachandran, Muthuvel, additional, Jenster, Guido, additional, Jiang, Lanzhou, additional, Johnson, Suzanne M, additional, Jones, Jennifer C, additional, Jong, Ambrose, additional, Jovanovic-Talisman, Tijana, additional, Jung, Stephanie, additional, Kalluri, Raghu, additional, Kano, Shin-ichi, additional, Kaur, Sukhbir, additional, Kawamura, Yumi, additional, Keller, Evan T, additional, Khamari, Delaram, additional, Khomyakova, Elena, additional, Khvorova, Anastasia, additional, Kierulf, Peter, additional, Kim, Kwang Pyo, additional, Kislinger, Thomas, additional, Klingeborn, Mikael, additional, Klinke, David J, additional, Kornek, Miroslaw, additional, Kosanović, Maja M, additional, Kovács, Árpád Ferenc, additional, Krämer-Albers, Eva-Maria, additional, Krasemann, Susanne, additional, Krause, Mirja, additional, Kurochkin, Igor V, additional, Kusuma, Gina D, additional, Kuypers, Sören, additional, Laitinen, Saara, additional, Langevin, Scott M, additional, Languino, Lucia R, additional, Lannigan, Joanne, additional, Lässer, Cecilia, additional, Laurent, Louise C, additional, Lavieu, Gregory, additional, Lázaro-Ibáñez, Elisa, additional, Le Lay, Soazig, additional, Lee, Myung-Shin, additional, Lee, Yi Xin Fiona, additional, Lemos, Debora S, additional, Lenassi, Metka, additional, Leszczynska, Aleksandra, additional, Li, Isaac TS, additional, Liao, Ke, additional, Libregts, Sten F, additional, Ligeti, Erzsebet, additional, Lim, Rebecca, additional, Lim, Sai Kiang, additional, Linē, Aija, additional, Linnemannstöns, Karen, additional, Llorente, Alicia, additional, Lombard, Catherine A, additional, Lorenowicz, Magdalena J, additional, Lörincz, Ákos M, additional, Lötvall, Jan, additional, Lovett, Jason, additional, Lowry, Michelle C, additional, Loyer, Xavier, additional, Lu, Quan, additional, Lukomska, Barbara, additional, Lunavat, Taral R, additional, Maas, Sybren LN, additional, Malhi, Harmeet, additional, Marcilla, Antonio, additional, Mariani, Jacopo, additional, Mariscal, Javier, additional, Martens-Uzunova, Elena S, additional, Martin-Jaular, Lorena, additional, Martinez, M Carmen, additional, Martins, Vilma Regina, additional, Mathieu, Mathilde, additional, Mathivanan, Suresh, additional, Maugeri, Marco, additional, McGinnis, Lynda K, additional, McVey, Mark J, additional, Meckes, David G, additional, Meehan, Katie L, additional, Mertens, Inge, additional, Minciacchi, Valentina R, additional, Möller, Andreas, additional, Møller Jørgensen, Malene, additional, Morales-Kastresana, Aizea, additional, Morhayim, Jess, additional, Mullier, François, additional, Muraca, Maurizio, additional, Musante, Luca, additional, Mussack, Veronika, additional, Muth, Dillon C, additional, Myburgh, Kathryn H, additional, Najrana, Tanbir, additional, Nawaz, Muhammad, additional, Nazarenko, Irina, additional, Nejsum, Peter, additional, Neri, Christian, additional, Neri, Tommaso, additional, Nieuwland, Rienk, additional, Nimrichter, Leonardo, additional, Nolan, John P, additional, Nolte-’t Hoen, Esther NM, additional, Noren Hooten, Nicole, additional, O’Driscoll, Lorraine, additional, O’Grady, Tina, additional, O’Loghlen, Ana, additional, Ochiya, Takahiro, additional, Olivier, Martin, additional, Ortiz, Alberto, additional, Ortiz, Luis A, additional, Osteikoetxea, Xabier, additional, Østergaard, Ole, additional, Ostrowski, Matias, additional, Park, Jaesung, additional, Pegtel, D. Michiel, additional, Peinado, Hector, additional, Perut, Francesca, additional, Pfaffl, Michael W, additional, Phinney, Donald G, additional, Pieters, Bartijn CH, additional, Pink, Ryan C, additional, Pisetsky, David S, additional, Pogge von Strandmann, Elke, additional, Polakovicova, Iva, additional, Poon, Ivan KH, additional, Powell, Bonita H, additional, Prada, Ilaria, additional, Pulliam, Lynn, additional, Quesenberry, Peter, additional, Radeghieri, Annalisa, additional, Raffai, Robert L, additional, Raimondo, Stefania, additional, Rak, Janusz, additional, Ramirez, Marcel I, additional, Raposo, Graça, additional, Rayyan, Morsi S, additional, Regev-Rudzki, Neta, additional, Ricklefs, Franz L, additional, Robbins, Paul D, additional, Roberts, David D, additional, Rodrigues, Silvia C, additional, Rohde, Eva, additional, Rome, Sophie, additional, Rouschop, Kasper MA, additional, Rughetti, Aurelia, additional, Russell, Ashley E, additional, Saá, Paula, additional, Sahoo, Susmita, additional, Salas-Huenuleo, Edison, additional, Sánchez, Catherine, additional, Saugstad, Julie A, additional, Saul, Meike J, additional, Schiffelers, Raymond M, additional, Schneider, Raphael, additional, Schøyen, Tine Hiorth, additional, Scott, Aaron, additional, Shahaj, Eriomina, additional, Sharma, Shivani, additional, Shatnyeva, Olga, additional, Shekari, Faezeh, additional, Shelke, Ganesh Vilas, additional, Shetty, Ashok K, additional, Shiba, Kiyotaka, additional, Siljander, Pia R-M, additional, Silva, Andreia M, additional, Skowronek, Agata, additional, Snyder, Orman L, additional, Soares, Rodrigo Pedro, additional, Sódar, Barbara W, additional, Soekmadji, Carolina, additional, Sotillo, Javier, additional, Stahl, Philip D, additional, Stoorvogel, Willem, additional, Stott, Shannon L, additional, Strasser, Erwin F, additional, Swift, Simon, additional, Tahara, Hidetoshi, additional, Tewari, Muneesh, additional, Timms, Kate, additional, Tiwari, Swasti, additional, Tixeira, Rochelle, additional, Tkach, Mercedes, additional, Toh, Wei Seong, additional, Tomasini, Richard, additional, Torrecilhas, Ana Claudia, additional, Tosar, Juan Pablo, additional, Toxavidis, Vasilis, additional, Urbanelli, Lorena, additional, Vader, Pieter, additional, van Balkom, Bas WM, additional, van der Grein, Susanne G, additional, Van Deun, Jan, additional, van Herwijnen, Martijn JC, additional, Van Keuren-Jensen, Kendall, additional, van Niel, Guillaume, additional, van Royen, Martin E, additional, van Wijnen, Andre J, additional, Vasconcelos, M Helena, additional, Vechetti, Ivan J, additional, Veit, Tiago D, additional, Vella, Laura J, additional, Velot, Émilie, additional, Verweij, Frederik J, additional, Vestad, Beate, additional, Viñas, Jose L, additional, Visnovitz, Tamás, additional, Vukman, Krisztina V, additional, Wahlgren, Jessica, additional, Watson, Dionysios C, additional, Wauben, Marca HM, additional, Weaver, Alissa, additional, Webber, Jason P, additional, Weber, Viktoria, additional, Wehman, Ann M, additional, Weiss, Daniel J, additional, Welsh, Joshua A, additional, Wendt, Sebastian, additional, Wheelock, Asa M, additional, Wiener, Zoltán, additional, Witte, Leonie, additional, Wolfram, Joy, additional, Xagorari, Angeliki, additional, Xander, Patricia, additional, Xu, Jing, additional, Yan, Xiaomei, additional, Yáñez-Mó, María, additional, Yin, Hang, additional, Yuana, Yuana, additional, Zappulli, Valentina, additional, Zarubova, Jana, additional, Žėkas, Vytautas, additional, Zhang, Jian-ye, additional, Zhao, Zezhou, additional, Zheng, Lei, additional, Zheutlin, Alexander R, additional, Zickler, Antje M, additional, Zimmermann, Pascale, additional, Zivkovic, Angela M, additional, Zocco, Davide, additional, and Zuba-Surma, Ewa K, additional

Published
2018
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25. Late Breaking Abstract - Elevated airway lymphocytes in adults born prematurely with a history of bronchopulmonary dysplasia

Author

Gao, Jing, primary, Um-Bergstrom, Petra, additional, Pourbazargan, Melvin, additional, Berggren-Brostrom, Eva, additional, Merikallio, Heta, additional, Kaarteenaho, Riitta, additional, Reinke, Stacey, additional, Wheelock, Craig E, additional, Melen, Erik, additional, Linden, Anders, additional, Wheelock, Asa M, additional, and Skold, C Magnus, additional

Published
2018
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26. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, Zuba-Surma, Ewa K, Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, and Zuba-Surma, Ewa K

Abstract

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Published
2018

27. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Author

dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, Zuba-Surma, Ewa K, dB&C I&I, LS Celbiologie-Algemeen, Celbiologie, Afd Pharmaceutics, Sub General Pharmaceutics, Sub Biomol.Mass Spect. and Proteomics, Afd Pharmacology, Théry, Clotilde, Witwer, Kenneth W, Aikawa, Elena, Alcaraz, Maria Jose, Anderson, Johnathon D, Andriantsitohaina, Ramaroson, Antoniou, Anna, Arab, Tanina, Archer, Fabienne, Atkin-Smith, Georgia K, Ayre, D Craig, Bach, Jean-Marie, Bachurski, Daniel, Baharvand, Hossein, Balaj, Leonora, Baldacchino, Shawn, Bauer, Natalie N, Baxter, Amy A, Bebawy, Mary, Beckham, Carla, Bedina Zavec, Apolonija, Benmoussa, Abderrahim, Berardi, Anna C, Bergese, Paolo, Bielska, Ewa, Blenkiron, Cherie, Bobis-Wozowicz, Sylwia, Boilard, Eric, Boireau, Wilfrid, Bongiovanni, Antonella, Borràs, Francesc E, Bosch, Steffi, Boulanger, Chantal M, Breakefield, Xandra, Breglio, Andrew M, Brennan, Meadhbh Á, Brigstock, David R, Brisson, Alain, Broekman, Marike Ld, Bromberg, Jacqueline F, Bryl-Górecka, Paulina, Buch, Shilpa, Buck, Amy H, Burger, Dylan, Busatto, Sara, Buschmann, Dominik, Bussolati, Benedetta, Buzás, Edit I, Byrd, James Bryan, Camussi, Giovanni, Carter, David Rf, Caruso, Sarah, Chamley, Lawrence W, Chang, Yu-Ting, Chen, Chihchen, Chen, Shuai, Cheng, Lesley, Chin, Andrew R, Clayton, Aled, Clerici, Stefano P, Cocks, Alex, Cocucci, Emanuele, Coffey, Robert J, Cordeiro-da-Silva, Anabela, Couch, Yvonne, Coumans, Frank Aw, Coyle, Beth, Crescitelli, Rossella, Criado, Miria Ferreira, D'Souza-Schorey, Crislyn, Das, Saumya, Datta Chaudhuri, Amrita, de Candia, Paola, De Santana, Eliezer F, De Wever, Olivier, Del Portillo, Hernando A, Demaret, Tanguy, Deville, Sarah, Devitt, Andrew, Dhondt, Bert, Di Vizio, Dolores, Dieterich, Lothar C, Dolo, Vincenza, Dominguez Rubio, Ana Paula, Dominici, Massimo, Dourado, Mauricio R, Driedonks, Tom Ap, Duarte, Filipe V, Duncan, Heather M, Eichenberger, Ramon M, Ekström, Karin, El Andaloussi, Samir, Elie-Caille, Celine, Erdbrügger, Uta, Falcón-Pérez, Juan M, Fatima, Farah, Fish, Jason E, Flores-Bellver, Miguel, Försönits, András, Frelet-Barrand, Annie, Fricke, Fabia, Fuhrmann, Gregor, Gabrielsson, Susanne, Gámez-Valero, Ana, Gardiner, Chris, Gärtner, Kathrin, Gaudin, Raphael, Gho, Yong Song, Giebel, Bernd, Gilbert, Caroline, Gimona, Mario, Giusti, Ilaria, Goberdhan, Deborah Ci, Görgens, André, Gorski, Sharon M, Greening, David W, Gross, Julia Christina, Gualerzi, Alice, Gupta, Gopal N, Gustafson, Dakota, Handberg, Aase, Haraszti, Reka A, Harrison, Paul, Hegyesi, Hargita, Hendrix, An, Hill, Andrew F, Hochberg, Fred H, Hoffmann, Karl F, Holder, Beth, Holthofer, Harry, Hosseinkhani, Baharak, Hu, Guoku, Huang, Yiyao, Huber, Veronica, Hunt, Stuart, Ibrahim, Ahmed Gamal-Eldin, Ikezu, Tsuneya, Inal, Jameel M, Isin, Mustafa, Ivanova, Alena, Jackson, Hannah K, Jacobsen, Soren, Jay, Steven M, Jayachandran, Muthuvel, Jenster, Guido, Jiang, Lanzhou, Johnson, Suzanne M, Jones, Jennifer C, Jong, Ambrose, Jovanovic-Talisman, Tijana, Jung, Stephanie, Kalluri, Raghu, Kano, Shin-Ichi, Kaur, Sukhbir, Kawamura, Yumi, Keller, Evan T, Khamari, Delaram, Khomyakova, Elena, Khvorova, Anastasia, Kierulf, Peter, Kim, Kwang Pyo, Kislinger, Thomas, Klingeborn, Mikael, Klinke, David J, Kornek, Miroslaw, Kosanović, Maja M, Kovács, Árpád Ferenc, Krämer-Albers, Eva-Maria, Krasemann, Susanne, Krause, Mirja, Kurochkin, Igor V, Kusuma, Gina D, Kuypers, Sören, Laitinen, Saara, Langevin, Scott M, Languino, Lucia R, Lannigan, Joanne, Lässer, Cecilia, Laurent, Louise C, Lavieu, Gregory, Lázaro-Ibáñez, Elisa, Le Lay, Soazig, Lee, Myung-Shin, Lee, Yi Xin Fiona, Lemos, Debora S, Lenassi, Metka, Leszczynska, Aleksandra, Li, Isaac Ts, Liao, Ke, Libregts, Sten F, Ligeti, Erzsebet, Lim, Rebecca, Lim, Sai Kiang, Linē, Aija, Linnemannstöns, Karen, Llorente, Alicia, Lombard, Catherine A, Lorenowicz, Magdalena J, Lörincz, Ákos M, Lötvall, Jan, Lovett, Jason, Lowry, Michelle C, Loyer, Xavier, Lu, Quan, Lukomska, Barbara, Lunavat, Taral R, Maas, Sybren Ln, Malhi, Harmeet, Marcilla, Antonio, Mariani, Jacopo, Mariscal, Javier, Martens-Uzunova, Elena S, Martin-Jaular, Lorena, Martinez, M Carmen, Martins, Vilma Regina, Mathieu, Mathilde, Mathivanan, Suresh, Maugeri, Marco, McGinnis, Lynda K, McVey, Mark J, Meckes, David G, Meehan, Katie L, Mertens, Inge, Minciacchi, Valentina R, Möller, Andreas, Møller Jørgensen, Malene, Morales-Kastresana, Aizea, Morhayim, Jess, Mullier, François, Muraca, Maurizio, Musante, Luca, Mussack, Veronika, Muth, Dillon C, Myburgh, Kathryn H, Najrana, Tanbir, Nawaz, Muhammad, Nazarenko, Irina, Nejsum, Peter, Neri, Christian, Neri, Tommaso, Nieuwland, Rienk, Nimrichter, Leonardo, Nolan, John P, Nolte-'t Hoen, Esther NM, Noren Hooten, Nicole, O'Driscoll, Lorraine, O'Grady, Tina, O'Loghlen, Ana, Ochiya, Takahiro, Olivier, Martin, Ortiz, Alberto, Ortiz, Luis A, Osteikoetxea, Xabier, Østergaard, Ole, Ostrowski, Matias, Park, Jaesung, Pegtel, D Michiel, Peinado, Hector, Perut, Francesca, Pfaffl, Michael W, Phinney, Donald G, Pieters, Bartijn Ch, Pink, Ryan C, Pisetsky, David S, Pogge von Strandmann, Elke, Polakovicova, Iva, Poon, Ivan Kh, Powell, Bonita H, Prada, Ilaria, Pulliam, Lynn, Quesenberry, Peter, Radeghieri, Annalisa, Raffai, Robert L, Raimondo, Stefania, Rak, Janusz, Ramirez, Marcel I, Raposo, Graça, Rayyan, Morsi S, Regev-Rudzki, Neta, Ricklefs, Franz L, Robbins, Paul D, Roberts, David D, Rodrigues, Silvia C, Rohde, Eva, Rome, Sophie, Rouschop, Kasper Ma, Rughetti, Aurelia, Russell, Ashley E, Saá, Paula, Sahoo, Susmita, Salas-Huenuleo, Edison, Sánchez, Catherine, Saugstad, Julie A, Saul, Meike J, Schiffelers, Raymond M, Schneider, Raphael, Schøyen, Tine Hiorth, Scott, Aaron, Shahaj, Eriomina, Sharma, Shivani, Shatnyeva, Olga, Shekari, Faezeh, Shelke, Ganesh Vilas, Shetty, Ashok K, Shiba, Kiyotaka, Siljander, Pia R-M, Silva, Andreia M, Skowronek, Agata, Snyder, Orman L, Soares, Rodrigo Pedro, Sódar, Barbara W, Soekmadji, Carolina, Sotillo, Javier, Stahl, Philip D, Stoorvogel, Willem, Stott, Shannon L, Strasser, Erwin F, Swift, Simon, Tahara, Hidetoshi, Tewari, Muneesh, Timms, Kate, Tiwari, Swasti, Tixeira, Rochelle, Tkach, Mercedes, Toh, Wei Seong, Tomasini, Richard, Torrecilhas, Ana Claudia, Tosar, Juan Pablo, Toxavidis, Vasilis, Urbanelli, Lorena, Vader, Pieter, van Balkom, Bas Wm, van der Grein, Susanne G, Van Deun, Jan, van Herwijnen, Martijn Jc, Van Keuren-Jensen, Kendall, van Niel, Guillaume, van Royen, Martin E, van Wijnen, Andre J, Vasconcelos, M Helena, Vechetti, Ivan J, Veit, Tiago D, Vella, Laura J, Velot, Émilie, Verweij, Frederik J, Vestad, Beate, Viñas, Jose L, Visnovitz, Tamás, Vukman, Krisztina V, Wahlgren, Jessica, Watson, Dionysios C, Wauben, Marca Hm, Weaver, Alissa, Webber, Jason P, Weber, Viktoria, Wehman, Ann M, Weiss, Daniel J, Welsh, Joshua A, Wendt, Sebastian, Wheelock, Asa M, Wiener, Zoltán, Witte, Leonie, Wolfram, Joy, Xagorari, Angeliki, Xander, Patricia, Xu, Jing, Yan, Xiaomei, Yáñez-Mó, María, Yin, Hang, Yuana, Yuana, Zappulli, Valentina, Zarubova, Jana, Žėkas, Vytautas, Zhang, Jian-Ye, Zhao, Zezhou, Zheng, Lei, Zheutlin, Alexander R, Zickler, Antje M, Zimmermann, Pascale, Zivkovic, Angela M, Zocco, Davide, and Zuba-Surma, Ewa K

Published
2018

28. Allergic Asthmatics Show Divergent Lipid Mediator Profiles from Healthy Controls Both at Baseline and following Birch Pollen Provocation

Author

Lundstrom, Susanna L., Yang, Jun, Kallberg, Henrik J., Thunberg, Sarah, Gafvelin, Guro, Haeggstrom, Jesper Z., Gronneberg, Reidar, Grunewald, Johan, van Hage, Marianne, Hammock, Bruce D., Eklund, Anders, Wheelock, Asa M., Wheelock, Craig E., Lundstrom, Susanna L., Yang, Jun, Kallberg, Henrik J., Thunberg, Sarah, Gafvelin, Guro, Haeggstrom, Jesper Z., Gronneberg, Reidar, Grunewald, Johan, van Hage, Marianne, Hammock, Bruce D., Eklund, Anders, Wheelock, Asa M., and Wheelock, Craig E.

Abstract

Background: Asthma is a respiratory tract disorder characterized by airway hyper-reactivity and chronic inflammation. Allergic asthma is associated with the production of allergen-specific IgE and expansion of allergen-specific T-cell populations. Progression of allergic inflammation is driven by T-helper type 2 (Th2) mediators and is associated with alterations in the levels of lipid mediators. Objectives: Responses of the respiratory system to birch allergen provocation in allergic asthmatics were investigated. Eicosanoids and other oxylipins were quantified in the bronchoalveolar lumen to provide a measure of shifts in lipid mediators associated with allergen challenge in allergic asthmatics. Methods: Eighty-seven lipid mediators representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened via LC-MS/MS following off-line extraction of bronchoalveolar lavage fluid (BALF). Multivariate statistics using OPLS were employed to interrogate acquired oxylipin data in combination with immunological markers. Results: Thirty-two oxylipins were quantified, with baseline asthmatics possessing a different oxylipin profile relative to healthy individuals that became more distinct following allergen provocation. The most prominent differences included 15-LOX-derived omega-3 and omega-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R-2 = 0.7) between OPLS models for baseline asthmatics ((RY)-Y-2[cum] = 0.87, Q(2)[cum] = 0.51) and allergen-provoked asthmatics ((RY)-Y-2[cum] = 0.95, Q(2)[cum] = 0.73), with the majority of quantified lipid mediators and cytokines contributing equally to both groups. Unique structures for allergen provocation included leukotrienes (LTB4 and 6-trans-LTB4), CYP-derivatives of linoleic acid (epoxides/diols), and IL-10. Conclusions: Differences in asthmatic relative to healthy profiles suggest a role for 15-LOX products of both omega-6 and omega-3 origin in allerg, QC 20170419

Published
2012
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29. Building Multivariate Systems Biology Models

Author

Kirwan, Gemma M, Johansson, Erik, Kleemann, Robert, Verheij, Elwin R, Wheelock, Asa M, Goto, Susumu, Trygg, Johan, Wheelock, Craig E, Kirwan, Gemma M, Johansson, Erik, Kleemann, Robert, Verheij, Elwin R, Wheelock, Asa M, Goto, Susumu, Trygg, Johan, and Wheelock, Craig E

Abstract

Systems biology methods using large-scale "omics" data sets face unique challenges: integrating and analyzing near limitless data space, while recognizing and removing systematic variation or noise. Herein we propose a complementary multivariate analysis workflow to both integrate "omics" data from disparate sources and analyze the results for specific and unique sample correlations. This workflow combines principal component analysis (PCA), orthogonal projections to latent structures discriminate analysis (OPLS-DA), orthogonal 2 projections to latent structures (O2PLS), and shared and unique structures (SUS) plots. The workflow is demonstrated using data from a study in which ApoE3Leiden mice were fed an atherogenic diet consisting of increasing cholesterol levels followed by therapeutic intervention (fenofibrate, rosuvastatin, and LXR activator T-0901317). The levels of structural lipids (lipidomics) and free fatty acids in liver were quantified via liquid chromatography-mass spectrometry (LC-MS). The complementary workflow identified diglycerides as key hepatic metabolites affected by dietary cholesterol and drug intervention. Modeling of the three therapeutics for mice fed a high-cholesterol diet further highlighted diglycerides as metabolites of interest in atherogenesis, suggesting a role in eliciting chronic liver inflammation. In particular, O2PLS-based SUS2 plots showed that treatment with T-0901317 or rosuvastatin returned the diglyceride profile in high-cholesterol-fed mice to that of control animals.

Published
2012
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34. Difference In Oxylipin Levels And Exosome Content In Bronchoalveolar Lavage Fluid Of Asthmatics And Healthy Individuals In Response To Subway Air Exposure

Author

Levänen, Bettina, primary, Lundström, Susanna L., additional, Torregrosa Paredes, Patricia, additional, Nording, Malin L., additional, Klepczynska Nyström, Anna, additional, Sköld, Magnus C., additional, Haeggström, Jesper Z., additional, Grunewald, Johan, additional, Svartengren, Magnus, additional, Hammock, Bruce D., additional, Gabrielsson, Susanne, additional, Larsson, Britt-Marie, additional, Eklund, Anders, additional, Wheelock, Craig E., additional, Erle, David J., additional, and Wheelock, Asa M., additional

Published
2010
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35. Lung density on high resolution computer tomography (HRCT) reflects degree of inflammation in smokers.

Author

Karimi, Reza, Tornling, Göran, Forsslund, Helena, Mikko, Mikael, Wheelock, Asa M, Nyrén, Sven, Sköld, Carl Magnus, and Wheelock, Åsa M

Subjects
OBSTRUCTIVE lung disease diagnosis, LUNG radiography, COMPUTED tomography, HUMAN reproduction, INFLAMMATION, OBSTRUCTIVE lung diseases, SMOKING, VITAL capacity (Respiration), DIAGNOSIS
Abstract

Background: Smokers have increased cell concentration in the lower respiratory tract indicating a chronic inflammatory state, which in some individuals may lead to development of chronic obstructive pulmonary disease (COPD). Computer tomography (CT) imaging provides means of quantifying pulmonary structure and early signs of disease. We investigated whether lung density on high resolution CT differs between smokers and never-smokers and if this were associated to intensity of inflammation.Methods: Forty smoking volunteers with normal pulmonary function, 40 healthy never-smokers and 40 patients with COPD of GOLD stage I-II, were included. Mean lung attenuation and percentage of pixels in the lung with attenuation between -750 and -900 HU (percentage higher density spectrum (%HDS)) were calculated on inspiratory CT-scans. Markers of systemic inflammation in blood and cell counts in bronchoalveolar lavage (BAL) fluid were recorded.Results: Lung density expressed as %HDS was increased in smokers (44.0 ± 5.8%) compared to both never-smokers (38.3 ± 5.8%) and patients with COPD (39.1 ± 5.8%), (p < 0.001, for both). Females had denser lungs than males, which was dependent on body height. Cell concentration in BAL were correlated to lung density in smokers (r = 0.50, p < 0.001).Conclusions: Lung density on CT is associated with cell concentration in BAL in smokers and may mirror an inflammatory response in the lung. Gender difference in lung density is dependent on height. In COPD with emphysema, loss of lung tissue may counterbalance the expected increase in density due to inflammation. The findings may help to interpret high resolution CT in the context of smoking and gender and highlight the heterogeneity of structural changes in COPD. [ABSTRACT FROM AUTHOR]

Published
2014
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36. Radiomultiomics: quantitative CT clusters of severe asthma associated with multiomics.

Author

Zounemat Kermani N, Chung KF, Macis G, Santini G, Clemeno FAA, Versi A, Sun K, Abdel-Aziz MI, Andersson LI, Auffray C, Badi Y, Bakke P, Brightling C, Brinkman P, Caruso M, Chanez P, De Meulder B, Djukanovic R, Fabbri L, Fowler SJ, Horvath I, Howarth P, James AJ, Kolmert J, Kraft M, Li CX, Maitland-van der Zee AH, Malerba M, Papi A, Rabe K, Sanak M, Shaw DE, Singh D, Sparreman Mikus M, van Den Berge M, Wheelock AM, Wheelock CE, Yasinska V, Guo YK, Wagers S, Barnes PJ, Bush A, Sterk PJ, Dahlen SE, Adcock IM, Siddiqui S, and Montuschi P

Subjects
Humans, Female, Male, Middle Aged, Adult, Proteomics, rac1 GTP-Binding Protein metabolism, Sputum metabolism, Cohort Studies, Cluster Analysis, Severity of Illness Index, Machine Learning, Aged, Multiomics, Asthma diagnostic imaging, Asthma metabolism, Tomography, X-Ray Computed, Lung diagnostic imaging
Abstract

Background: Lung quantitative computed tomography (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways, using radiomultiomics, integrating qCT, multiomics and machine learning/artificial intelligence., Methods: We used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort. The same qCT measurements were used to replicate qCT clusters in a subsample of the ATLANTIS asthma cohort (n=97). We performed integrated enrichment analysis using blood, sputum, bronchial biopsies, bronchial brushings and nasal brushings transcriptomics and blood and sputum proteomics to characterise radiomultiomic-associated clusters (RACs)., Results: qCT clusters and clinical features in U-BIOPRED were replicated in the matched ATLANTIS cohort. In the U-BIOPRED cohort, RAC1 (n=30) was predominantly female with elevated body mass index, mild airflow limitation, decreased CT lung volume and increased lung density and upregulation of the complement pathway. RAC2 (n=34) subjects had airway wall thickness and a mild degree of airflow limitation, with upregulation of proliferative pathways including neurotrophic receptor tyrosine kinase 2/tyrosine kinase receptor B, and downregulation of semaphorin pathways. RAC3 (n=41) showed increased lung attenuation area and air trapping, severe airflow limitation, hyperinflation, and upregulation of cytokine signalling and signalling by interleukin pathways, and matrix metallopeptidase 1, 2 and 9., Conclusions: U-BIOPRED severe asthma qCT clusters were replicated in a matched independent asthmatic cohort and associated with specific molecular pathways. Radiomultiomics might represent a novel strategy to identify new molecular pathways in asthma pathobiology., Competing Interests: Conflict of interest: K.F. Chung reports grants from the MRC, EPSRC, GSK, Merck and NIEHS, payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK, Novartis and AstraZeneca, and participation on a data safety monitoring board or advisory board with GSK, AstraZeneca, Novartis, Roche, Merck, Trevi, Rickett-Beckinson, Nocion, Shionogi and Clean Breathing Institute supported by Haleon. C. Auffray reports support for the present study from the Innovative Medicines Initiative. Y. Badi reports support for the present study from the Innovative Medicines Initiative. P. Bakke reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GSK and Sanofi. C. Brightling reports support for the present study from the ATLANTIS study (Chiesi grant) and Leicester NIHR BRC, grants from 4D Pharma, Areteia, AstraZeneca, Chiesi, Genentech, GSK, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi, and consultancy fees from 4D Pharma, Areteia, AstraZeneca, Chiesi, Genentech, GSK, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi. P. Chanez reports grants from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis and Sanofi Aventis, consultancy fees from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis and Sanofi Aventis, payment or honoraria for lectures, presentations, manuscript writing or educational events from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis and Sanofi Aventis, and support for attending meetings from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis and Sanofi Aventis. B. De Meulder reports support for the present study from the Innovative Medicines Initiative. R. Djukanovic reports consultancy fees from Synairgen plc, GSK, ZenasBio and Celltrion, leadership role as Chair of the European Respiratory Society's clinical research collaboration on severe asthma (SHARP), and stock (or stock options) with Synairgen plc. L. Fabbri reports consultancy fees from Chiesi Farmaceutici and AstraZeneca, payment or honoraria for lectures, presentations, manuscript writing or educational events from Chiesi Farmaceutici, AstraZeneca, GSK, Alfasigma and Novartis, support for attending meetings from Chiesi Farmaceutici, GSK and Novartis, and participation on a data safety monitoring board or advisory board with Novartis and Chiesi. S.J. Fowler reports grants from the NIHR, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Boehringer Ingelheim. P. Howarth reports employment with GSK. J. Kolmert reports consultancy fees from Gesynta Pharma AB and Lipum AB. M. Kraft reports grants from the NIH, American Lung Association, Synairgen, Janssen, AstraZeneca and Sanofi, consultancy fees from AstraZeneca, Sanofi, Chiesi, GSK, Kinaset and Genentech, payment or honoraria for lectures, presentations, manuscript writing or educational events from Chiesi, support for attending meetings from the European Respiratory Society, one patent issued and tiled filed to development of therapeutics for inflammatory lung disease as CoFounder and Chief Medical Officer, RaeSedo, Inc., participation on a data safety monitoring board or advisory board with ALung, leadership role with the National Heart, Lung and Blood Advisory Council, stock (or stock options) with RaeSedo, Inc. (equity ownership), and the following financial (or non-financial) interests: Section Editor of UpToDate. A.H. Maitland-van der Zee reports grants from Health Holland, GSK, Boehringer Ingelheim and Vertex, consultancy fees from Boehringer Ingelheim and AstraZeneca, payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK, and participation on a data safety monitoring board or advisory board for a study on BPD in neonates. A. Papi reports grants from Chiesi, AstraZeneca, GSK and Sanofi, consultancy fees from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, Moderna and Roche, payment or honoraria for lectures, presentations, manuscript writing or educational events from Chiesi, AstraZeneca, GSK, Menarini, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion, Sanofi and Regeneron, participation on a data safety monitoring board or advisory board with Chiesi, AstraZeneca, GSK, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals and Moderna, receipt of equipment, materials, drugs, medical writing, gifts or other services from Consorzio Futuro in Ricerca. K. Rabe reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, Novartis, Sanofi/Regeneron, GSK, Berlin Chemie and Roche Pharma, participation on a data safety monitoring board or advisory board with AstraZeneca, Boehringer Ingelheim, Sanofi/Regeneron and CSL Behring, and leadership roles with the German Center for Lung Research (DZL), German Chest Society (DGP) and American Thoracic Society. D.E. Shaw reports consultancy fees from GSK, AstraZeneca and Novartis, payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK and AstraZeneca, and support for attending meetings from GSK. D. Singh reports consultancy fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, EpiEndo, Genentech, GSK, Glenmark, Gossamer Bio, Kinaset Therapeutics, Menarini, Novartis, Orion, Pulmatrix, Sanofi, Synairgen, Teva, Theravance, Biopharma and Verona Pharma. M. van Den Berge reports grants from GSK, Roche, Genentech and Novartis. Y. Guo reports support for the present study from the Innovative Medicines Initiative. S. Wagers reports consultancy fees from King's College Hospital NHS Foundation Trust, Academic Medical Research, AMC Medical Research BV, Asthma UK, Athens Medical School, Boehringer Ingelheim International GmbH, CHU de Toulouse, CIRO, DS Biologicals Ltd, École Polytechnique Fédérale De Lausanne, European Respiratory Society, FISEVI, Fluidic Analytics Ltd, Fraunhofer IGB, Fraunhofer ITEM, GSK Research & Development Ltd, Holland & Knight, Karolinska Institutet Fakturor, KU Leuven, Longfonds, National Heart and Lung Institute, Novartis Pharma AG, Owlstone Medical Limited, PExA AB, UCB Biopharma SPRL, Umeå University, University Hospital Southampton NHS Foundation Trust, Università Campus Bio-Medico di Roma, Universita Cattolica Del Sacro Cuore, Universität Ulm, University of Bern, University of Edinburgh, University of Hull, University of Leicester, University of Loughborough, University of Luxembourg, University of Manchester, University of Nottingham, Vlaams Brabant, Dienst Europa, Imperial College London, Boehringer Ingelheim, Breathomix, Gossamer Bio, AstraZeneca, CIBER, OncoRadiomics, University of Leiden, University of Wurzburg, Chiesi Pharmaceutical, University of Liege, Teva Pharmaceuticals, Sanofi, Pulmonary Fibrosis Foundation and Three Lakes Foundation. P.J. Sterk reports consultancy fees from SME Breathomix, and stock (or stock options) with SME Breathomix. S-E. Dahlen reports grants from AstraZeneca, GSK and Sanofi, consultancy fees from AstraZeneca, Cayman Chemicals, GSK and Regeneron, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GSK and Sanofi. I.M. Adcock reports support for the present study from the Innovative Medicines Initiative, grants from GSK, MRC, EPSRC and Sanofi, consultancy fees from GSK, Sanofi, Chiesi and Kinaset, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Sanofi, Eurodrug and Sunovion, and support for attending meetings from AstraZeneca. S. Siddiqui consultancy fees from AstraZeneca, GSK, CSL Behring, Areteia Therapeutics, ERT Medical, Chiesi and Roche, and payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK, Chiesi and AstraZeneca. P. Montuschi reports support for the present study from the Innovative Medicines Initiative. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Published
2024
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37. The chitinase-like protein YKL-40: a possible biomarker of inflammation and airway remodeling in severe pediatric asthma.

Author

Konradsen JR, James A, Nordlund B, Reinius LE, Söderhäll C, Melén E, Wheelock AM, Lödrup Carlsen KC, Lidegran M, Verhoek M, Boot RG, Dahlén B, Dahlén SE, and Hedlin G

Subjects
Adipokines genetics, Adolescent, Asthma physiopathology, Case-Control Studies, Child, Chitinase-3-Like Protein 1, Cross-Sectional Studies, Exhalation, Female, Humans, Lectins genetics, Lung chemistry, Lung metabolism, Male, Nitric Oxide analysis, Severity of Illness Index, Surveys and Questionnaires, Adipokines blood, Airway Remodeling physiology, Asthma blood, Biomarkers blood, Growth Substances blood, Inflammation metabolism, Lectins blood
Abstract

Background: Problematic severe childhood asthma includes a subgroup of patients who are resistant to therapy. The specific mechanisms involved are unknown, and novel biomarkers are required to facilitate treatment and diagnosis of therapy-resistant asthma. The chitinase-like protein YKL-40 has been related to asthma and airway remodeling., Objectives: To compare serum YKL-40 levels in children with severe, therapy-resistant asthma (n = 34), children with controlled persistent asthma (n = 39), and healthy controls (n = 27), and to investigate correlations with biomarkers of inflammation and airway remodeling., Methods: The study protocol included questionnaires, measurement of exhaled nitric oxide in exhaled air, blood sampling for inflammatory biomarkers, and high-resolution computed tomography of the lungs to identify bronchial wall thickening (therapy-resistant only). Serum YKL-40 levels were measured by ELISA, and all asthmatic children were genotyped for a CHI3L1 promoter single nucleotide polymorphism (rs4950928)., Results: Serum YKL-40 levels were significantly higher in children with therapy-resistant asthma than in healthy children (19.2 ng/mL vs 13.8 ng/mL, P = .03). Among children with severe, therapy-resistant asthma, YKL-40 levels correlated with fraction of exhaled nitric oxide in exhaled air (r = 0.48, P = .004), blood neutrophils (r = 0.63, P < .001), and bronchial wall thickening on high-resolution computed tomography (r = 0.45, P = .01). Following adjustment for CHI3L1 genotype, significantly greater levels of YKL-40 were found in children with therapy-resistant asthma than in children with controlled asthma., Conclusions: YKL-40 levels are increased in children with severe, therapy-resistant asthma compared to healthy children, and also compared to children with controlled asthma following correction for genotype., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Published
2013
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38. In the eye of the beholder: does the master see the SameSpots as the novice?

Author

Silva E, O'Gorman M, Becker S, Auer G, Eklund A, Grunewald J, and Wheelock AM

Subjects
Analysis of Variance, Reproducibility of Results, Software, Subtraction Technique, Algorithms, Electrophoresis, Gel, Two-Dimensional methods, Image Processing, Computer-Assisted methods
Abstract

Historically, the use of two-dimensional electrophoresis (2-DE) in quantitative proteomics has been hampered by significant technical variance. Over the past decade, a range of technological leaps have reduced the overall variance of 2-DE, thus turning the technology into a robust platform for quantitative intact proteomics. However, as the confounding gel-to-gel variation improves, the variance arising from the subsequent image analysis becomes more prominent. Limitations in image alignment and spot detection of previous generations of 2-DE analysis software have demanded considerable user-intervention and manual editing, resulting in introduction of a large degree of subjectivity and software-induced variance. We evaluated the performance of SameSpots, representing a new generation of 2-DE image analysis software, using both DIGE and traditional single-stain 2-DE approaches. Evaluations of the software-induced variance in relation to other sources of variance, as well as the subjectivity through comparison of analyses performed by an expert user and a novice lab-user, were performed. In terms of statistical power, the less-experienced user achieved the better results, but no discernible difference was detected in multivariate comparisons between the users. In conclusion, we found that SameSpots represents improvements both in reproducibility and objectivity in relation to previous generations of 2-DE analysis software.

Published
2010
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39. The use of network analyses for elucidating mechanisms in cardiovascular disease.

Author

Diez D, Wheelock AM, Goto S, Haeggström JZ, Paulsson-Berne G, Hansson GK, Hedin U, Gabrielsen A, and Wheelock CE

Subjects
Female, Gene Expression Profiling methods, Genomics methods, Humans, Male, Models, Biological, Atherosclerosis genetics, Atherosclerosis metabolism, Systems Biology methods
Abstract

Systems biology offers the potential to provide new insights into our understanding of the pathogenesis of complex diseases such as atherosclerosis. It seeks to comprehend the system properties of the non-linear interactions of the multiple biomolecular components that characterize a living organism. An important component of this research approach is identifying the biological networks that connect the differing elements of a system and in the process describe the characteristics that define a shift in equilibrium from a healthy to a diseased state. The utility of this method becomes clear when applied to multifactorial diseases with complex etiologies such as inflammatory-related diseases, herein exemplified by cardiovascular disease. In this study, the application of network theory to systems biology is described in detail and an example is provided using data from a clinical biobank database of carotid endarterectomies from the Karolinska University Hospital (Biobank of Karolinska Endarterectomies, BiKE). Data from 47 microarrays were examined using a combination of Bioconductor modules and the Cytoscape resource with several associated plugins to analyze the transcriptomics data and create a combined gene association and correlation network of atherosclerosis. The methodology and workflow are described in detail, with a total of 43 genes found to be differentially expressed on a gender-specific basis, of which 15 were not directly linked to the sex chromosomes. In particular, the APOC1 gene was 2.1-fold down-regulated in plaques in women relative to men and was selected for further analysis based upon a purported role in cardiovascular disease. The resulting network was identified as a scale-free network that contained specific sub-networks related to immune function and lipid biosynthesis. These sub-networks link atherosclerotic-related genes to other genes that may not have previously known roles in disease etiology and only evidence small alterations, which are challenging to find by statistical and comparison-based methods. A number of Gene Ontology (GO), BioCarta and KEGG pathways involved in the atherosclerotic process were identified in the constructed sub-network, with 19 GO pathways related to APOC1 of which 'phospholipid efflux' evidenced the strongest association. The utility and functionality of network analysis and the different Cytoscape plugins employed are discussed. Lastly, the applications of these methods to cardiovascular disease are discussed with focus on the current limitations and future visions of this emerging field.

Published
2010
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40. Systems biology approaches and pathway tools for investigating cardiovascular disease.

Author

Wheelock CE, Wheelock AM, Kawashima S, Diez D, Kanehisa M, van Erk M, Kleemann R, Haeggström JZ, and Goto S

Subjects
Animals, Cardiovascular Diseases genetics, Gene Expression Profiling, Humans, Lipid Metabolism, Models, Biological, Systems Biology trends, Cardiovascular Diseases metabolism, Metabolic Networks and Pathways, Software, Systems Biology methods
Abstract

Systems biology aims to understand the nonlinear interactions of multiple biomolecular components that characterize a living organism. One important aspect of systems biology approaches is to identify the biological pathways or networks that connect the differing elements of a system, and examine how they evolve with temporal and environmental changes. The utility of this method becomes clear when applied to multifactorial diseases with complex etiologies, such as inflammatory-related diseases, herein exemplified by atherosclerosis. In this paper, the initial studies in this discipline are reviewed and examined within the context of the development of the field. In addition, several different software tools are briefly described and a novel application for the KEGG database suite called KegArray is presented. This tool is designed for mapping the results of high-throughput omics studies, including transcriptomics, proteomics and metabolomics data, onto interactive KEGG metabolic pathways. The utility of KegArray is demonstrated using a combined transcriptomics and lipidomics dataset from a published study designed to examine the potential of cholesterol in the diet to influence the inflammatory component in the development of atherosclerosis. These data were mapped onto the KEGG PATHWAY database, with a low cholesterol diet affecting 60 distinct biochemical pathways and a high cholesterol exposure affecting 76 biochemical pathways. A total of 77 pathways were differentially affected between low and high cholesterol diets. The KEGG pathways "Biosynthesis of unsaturated fatty acids" and "Sphingolipid metabolism" evidenced multiple changes in gene/lipid levels between low and high cholesterol treatment, and are discussed in detail. Taken together, this paper provides a brief introduction to systems biology and the applications of pathway mapping to the study of cardiovascular disease, as well as a summary of available tools. Current limitations and future visions of this emerging field are discussed, with the conclusion that combining knowledge from biological pathways and high-throughput omics data will move clinical medicine one step further to individualize medical diagnosis and treatment.

Published
2009
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41. Troubleshooting image analysis in 2DE.

Author

Levänen B and Wheelock AM

Subjects
Algorithms, Proteins analysis, Proteomics methods, Software, Electrophoresis, Gel, Two-Dimensional methods, Image Processing, Computer-Assisted instrumentation, Image Processing, Computer-Assisted methods
Abstract

The image analysis part of gel-based proteome research plays an important role in the overall success of the experiment. The main purpose of software-assisted 2DE gel analysis is to detect the protein spots, match them between gels within an experiment, and identify any differences in protein expression between sets of samples. Efficient analysis of protein expression relies on automated image processing techniques. There are several factors to consider in the choice of software product, as well as in the implementation of the analysis itself. Successful quantification of protein expression levels is largely dependent on the algorithms for spot matching, normalization, and background subtraction provided by the 2DE analysis software. In addition to generic protocols for image acquisition and subsequent 2DE image analysis (using Progenesis PG200), this chapter describes methods for quantitative and qualitative evaluation of the quality of the image analysis.

Published
2009
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42. HPLC/MS/MS-based approaches for detection and quantification of eicosanoids.

Author

Lundström SL, D'Alexandri FL, Nithipatikom K, Haeggström JZ, Wheelock AM, and Wheelock CE

Subjects
Bronchoalveolar Lavage Fluid, Cyclotrons, Fourier Analysis, Chromatography, High Pressure Liquid methods, Eicosanoids analysis, Tandem Mass Spectrometry methods
Abstract

Eicosanoids are oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. Detection and quantification of these compounds are of great interest because they play important roles in a number of significant diseases, including asthma, chronic obstructive pulmonary disease (COPD), cardiovascular disease, and cancer. Because the endogenous levels of eicosanoids are quite low, sensitive and specific analytical methods are required to reliably quantify these compounds. High-performance liquid chromatography mass spectrometry (HPLC/MS) has emerged as one of the main techniques used in eicosanoid profiling. Herein, we describe the main LC/MS techniques and principles as well as their application in eicosanoid analysis. In addition, a protocol is given for extracting eicosanoids from biological samples, using bronchoalveolar lavage fluid (BALF) as an example. The method and instrument optimization procedures are presented, followed by the analysis of eicosanoid standards using reverse phase HPLC interfaced with an ion trap mass spectrometer (LC/MS/MS). This protocol is intended to provide a broad description of the field for readers looking for an introduction to the methodologies involved in eicosanoid quantification.

Published
2009
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43. From Genome to Proteome: Integration and proteome completion - 8th Siena Meeting.

Author

Wheelock AM and Wheelock CE

Subjects
Biological Evolution, Biomarkers blood, Humans, Proteome, Genome, Human, Proteomics trends
Abstract

The Siena Meeting is designed to cover the breadth of proteomics-based research, with a particular focus on clinical applications as well as emerging technologies. As in previous years, the 2008 meeting attracted a mix of academic, clinical and industrial scientists, providing a unique opportunity for interactions among these researchers and an excellent environment for research discussions and the formation of new collaborations. The coverage of topics ranged from a bioinformatics recreation of the human proteome to the simultaneous quantification of changes in an entire proteome. Specifically, several technological advances in proteomics, with particular focus on proteome quantification methodologies, were addressed. Current bottlenecks in the field were also examined, including biomarker verification strategies and the development of bioinformatics resources.

Published
2008

44. A framework for determining outlying microarray experiments.

Author

Wan R, Wheelock AM, and Mamitsuka H

Subjects
Computer Graphics, Computer Simulation, DNA, Complementary genetics, Gene Expression Regulation, Probability, Statistics as Topic, Models, Genetic, Oligonucleotide Array Sequence Analysis
Abstract

Microarrays are high-throughput technologies whose data are known to be noisy. In this work, we propose a graph-based method which first identifies the extent to which a single microarray experiment is noisy and then applies an error function to clean individual expression levels. These two steps are unified within a framework based on a graph representation of a separate data set from some repository. We demonstrate the utility of our method by comparing our results against statistical methods by applying both techniques to simulated microarray data. Our results are encouraging and indicate one potential use of microarray data from past experiments.

Published
2008

45. Use of a fluorescent internal protein standard to achieve quantitative two-dimensional gel electrophoresis.

Author

Wheelock AM, Morin D, Bartosiewicz M, and Buckpitt AR

Subjects
Animals, Chromogenic Compounds chemistry, Electrophoresis, Gel, Two-Dimensional instrumentation, Fluorescent Dyes chemical synthesis, Luminescent Measurements, Male, Phenanthrolines chemistry, Proteomics methods, Random Allocation, Rats, Rats, Sprague-Dawley, Reference Standards, Ruthenium Compounds chemistry, Electrophoresis, Gel, Two-Dimensional methods, Electrophoresis, Gel, Two-Dimensional standards, Fluorescent Dyes chemistry, Proteins chemistry
Abstract

2-DE is a powerful separation method for complex protein mixtures. However, large intergel variations in spot intensity limit its use for quantitative proteomics studies. To address this issue, we developed a fluorescent internal protein standard for use in 2-DE analysis. Protein samples are spiked with an Alexa-labeled internal standard (ALIS) prior to separation with 2-DE. Due to the high extinction coefficient of the Alexa-fluor, incorporation of 0.1% of total protein is sufficient to allow visualization of the internal standard yet low enough to avoid interference in subsequent quantification and identification steps. Following 2-DE, total proteins are visualized with fluorescent postelectrophoretic stains spectrally separated from ALIS. Four protein stains, Deep Purple, Sulforhodamine G, ruthenium II-tris(bathophenanthroline disulfonate) (RuTBS), and SYPRO Ruby, including improved purification and staining protocols for RuTBS and ten-fold dilutions of SYPRO Ruby were evaluated. All staining protocols were compatible with the ALIS method and had similar LODs (1-4 ng) and dynamic ranges (10(3)). ALIS is a powerful normalization method for quantitative 2-DE which avoids potential problems associated with dual spot migration patterns observed in the DIGE method. Furthermore, ALIS provides significantly improved normality in the distribution of spot abundance-variance compared to normalization through division by the total spot volume.

Published
2006
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46. Effects of post-electrophoretic analysis on variance in gel-based proteomics.

Author

Wheelock AM and Goto S

Subjects
Electrophoresis, Gel, Two-Dimensional economics, Proteomics methods
Abstract

2D electrophoresis (2DE) is a prominent separation method for complex proteomes. Although recent advances have increased the utility of this method in quantitative proteomics studies, many sources of variance still exist. This review discusses the post-electrophoretic sources of variance in current 2DE analysis. The essential improvements in protein visualization and software algorithms that have made 2DE a leading quantitative proteomics method are briefly reviewed. A number of shortcomings in the post-electrophoretic analysis of 2DE data that require further attention are highlighted. Topics discussed include protein visualization and image acquisition, internal standards and normalization methods, background subtraction algorithms, normality of distribution, and the need for standardized tests for the evaluation of 2DE analysis software packages.

Published
2006
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47. Software-induced variance in two-dimensional gel electrophoresis image analysis.

Author

Wheelock AM and Buckpitt AR

Subjects
Algorithms, Animals, Male, Rats, Rats, Sprague-Dawley, Reproducibility of Results, Respiratory Mucosa metabolism, Electrophoresis, Gel, Two-Dimensional, Image Processing, Computer-Assisted, Proteome metabolism, Software Validation
Abstract

Experimental variability in 2-DE is well documented, but little attention has been paid to variability arising from postexperimental quantitative analyses using various 2-DE software packages. The performance of two 2-DE analysis software programs, Phoretix 2D Expression v2004 (Expression) and PDQuest 7.2 (PDQuest), was evaluated in this study. All available background subtraction and smoothing algorithms were tested using both data generated from one single 2-DE gel image, thus excluding experimental variance, and with authentic sets of replicate gels (n = 5). A slight shift of the image boundaries (the "cropping area") caused both programs to induce variance in protein spot quantification of otherwise identical gel images. The resulting variance for PDQuest (CV(mean) = 8%) was approximately twice that for Expression (CV(mean) = 4%). In authentic sets of replicate 2-DE gels (n = 5), the experimental variance confounded the software-induced variance to some extent. However, Expression still outperformed PDQuest, which exhibited software-induced variance as high as 25% of the total observed variance. Surprisingly, the complete omission of background subtraction algorithms resulted in the least amount of software-based variance. These data indicate that 2-DE gel analysis software constitutes a significant source of the variance observed in quantitative proteomics, and that the use of background subtraction algorithms can further increase the variance.

Published
2005
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