184 results on '"Herman, Stephanie"'
Search Results
2. Profound but Transient Changes in the Inflammatory Milieu of the Blood During Autologous Hematopoietic Stem Cell Transplantation
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Wiberg, Anna, Olsson-Strömberg, Ulla, Herman, Stephanie, Kultima, Kim, and Burman, Joachim
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- 2020
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3. Metabolic drift in the aging nervous system is reflected in human cerebrospinal fluid
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Peters, Kristian, Herman, Stephanie, Khoonsari, Payam Emami, Burman, Joachim, Neumann, Steffen, and Kultima, Kim
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- 2021
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4. Systematic analysis of the cerebrospinal fluid proteome of fibromyalgia patients
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Khoonsari, Payam Emami, Musunri, Sravani, Herman, Stephanie, Svensson, Camilla I., Tanum, Lars, Gordh, Torsten, and Kultima, Kim
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- 2019
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5. Autologous hematopoietic stem cell transplantation significantly alters circulating ceramides in peripheral blood of relapsing-remitting multiple sclerosis patients
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Vaivade, Aina, primary, Wiberg, Anna, additional, Khoonsari, Payam Emami, additional, Carlsson, Henrik, additional, Herman, Stephanie, additional, Al-Grety, Asma, additional, Freyhult, Eva, additional, Olsson-Strömberg, Ulla, additional, Burman, Joachim, additional, and Kultima, Kim, additional
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- 2023
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6. Targeted metabolomics of CSF in healthy individuals and patients with secondary progressive multiple sclerosis using high-resolution mass spectrometry
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Carlsson, Henrik, Abujrais, Sandy, Herman, Stephanie, Khoonsari, Payam Emami, Åkerfeldt, Torbjörn, Svenningsson, Anders, Burman, Joachim, and Kultima, Kim
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- 2020
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7. Autologous hematopoietic stem cell transplantation significantly alters circulating ceramides in peripheral blood of relapsing-remitting multiple sclerosis patients
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Vaivade, Aina, Wiberg, Anna, Emami Khoonsari, Payam, Carlsson, Henrik, Herman, Stephanie, Al-Grety, Asma, Freyhult, Eva, Olsson-Stromberg, Ulla, Burman, Joachim, Kultima, Kim, Vaivade, Aina, Wiberg, Anna, Emami Khoonsari, Payam, Carlsson, Henrik, Herman, Stephanie, Al-Grety, Asma, Freyhult, Eva, Olsson-Stromberg, Ulla, Burman, Joachim, and Kultima, Kim
- Abstract
Background: The common inflammatory disease multiple sclerosis (MS) is a disease of the central nervous system. For more than 25 years autologous hematopoietic stem cell transplantation (AHSCT) has been used to treat MS. It has been shown to be highly effective in suppressing inflammatory activity in relapsing-remitting MS (RRMS) patients. This treatment is thought to lead to an immune system reset, inducing a new, more tolerant system; however, the precise mechanism behind the treatment effect in MS patients is unknown. In this study, the effect of AHSCT on the metabolome and lipidome in peripheral blood from RRMS patients was investigated. Methods: Peripheral blood samples were collected from 16 patients with RRMS at ten-time points over the five months course of AHSCT and 16 MS patients not treated with AHSCT. Metabolomics and lipidomics analysis were performed using liquid-chromatography high-resolution mass spectrometry. Mixed linear models, differential expression analysis, and cluster analysis were used to identify differentially expressed features and groups of features that could be of interest. Finally, in-house and in-silico libraries were used for feature identification, and enrichment analysis was performed. Results: Differential expression analysis found 657 features in the lipidomics dataset and 34 in the metabolomics dataset to be differentially expressed throughout AHSCT. The administration of cyclophosphamide during mobilization and conditioning was associated with decreased concentrations in glycerophosphoinositol species. Thymoglobuline administration was associated with an increase in ceramide and glycerophosphoethanolamine species. After the conditioning regimen, a decrease in glycerosphingoidlipids concentration was observed, and following hematopoietic stem cell reinfusion glycerophosphocholine concentrations decreased for a short period of time. Ceramide concentrations were strongly associated with leukocyte levels during the procedure. The
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- 2023
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8. Alterations in the tyrosine and phenylalanine pathways revealed by biochemical profiling in cerebrospinal fluid of Huntington’s disease subjects
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Herman, Stephanie, Niemelä, Valter, Emami Khoonsari, Payam, Sundblom, Jimmy, Burman, Joachim, Landtblom, Anne-Marie, Spjuth, Ola, Nyholm, Dag, and Kultima, Kim
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- 2019
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9. Additional file 1 of Autologous hematopoietic stem cell transplantation significantly alters circulating ceramides in peripheral blood of relapsing-remitting multiple sclerosis patients
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Vaivade, Aina, Wiberg, Anna, Khoonsari, Payam Emami, Carlsson, Henrik, Herman, Stephanie, Al-Grety, Asma, Freyhult, Eva, Olsson-Strömberg, Ulla, Burman, Joachim, and Kultima, Kim
- Abstract
Supplementary Material 1
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- 2023
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10. Mass spectrometry based metabolomics for in vitro systems pharmacology: pitfalls, challenges, and computational solutions
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Herman, Stephanie, Emami Khoonsari, Payam, Aftab, Obaid, Krishnan, Shibu, Strömbom, Emil, Larsson, Rolf, Hammerling, Ulf, Spjuth, Ola, Kultima, Kim, and Gustafsson, Mats
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- 2017
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11. Urokinase, CX3CL1, CCL2, TRAIL and IL-18 induced by interferon-β treatment
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Zhukovsky, Christina, Herman, Stephanie, Wiberg, Anna, Cunningham, Janet, Kultima, Kim, Burman, Joachim, Zhukovsky, Christina, Herman, Stephanie, Wiberg, Anna, Cunningham, Janet, Kultima, Kim, and Burman, Joachim
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Objective To identify serum proteins associated with MS and affected by interferon beta treatment. Methods Plasma samples from 29 untreated relapsing-remitting MS patients and 15 healthy controls were investigated with a multiplexed panel containing 92 proteins related to inflammation. Follow-up samples were available from 13 patients at 1 and 3 months after initiation of treatment with interferon beta-1a. Results Ten proteins were differentially expressed in MS patients. Five of these were altered by treatment with IFN-β 1a: uPA, CX3CL1, CCL2, TRAIL and IL18. Conclusion CCL2 and TRAIL were confirmed to be modulated with interferon beta treatment in MS. As novel findings, we now report that uPA and CX3CL1 were differentially expressed in MS and increased after IFN-beta-1a treatment. Conflicting results have been reported on how interferon beta affects IL-18., Title in Web of Science: Urokinase, CX3CL1, CCL2, TRAIL and IL-18 induced by interferon-beta treatment
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- 2021
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12. Approaches for containerized scientific workflows in cloud environments with applications in life science
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Spjuth, Ola, Capuccini, Marco, Carone, Matteo, Larsson, Anders, Schaal, Wesley, Novella, Jon Ander, Stein, Oliver, Ekmefjord, Morgan, Tommaso, Paolo Di, Floden, Evan, Notredame, Cedric, Moreno, Pablo, Hellander, Andreas, Emami Khoonsari, Payam, Herman, Stephanie, Kultima, Kim, Lampa, Samuel, Spjuth, Ola, Capuccini, Marco, Carone, Matteo, Larsson, Anders, Schaal, Wesley, Novella, Jon Ander, Stein, Oliver, Ekmefjord, Morgan, Tommaso, Paolo Di, Floden, Evan, Notredame, Cedric, Moreno, Pablo, Hellander, Andreas, Emami Khoonsari, Payam, Herman, Stephanie, Kultima, Kim, and Lampa, Samuel
- Abstract
Containers are gaining popularity in life science research as they provide a solution for encompassing dependencies of provisioned tools, simplify software installations for end users and offer a form of isolation between processes. Scientific workflows are ideal for chaining containers into data analysis pipelines to aid in creating reproducible analyses. In this article, we review a number of approaches to using containers as implemented in the workflow tools Nextflow, Galaxy, Pachyderm, Argo, Kubeflow, Luigi and SciPipe, when deployed in cloud environments. A particular focus is placed on the workflow tool’s interaction with the Kubernetes container orchestration framework.
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- 2021
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13. Metabolomics of Cerebrospinal Fluid from Healthy Subjects Reveal Metabolites Associated with Ageing
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Carlsson, Henrik, Rollborn, Niclas, Herman, Stephanie, Freyhult, Eva, Svenningsson, Anders, Burman, Joachim, Kultima, Kim, Carlsson, Henrik, Rollborn, Niclas, Herman, Stephanie, Freyhult, Eva, Svenningsson, Anders, Burman, Joachim, and Kultima, Kim
- Abstract
To increase our understanding of age-related diseases affecting the central nervous system (CNS) it is important to understand the molecular processes of biological ageing. Metabolomics of cerebrospinal fluid (CSF) is a promising methodology to increase our understanding of naturally occurring processes of ageing of the brain and CNS that could be reflected in CSF. In the present study the CSF metabolomes of healthy subjects aged 30-74 years (n = 23) were studied using liquid chromatography high-resolution mass spectrometry (LC-HRMS), and investigated in relation to age. Ten metabolites were identified with high confidence as significantly associated with ageing, eight with increasing levels with ageing: isoleucine, acetylcarnitine, pipecolate, methionine, glutarylcarnitine, 5-hydroxytryptophan, ketoleucine, and hippurate; and two decreasing with ageing: methylthioadenosine and 3-methyladenine. To our knowledge, this is the first time the CSF metabolomes of healthy subjects are assessed in relation to ageing. The present study contributes to the field of ageing metabolomics by presenting a number of metabolites present in CSF with potential relevance for ageing and the results motivate further studies.
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- 2021
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14. Approaches for containerized scientific workflows in cloud environments with applications in life science
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Spjuth, Ola, primary, Capuccini, Marco, additional, Carone, Matteo, additional, Larsson, Anders, additional, Schaal, Wesley, additional, Novella, Jon Ander, additional, Stein, Oliver, additional, Ekmefjord, Morgan, additional, Tommaso, Paolo Di, additional, Floden, Evan, additional, Notredame, Cedric, additional, Moreno, Pablo, additional, Hellander, Andreas, additional, Khoonsari, Payam Emami, additional, Herman, Stephanie, additional, Kultima, Kim, additional, and Lampa, Samuel, additional
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- 2021
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15. Towards an Earlier Detection of Progressive Multiple Sclerosis using Metabolomics and Machine Learning
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Herman, Stephanie
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progressive multiple sclerosis ,Bioinformatics (Computational Biology) ,machine learning ,Neurology ,Neurologi ,advanced analytics ,Bioinformatik (beräkningsbiologi) ,biomarkers ,bioinformatics ,metabolomics ,mass spectrometry - Abstract
Decision-making guided by advanced analytics is becoming increasingly common in many fields. Implementing computationally driven healthcare solutions does, however, pose ethical dilemmas as it involves human health. Therefore, augmenting clinical expertise with advanced analytical insights to support decision-making in healthcare is probably a more feasible strategy. Multiple sclerosis is a debilitating neurological disease with two subtypes; relapsing-remitting multiple sclerosis (RRMS) and the typically late-stage progressive subtype (PMS). Progressive multiple sclerosis is a neurodegenerative phenotype, with a vague functional definition, that currently is diagnosed retrospectively. The challenge of diagnosing PMS earlier is a great example where data-driven insights might prove useful. This thesis addresses the need for an earlier detection of patients developing the progressive and neurodegenerative subtype of multiple sclerosis, using primarily metabolomics and machine learning approaches. In Paper I, the biochemical differences in cerebrospinal fluid (CSF) from RRMS and PMS patients were characterised, leading to the conclusion that it is possible to distinguish PMS patients based on biochemical alterations. In addition, pathway analysis revealed several metabolic pathways that were affected in the transition to PMS, including tryptophan metabolism and pyrimidine metabolism. In Paper II and III, the possibility of generating a concise PMS signature based on solely low-molecular measurements (III) or in combination with radiological and protein measures (II) was explored. In both cases, it was concluded that it is plausible to generate a condensed set of highly informative markers that can distinguish PMS patients from RRMS patients. In Paper III, the classifier was complemented with conformal prediction that enabled an estimate of confidence in single patient predictions and a personalised evaluation of current disease state. Finally, in Paper IV, the extracted low-molecular marker candidates were characterised in isolation, revealing that several metabolites were distinctively altered in the CSF of PMS patients, including increased levels of 4-acetamidobutanoate, 4-hydroxybenzoate and thymine. Overall, the results from this work indicate that it is possible to detect PMS at an earlier stage and that advanced analytical algorithms can support healthcare.
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- 2020
16. Descriptive Proteome Analysis to Investigate Context-Dependent Treatment Responses to OXPHOS Inhibition in Colon Carcinoma Cells Grown as Monolayer and Multicellular Tumor Spheroids
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Steinmetz, Julia, Senkowski, Wojciech, Lengqvist, Johan, Rubin, Jenny, Ossipova, Elena, Herman, Stephanie, Larsson, Rolf, Jakobsson, Per-Johan, Fryknäs, Mårten, Kultima, Kim, Steinmetz, Julia, Senkowski, Wojciech, Lengqvist, Johan, Rubin, Jenny, Ossipova, Elena, Herman, Stephanie, Larsson, Rolf, Jakobsson, Per-Johan, Fryknäs, Mårten, and Kultima, Kim
- Abstract
We have previously identified selective upregulation of the mevalonate pathway genes upon inhibition of oxidative phosphorylation (OXPHOS) in quiescent cancer cells. Using mass spectrometry-based proteomics, we here investigated whether these responses are corroborated on the protein level and whether proteomics could yield unique insights into context-dependent biology. HCT116 colon carcinoma cells were cultured as monolayer cultures, proliferative multicellular tumor spheroids (P-MCTS), or quiescent (Q:MCTS) multicellular tumor spheroids and exposed to OXPHOS inhibitors: nitazoxanide, FCCP, oligomycin, and salinomycin or the HMG-CoA-reductase inhibitor simvastatin at two different doses for 6 and 24 h. Samples were processed using an in-depth bottom-up proteomics workflow resulting in a total of 9286 identified protein groups. Gene set enrichment analysis showed profound differences between the three cell systems and confirmed differential enrichment of hypoxia, OXPHOS, and cell cycle progression-related protein responses in P-MCTS and QMCTS. Treatment experiments showed that the observed drug-induced alterations in gene expression of metabolically challenged cells are not translated directly to the protein level, but the results reaffirmed OXPHOS as a selective vulnerability of quiescent cancer cells. This work provides rationale for the use of deep proteome profiling to identify context-dependent treatment responses and encourages further studies investigating metabolic processes that could be co-targeted together with OXPHOS to eradicate quiescent cancer cells.
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- 2020
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17. Urokinase, CX3CL1, CCL2, TRAIL and IL‐18 induced by interferon‐β treatment
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Zhukovsky, Christina, primary, Herman, Stephanie, additional, Wiberg, Anna, additional, Cunningham, Janet L., additional, Kultima, Kim, additional, and Burman, Joachim, additional
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- 2021
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18. Metabolomics of Cerebrospinal Fluid from Healthy Subjects Reveal Metabolites Associated with Ageing
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Carlsson, Henrik, primary, Rollborn, Niclas, additional, Herman, Stephanie, additional, Freyhult, Eva, additional, Svenningsson, Anders, additional, Burman, Joachim, additional, and Kultima, Kim, additional
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- 2021
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19. Descriptive Proteome Analysis to Investigate Context-Dependent Treatment Responses to OXPHOS Inhibition in Colon Carcinoma Cells Grown as Monolayer and Multicellular Tumor Spheroids
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Steinmetz, Julia, primary, Senkowski, Wojciech, additional, Lengqvist, Johan, additional, Rubin, Jenny, additional, Ossipova, Elena, additional, Herman, Stephanie, additional, Larsson, Rolf, additional, Jakobsson, Per-Johan, additional, Fryknäs, Mårten, additional, and Kultima, Kim, additional
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- 2020
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20. Approaches for Containerized Scientific Workflows in Cloud Environments with Applications in Life Science
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Spjuth, Ola, primary, Capuccini, Marco, additional, Carone, Matteo, additional, Larsson, Anders, additional, Schaal, Wesley, additional, Novella, Jon Ander, additional, Stein, Oliver, additional, Ekmefjord, Morgan, additional, Di Tommaso, Paolo, additional, Floden, Evan, additional, Notredame, Cedric, additional, Moreno, Pablo, additional, Emami Khoonsari, Payam, additional, Herman, Stephanie, additional, Kultima, Kim, additional, and Lampa, Samuel, additional
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- 2020
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21. The voices of children: preadolescent children's experiences in family therapy
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Stith, Sandra M., Rosen, Karen H., McCollum, Eric E., Coleman, Jean U., and Herman, Stephanie A.
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Family psychotherapy -- Research ,Children -- Psychological aspects ,Family and marriage - Published
- 1996
22. Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing-Remitting Multiple Sclerosis
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Herman, Stephanie, Åkerfeldt, Torbjörn, Spjuth, Ola, Burman, Joachim, Kultima, Kim, Herman, Stephanie, Åkerfeldt, Torbjörn, Spjuth, Ola, Burman, Joachim, and Kultima, Kim
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To better understand the pathophysiological differences between secondary progressive multiple sclerosis (SPMS) and relapsing-remitting multiple sclerosis (RRMS), and to identify potential biomarkers of disease progression, we applied high-resolution mass spectrometry (HRMS) to investigate the metabolome of cerebrospinal fluid (CSF). The biochemical differences were determined using partial least squares discriminant analysis (PLS-DA) and connected to biochemical pathways as well as associated to clinical and radiological measures. Tryptophan metabolism was significantly altered, with perturbed levels of kynurenate, 5-hydroxytryptophan, 5-hydroxyindoleacetate, and N-acetylserotonin in SPMS patients compared with RRMS and controls. SPMS patients had altered kynurenine compared with RRMS patients, and altered indole-3-acetate compared with controls. Regarding the pyrimidine metabolism, SPMS patients had altered levels of uridine and deoxyuridine compared with RRMS and controls, and altered thymine and glutamine compared with RRMS patients. Metabolites from the pyrimidine metabolism were significantly associated with disability, disease activity and brain atrophy, making them of particular interest for understanding the disease mechanisms and as markers of disease progression. Overall, these findings are of importance for the characterization of the molecular pathogenesis of SPMS and support the hypothesis that the CSF metabolome may be used to explore changes that occur in the transition between the RRMS and SPMS pathologies.
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- 2019
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23. PhenoMeNal : Processing and analysis of metabolomics data in the cloud
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Peters, Kristian, Bradbury, James, Bergmann, Sven, Capuccini, Marco, Cascante, Marta, de Atauri, Pedro, Ebbels, Timothy M. D., Foguet, Carles, Glen, Robert, Gonzalez-Beltran, Alejandra, Günther, Ulrich L., Handakas, Evangelos, Hankemeier, Thomas, Haug, Kenneth, Herman, Stephanie, Holub, Petr, Izzo, Massimiliano, Jacob, Daniel, Johnson, David, Jourdan, Fabien, Kale, Namrata, Karaman, Ibrahim, Khalili, Bita, Emami Khoonsari, Payam, Kultima, Kim, Lampa, Samuel, Larsson, Anders, Ludwig, Christian, Moreno, Pablo, Neumann, Steffen, Novella, Jon Ander, O'Donovan, Claire, Pearce, Jake T. M., Peluso, Alina, Piras, Marco Enrico, Pireddu, Luca, Reed, Michelle A. C., Rocca-Serra, Philippe, Roger, Pierrick, Rosato, Antonio, Rueedi, Rico, Ruttkies, Christoph, Sadawi, Noureddin, Salek, Reza M., Sansone, Susanna-Assunta, Selivanov, Vitaly, Spjuth, Ola, Schober, Daniel, Thévenot, Etienne A., Tomasoni, Mattia, van Rijswijk, Merlijn, van Vliet, Michael, Viant, Mark R., Weber, Ralf J. M., Zanetti, Gianluigi, Steinbeck, Christoph, Peters, Kristian, Bradbury, James, Bergmann, Sven, Capuccini, Marco, Cascante, Marta, de Atauri, Pedro, Ebbels, Timothy M. D., Foguet, Carles, Glen, Robert, Gonzalez-Beltran, Alejandra, Günther, Ulrich L., Handakas, Evangelos, Hankemeier, Thomas, Haug, Kenneth, Herman, Stephanie, Holub, Petr, Izzo, Massimiliano, Jacob, Daniel, Johnson, David, Jourdan, Fabien, Kale, Namrata, Karaman, Ibrahim, Khalili, Bita, Emami Khoonsari, Payam, Kultima, Kim, Lampa, Samuel, Larsson, Anders, Ludwig, Christian, Moreno, Pablo, Neumann, Steffen, Novella, Jon Ander, O'Donovan, Claire, Pearce, Jake T. M., Peluso, Alina, Piras, Marco Enrico, Pireddu, Luca, Reed, Michelle A. C., Rocca-Serra, Philippe, Roger, Pierrick, Rosato, Antonio, Rueedi, Rico, Ruttkies, Christoph, Sadawi, Noureddin, Salek, Reza M., Sansone, Susanna-Assunta, Selivanov, Vitaly, Spjuth, Ola, Schober, Daniel, Thévenot, Etienne A., Tomasoni, Mattia, van Rijswijk, Merlijn, van Vliet, Michael, Viant, Mark R., Weber, Ralf J. M., Zanetti, Gianluigi, and Steinbeck, Christoph
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- 2019
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24. Container-based bioinformatics with Pachyderm
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Novella, Jon Ander, Emami Khoonsari, Payam, Herman, Stephanie, Whitenack, Daniel, Capuccini, Marco, Burman, Joachim, Kultima, Kim, Spjuth, Ola, Novella, Jon Ander, Emami Khoonsari, Payam, Herman, Stephanie, Whitenack, Daniel, Capuccini, Marco, Burman, Joachim, Kultima, Kim, and Spjuth, Ola
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eSSENCE
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- 2019
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25. Interoperable and scalable data analysis with microservices : Applications in metabolomics
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Emami Khoonsari, Payam, Moreno, Pablo, Bergmann, Sven, Burman, Joachim, Capuccini, Marco, Carone, Matteo, Cascante, Marta, de Atauri, Pedro, Foguet, Carles, Gonzalez-Beltran, Alejandra N., Hankemeier, Thomas, Haug, Kenneth, He, Sijin, Herman, Stephanie, Johnson, David, Kale, Namrata, Larsson, Anders, Neumann, Steffen, Peters, Kristian, Pireddu, Luca, Rocca-Serra, Philippe, Roger, Pierrick, Rueedi, Rico, Ruttkies, Christoph, Sadawi, Noureddin, Salek, Reza M., Sansone, Susanna-Assunta, Schober, Daniel, Selivanov, Vitaly, Thévenot, Etienne A., van Vliet, Michael, Zanetti, Gianluigi, Steinbeck, Christoph, Kultima, Kim, Spjuth, Ola, Emami Khoonsari, Payam, Moreno, Pablo, Bergmann, Sven, Burman, Joachim, Capuccini, Marco, Carone, Matteo, Cascante, Marta, de Atauri, Pedro, Foguet, Carles, Gonzalez-Beltran, Alejandra N., Hankemeier, Thomas, Haug, Kenneth, He, Sijin, Herman, Stephanie, Johnson, David, Kale, Namrata, Larsson, Anders, Neumann, Steffen, Peters, Kristian, Pireddu, Luca, Rocca-Serra, Philippe, Roger, Pierrick, Rueedi, Rico, Ruttkies, Christoph, Sadawi, Noureddin, Salek, Reza M., Sansone, Susanna-Assunta, Schober, Daniel, Selivanov, Vitaly, Thévenot, Etienne A., van Vliet, Michael, Zanetti, Gianluigi, Steinbeck, Christoph, Kultima, Kim, and Spjuth, Ola
- Abstract
Motivation Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator. Results We developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science., Title in thesis list of papers: Interoperable and scalable metabolomics data analysis with microservices
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- 2019
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26. Systematic Analysis of the Cerebrospinal Fluid Proteome of Fibromyalgia patients
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Emami Khoonsari, Payam, Musunri, Sravani, Herman, Stephanie, Svensson, Camilla I, Tanum, Lars, Gordh, Torsten, Kultima, Kim, Emami Khoonsari, Payam, Musunri, Sravani, Herman, Stephanie, Svensson, Camilla I, Tanum, Lars, Gordh, Torsten, and Kultima, Kim
- Abstract
Fibromyalgia (FM) is a syndrome characterized by widespread muscular pain, fatigue and functional symptoms, which is known to be difficult to diagnose as the various symptoms overlap with many other conditions. Currently, there are no biomarkers for FM, and the diagnosis is made subjectively by the clinicians. We have performed shotgun proteomics on cerebrospinal fluid (CSF) from FM patients and non-pain controls to find potential biomarker candidates for this syndrome. Based on our multivariate and univariate analyses, we found that the relative differences in the CSF proteome between FM patients and controls were moderate. Four proteins, important to discriminate FM patients from non-pain controls, were found: Apolipoprotein C-III, Galectin-3-binding protein, Malate dehydrogenase cytoplasmic and the neuropeptide precursor protein ProSAAS. These proteins are involved in lipoprotein lipase (LPL) activity, inflammatory signaling, energy metabolism and neuropeptide signaling.
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- 2019
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27. Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers
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Emami Khoonsari, Payam, Shevchenko, Ganna, Herman, Stephanie, Remnestal, Julia, Giedraitis, Vilmantas, Brundin, RoseMarie, Degerman Gunnarsson, Malin, Kilander, Lena, Zetterberge, Henrik, Nilsson, Peter, Lannfelt, Lars, Ingelsson, Martin, Kultima, Kim, Emami Khoonsari, Payam, Shevchenko, Ganna, Herman, Stephanie, Remnestal, Julia, Giedraitis, Vilmantas, Brundin, RoseMarie, Degerman Gunnarsson, Malin, Kilander, Lena, Zetterberge, Henrik, Nilsson, Peter, Lannfelt, Lars, Ingelsson, Martin, and Kultima, Kim
- Abstract
Background: Alzheimer’s disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD. Objective: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects. Methods: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (n = 206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4–9 years and 21 of these converted to AD, whereas 53 remained stable. Results: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCI/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively. Conclusions: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects.
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- 2019
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28. Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers
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Khoonsari, Payam Emami, Shevchenko, Ganna, Herman, Stephanie, Remnestål, Julia, Giedraitis, Vilmantas, Brundin, RoseMarie, Gunnarsson, Malin Degerman, Kilander, Lena, Zetterberge, Henrik, Nilsson, Peter, Lannfelt, Lars, Ingelsson, Martin, Kultima, Kim, Khoonsari, Payam Emami, Shevchenko, Ganna, Herman, Stephanie, Remnestål, Julia, Giedraitis, Vilmantas, Brundin, RoseMarie, Gunnarsson, Malin Degerman, Kilander, Lena, Zetterberge, Henrik, Nilsson, Peter, Lannfelt, Lars, Ingelsson, Martin, and Kultima, Kim
- Abstract
Background: Alzheimer's disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: A beta(42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD. Objective: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects. Methods: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (n = 206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4-9 years and 21 of these converted to AD, whereas 53 remained stable. Results: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCl/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively. Conclusions: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects., QC 20190312
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- 2019
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29. Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis
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Herman, Stephanie, Emami Khoonsari, Payam, Tolf, Andreas, Steinmetz, Julia, Zetterberg, Henrik, Åkerfeldt, Torbjörn, Jakobsson, Per-Johan, Larsson, Anders, Spjuth, Ola, Burman, Joachim, and Kultima, Kim
- Subjects
disease progression ,Neurology ,Neurologi ,biomarker ,multiple sclerosis ,data integration ,metabolomics - Abstract
Molecular networks in neurological diseases are complex. Despite this fact, contemporary biomarkers are in most cases interpreted in isolation, leading to a significant loss of information and power. We present an analytical approach to scrutinize and combine information from biomarkers originating from multiple sources with the aim of discovering a condensed set of biomarkers that in combination could distinguish the progressive degenerative phenotype of multiple sclerosis (SPMS) from the relapsing-remitting phenotype (RRMS). Methods: Clinical and magnetic resonance imaging (MRI) data were integrated with data from protein and metabolite measurements of cerebrospinal fluid, and a method was developed to sift through all the variables to establish a small set of highly informative measurements. This prospective study included 16 SPMS patients, 30 RRMS patients and 10 controls. Protein concentrations were quantitated with multiplexed fluorescent bead-based immunoassays and ELISA. The metabolome was recorded using liquid chromatography-mass spectrometry. Clinical follow-up data of the SPMS patients were used to assess disease progression and development of disability. Results: Eleven variables were in combination able to distinguish SPMS from RRMS patients with high confidence superior to any single measurement. The identified variables consisted of three MRI variables: the size of the spinal cord and the third ventricle and the total number of T1 hypointense lesions; six proteins: galectin-9, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor alpha (TGF-α), tumor necrosis factor alpha (TNF-α), soluble CD40L (sCD40L) and platelet-derived growth factor AA (PDGF-AA); and two metabolites: 20β-dihydrocortisol (20β-DHF) and indolepyruvate. The proteins myelin basic protein (MBP) and macrophage-derived chemokine (MDC), as well as the metabolites 20β-DHF and 5,6-dihydroxyprostaglandin F1a (5,6-DH-PGF1), were identified as potential biomarkers of disability progression. Conclusion: Our study demonstrates, in a limited but well-defined and data-rich cohort, the importance and value of combining multiple biomarkers to aid diagnostics and track disease progression.
- Published
- 2018
30. Interoperable and scalable data analysis with microservices: applications in metabolomics
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Emami Khoonsari, Payam, primary, Moreno, Pablo, additional, Bergmann, Sven, additional, Burman, Joachim, additional, Capuccini, Marco, additional, Carone, Matteo, additional, Cascante, Marta, additional, de Atauri, Pedro, additional, Foguet, Carles, additional, Gonzalez-Beltran, Alejandra N, additional, Hankemeier, Thomas, additional, Haug, Kenneth, additional, He, Sijin, additional, Herman, Stephanie, additional, Johnson, David, additional, Kale, Namrata, additional, Larsson, Anders, additional, Neumann, Steffen, additional, Peters, Kristian, additional, Pireddu, Luca, additional, Rocca-Serra, Philippe, additional, Roger, Pierrick, additional, Rueedi, Rico, additional, Ruttkies, Christoph, additional, Sadawi, Noureddin, additional, Salek, Reza M, additional, Sansone, Susanna-Assunta, additional, Schober, Daniel, additional, Selivanov, Vitaly, additional, Thévenot, Etienne A, additional, van Vliet, Michael, additional, Zanetti, Gianluigi, additional, Steinbeck, Christoph, additional, Kultima, Kim, additional, and Spjuth, Ola, additional
- Published
- 2019
- Full Text
- View/download PDF
31. Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis
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Herman, Stephanie, primary, Åkerfeldt, Torbjörn, additional, Spjuth, Ola, additional, Burman, Joachim, additional, and Kultima, Kim, additional
- Published
- 2019
- Full Text
- View/download PDF
32. Improved Differential Diagnosis of Alzheimer’s Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers
- Author
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Khoonsari, Payam Emami, primary, Shevchenko, Ganna, additional, Herman, Stephanie, additional, Remnestål, Julia, additional, Giedraitis, Vilmantas, additional, Brundin, RoseMarie, additional, Degerman Gunnarsson, Malin, additional, Kilander, Lena, additional, Zetterberg, Henrik, additional, Nilsson, Peter, additional, Lannfelt, Lars, additional, Ingelsson, Martin, additional, and Kultima, Kim, additional
- Published
- 2019
- Full Text
- View/download PDF
33. PhenoMeNal: processing and analysis of metabolomics data in the cloud
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Peters, Kristian, primary, Bradbury, James, additional, Bergmann, Sven, additional, Capuccini, Marco, additional, Cascante, Marta, additional, de Atauri, Pedro, additional, Ebbels, Timothy M D, additional, Foguet, Carles, additional, Glen, Robert, additional, Gonzalez-Beltran, Alejandra, additional, Günther, Ulrich L, additional, Handakas, Evangelos, additional, Hankemeier, Thomas, additional, Haug, Kenneth, additional, Herman, Stephanie, additional, Holub, Petr, additional, Izzo, Massimiliano, additional, Jacob, Daniel, additional, Johnson, David, additional, Jourdan, Fabien, additional, Kale, Namrata, additional, Karaman, Ibrahim, additional, Khalili, Bita, additional, Emami Khonsari, Payam, additional, Kultima, Kim, additional, Lampa, Samuel, additional, Larsson, Anders, additional, Ludwig, Christian, additional, Moreno, Pablo, additional, Neumann, Steffen, additional, Novella, Jon Ander, additional, O'Donovan, Claire, additional, Pearce, Jake T M, additional, Peluso, Alina, additional, Piras, Marco Enrico, additional, Pireddu, Luca, additional, Reed, Michelle A C, additional, Rocca-Serra, Philippe, additional, Roger, Pierrick, additional, Rosato, Antonio, additional, Rueedi, Rico, additional, Ruttkies, Christoph, additional, Sadawi, Noureddin, additional, Salek, Reza M, additional, Sansone, Susanna-Assunta, additional, Selivanov, Vitaly, additional, Spjuth, Ola, additional, Schober, Daniel, additional, Thévenot, Etienne A, additional, Tomasoni, Mattia, additional, van Rijswijk, Merlijn, additional, van Vliet, Michael, additional, Viant, Mark R, additional, Weber, Ralf J M, additional, Zanetti, Gianluigi, additional, and Steinbeck, Christoph, additional
- Published
- 2018
- Full Text
- View/download PDF
34. Effect of acute muscle contusion injury, with and without dietary fish oil, on adult and aged male rats: contractile and biochemical responses
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Russ, David W., primary, Garvey, Sean M., additional, Densmore, Clay, additional, Hawks, Trevor, additional, Herman, Stephanie, additional, and Pardi, Katherine, additional
- Published
- 2018
- Full Text
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35. Approaches for containerized scientific workflows in cloud environments with applications in life science
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Spjuth, Ola, primary, Capuccini, Marco, additional, Carone, Matteo, additional, Larsson, Anders, additional, Schaal, Wesley, additional, Novella, Jon, additional, Di Tommaso, Paolo, additional, Notredame, Cedric, additional, Moreno, Pablo, additional, Khoonsari, Payam E, additional, Herman, Stephanie, additional, Kultima, Kim, additional, and Lampa, Samuel, additional
- Published
- 2018
- Full Text
- View/download PDF
36. Container-based bioinformatics with Pachyderm
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Novella, Jon Ander, primary, Emami Khoonsari, Payam, additional, Herman, Stephanie, additional, Whitenack, Daniel, additional, Capuccini, Marco, additional, Burman, Joachim, additional, Kultima, Kim, additional, and Spjuth, Ola, additional
- Published
- 2018
- Full Text
- View/download PDF
37. Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis
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Herman, Stephanie, primary, Khoonsari, Payam Emami, additional, Tolf, Andreas, additional, Steinmetz, Julia, additional, Zetterberg, Henrik, additional, Åkerfeldt, Torbjörn, additional, Jakobsson, Per-Johan, additional, Larsson, Anders, additional, Spjuth, Ola, additional, Burman, Joachim, additional, and Kultima, Kim, additional
- Published
- 2018
- Full Text
- View/download PDF
38. Automatic detection of protein degradation markers in mass spectrometry imaging
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Herman, Stephanie
- Subjects
Mice ,Bioinformatics (Computational Biology) ,Imaging Mass Spectrometry ,Heat Stabilization ,Protein Degradation ,Bioinformatik (beräkningsbiologi) ,Matrix-Assisted Laser Desorption-Ionization ,Brain ,Image Analysis - Abstract
Today we are collecting a large amount of tissue samples to store for future studies of different health conditions, in hopes that the focus in health care will shift from treatments to early detection and prevention, by the use of biomarkers. To make sure that the storing of tissue is done in a reliable way, where the molecular profile of the samples are preserved, we first need to characterise how these changes occur. In this thesis, data from mice brains were collected using MALDI imaging mass spectrometry (IMS) and an analysis pipeline for robust MALDI IMS data handling and evaluation was implemented. The finished pipeline contains two reduction algorithms, catching images with interesting intensity features, while taking the spatial information into account, along with a robust similarity measurement, for measuring the degree of co-localisation. It also includes a clustering algorithm built upon the similarity measurement and an amino acid mass comparer, iteratively generating combinations of amino acids for further mass comparisons with mass differences between cluster members. Availability: The source code is available at https://github.com/stephanieherman/thesis
- Published
- 2016
39. Interoperable and scalable data analysis with microservices: Applications in Metabolomics
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Emami Khoonsari, Payam, primary, Moreno, Pablo, additional, Bergmann, Sven, additional, Burman, Joachim, additional, Capuccini, Marco, additional, Carone, Matteo, additional, Cascante, Marta, additional, de Atauri, Pedro, additional, Foguet, Carles, additional, Gonzalez-Beltran, Alejandra, additional, Hankemeier, Thomas, additional, Haug, Kenneth, additional, He, Sijin, additional, Herman, Stephanie, additional, Johnson, David, additional, Kale, Namrata, additional, Larsson, Anders, additional, Neumann, Steffen, additional, Peters, Kristian, additional, Pireddu, Luca, additional, Rocca-Serra, Philippe, additional, Roger, Pierrick, additional, Rueedi, Rico, additional, Ruttkies, Christoph, additional, Sadawi, Noureddin, additional, Salek, Reza M., additional, Sansone, Susanna-Assunta, additional, Schober, Daniel, additional, Selivanov, Vitaly, additional, Thévenot, Etienne A., additional, van Vliet, Michael, additional, Zanetti, Gianluigi, additional, Steinbeck, Christoph, additional, Kultima, Kim, additional, and Spjuth, Ola, additional
- Published
- 2017
- Full Text
- View/download PDF
40. Interoperable and scalable data analysis with microservices: applications in metabolomics.
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Khoonsari, Payam Emami, Moreno, Pablo, Bergmann, Sven, Burman, Joachim, Capuccini, Marco, Carone, Matteo, Cascante, Marta, Atauri, Pedro de, Foguet, Carles, Gonzalez-Beltran, Alejandra N, Hankemeier, Thomas, Haug, Kenneth, He, Sijin, Herman, Stephanie, Johnson, David, Kale, Namrata, Larsson, Anders, Neumann, Steffen, Peters, Kristian, and Pireddu, Luca
- Subjects
INTERNET servers ,NUCLEAR magnetic resonance spectroscopy ,DATA analysis ,WEB portals ,SOURCE code ,VIRTUAL reality - Abstract
Motivation Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator. Results We developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science. Availability and implementation The PhenoMeNal consortium maintains a web portal (https://portal.phenomenal-h2020.eu) providing a GUI for launching the Virtual Research Environment. The GitHub repository https://github.com/phnmnl/ hosts the source code of all projects. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
41. A probability-based quality measure improves the classification of unexpected sequences in in situ sequencing
- Author
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Nordesjö, Olle, Pontén, Victor, Herman, Stephanie, Ås, Joel, Jamal, Sabri, and Nyberg, Alona
- Subjects
bildanalys ,Diagnostic Biotechnology ,Bioengineering Equipment ,Bioinformatics (Computational Biology) ,fluorescence in situ sequencing ,Bioinformatics and Systems Biology ,Medicinsk bildbehandling ,molecular inversion probe ,Bioteknisk apparatteknik ,Signalbehandling ,quality assurance ,bioinformatics ,Bioinformatik och systembiologi ,bioinformatik ,padlock probe ,Medical Image Processing ,Diagnostisk bioteknologi ,image analysis ,Signal Processing ,Bioinformatik (beräkningsbiologi) ,in situ sekvensering ,molekylär inversionsprob ,kvalitetskontroll - Abstract
In situ sekvensering är en metod som kan användas för att lokalisera differentiellt uttryck av mRNA direkt i vävnadssnitt, vilket kan ge viktiga ledtrådar om många sjukdomstillstånd. Idag förloras många av sekvenserna från in situ sekvensering på grund av det kvalitetsmått man använder för att säkerställa att sekvenser är korrekta. Det finns troligtvis möjlighet att förbättra prestandan av den nuvarande base calling-metoden eftersom att metoden är i ett tidigt utvecklingsskede. Vi har genomfört explorativ dataanalys för att undersöka förekomst av systematiska fel och korrigerat för dessa med hjälp av statistiska metoder. Vi har framförallt undersökt tre metoder för att korrigera för systematiska fel: I) Korrektion av överblödning som sker på grund avöverlappande emissionsspektra mellan fluorescenta prober. II) En sannolikhetsbaserad tolkningav intensitetsdata som resulterar i ett nytt kvalitetsmått och en alternativ klassificerare baseradpå övervakad inlärning. III) En utredning om förekomst av cykelberoende effekter, exempelvisofullständig dehybridisering av fluorescenta prober. Vi föreslår att man gör följande saker: Implementerar och utvärderar det sannolikhetsbaserade kvalitetsmåttet Utvecklar och implementerar den föreslagna klassificeraren Genomför ytterligare experiment för att påvisa eller bestrida förekomst av ofullständigdehybridisering In situ sequencing is a method that can be used to localize differential expression of mRNA directly in tissue sections, something that can give valuable insights to many statest of disease. Today, many of the registered sequences from in situ sequencing are lost due to a conservative quality measure used to filter out incorrect sequencing reads. There is room for improvement in the performance of the current method for base calling since the technology is in an early stage of development. We have performed exploratory data analysis to investigate occurrence of systematic errors, and corrected for these by using various statistical methods. The primary methods that have been investigated are the following: I) Correction of emission spectra overlap resulting in spillover between channels. II) A probability-based interpretation of intensity data, resulting in a novel quality measure and an alternative classifier based on supervised learning. III) Analysis of occurrence of cycle dependent effects, e.g. incomplete dehybridization of fluorescent probes. We suggest the following: Implementation and evaluation of the probability-based quality measure Development and implementation of the proposed classifier Additional experiments to investigate the possible occurrence of incomplete dehybridization
- Published
- 2014
42. Alternative Gavage Diet for Piscivores
- Author
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Herman, Stephanie, primary
- Published
- 2016
- Full Text
- View/download PDF
43. Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers.
- Author
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Nielsen, Henrietta, Khoonsari, Payam Emami, Herman, Stephanie, Kultima, Kim, Shevchenko, Ganna, Remnestål, Julia, Nilsson, Peter, Giedraitis, Vilmantas, Brundin, RoseMarie, Degerman Gunnarsson, Malin, Kilander, Lena, Lannfelt, Lars, Ingelsson, Martin, Gunnarsson, Malin Degerman, and Zetterberg, Henrik
- Abstract
Background: Alzheimer's disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD.Objective: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects.Methods: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (n = 206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4-9 years and 21 of these converted to AD, whereas 53 remained stable.Results: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCI/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively.Conclusions: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
44. Ett sannolikhetsbaserat kvalitetsmått förbättrar klassificeringen av oförväntade sekvenser i in situ sekvensering
- Author
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Nordesjö, Olle, Pontén, Victor, Herman, Stephanie, Ås, Joel, Jamal, Sabri, Nyberg, Alona, Nordesjö, Olle, Pontén, Victor, Herman, Stephanie, Ås, Joel, Jamal, Sabri, and Nyberg, Alona
- Abstract
In situ sekvensering är en metod som kan användas för att lokalisera differentiellt uttryck av mRNA direkt i vävnadssnitt, vilket kan ge viktiga ledtrådar om många sjukdomstillstånd. Idag förloras många av sekvenserna från in situ sekvensering på grund av det kvalitetsmått man använder för att säkerställa att sekvenser är korrekta. Det finns troligtvis möjlighet att förbättra prestandan av den nuvarande base calling-metoden eftersom att metoden är i ett tidigt utvecklingsskede. Vi har genomfört explorativ dataanalys för att undersöka förekomst av systematiska fel och korrigerat för dessa med hjälp av statistiska metoder. Vi har framförallt undersökt tre metoder för att korrigera för systematiska fel: I) Korrektion av överblödning som sker på grund avöverlappande emissionsspektra mellan fluorescenta prober. II) En sannolikhetsbaserad tolkningav intensitetsdata som resulterar i ett nytt kvalitetsmått och en alternativ klassificerare baseradpå övervakad inlärning. III) En utredning om förekomst av cykelberoende effekter, exempelvisofullständig dehybridisering av fluorescenta prober. Vi föreslår att man gör följande saker: Implementerar och utvärderar det sannolikhetsbaserade kvalitetsmåttet Utvecklar och implementerar den föreslagna klassificeraren Genomför ytterligare experiment för att påvisa eller bestrida förekomst av ofullständigdehybridisering, In situ sequencing is a method that can be used to localize differential expression of mRNA directly in tissue sections, something that can give valuable insights to many statest of disease. Today, many of the registered sequences from in situ sequencing are lost due to a conservative quality measure used to filter out incorrect sequencing reads. There is room for improvement in the performance of the current method for base calling since the technology is in an early stage of development. We have performed exploratory data analysis to investigate occurrence of systematic errors, and corrected for these by using various statistical methods. The primary methods that have been investigated are the following: I) Correction of emission spectra overlap resulting in spillover between channels. II) A probability-based interpretation of intensity data, resulting in a novel quality measure and an alternative classifier based on supervised learning. III) Analysis of occurrence of cycle dependent effects, e.g. incomplete dehybridization of fluorescent probes. We suggest the following: Implementation and evaluation of the probability-based quality measure Development and implementation of the proposed classifier Additional experiments to investigate the possible occurrence of incomplete dehybridization
- Published
- 2014
45. Journal of Marital and Family Therapy
- Author
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Smith, Sandra M., Rosen, Karen H., McCollum, Eric E., Coleman, Jean U., and Herman, Stephanie A.
- Subjects
Family psychotherapy -- Methods ,Psychotherapy -- Research ,Children -- Beliefs, opinions and attitudes ,Family and marriage ,Psychology and mental health - Abstract
Children in families undergoing family therapy want to be a part of the therapeutic process. All, with the exception of the youngest children, understood the objectives of therapy. They considered play an essential part of therapy and expressed preferences for certain traits and characteristics of therapists. Findings of a study on preadolescent children's experiences with family therapy also indicated the importance of action-oriented techniques.
- Published
- 1997
46. A service-learning program for computer science and software engineering
- Author
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Linos, Panagiotis K., primary, Herman, Stephanie, additional, and Lally, Julie, additional
- Published
- 2003
- Full Text
- View/download PDF
47. Find it, feel it, move it: help participants connect with their bodies during the warm-up
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Herman, Stephanie
- Subjects
Exercise -- Methods ,Abdomen -- Muscles ,Abdomen -- Physiological aspects ,Human mechanics ,Health ,Sports and fitness - Published
- 2008
48. Sinking in sand: center yourself before leading others in a guided relaxation
- Author
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Herman, Stephanie
- Subjects
Respiration -- Health aspects -- Analysis ,Relaxation -- Analysis -- Health aspects ,Meditation -- Analysis -- Health aspects ,Health ,Sports and fitness - Abstract
Each time you use your talent and abilities to guide clients in a scripted relaxation, you harness the power and privilege of being an agent of change. You are in [...]
- Published
- 2007
49. PhenoMeNal: processing and analysis of metabolomics data in the cloud
- Author
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Peters, Kristian, Bradbury, James, Bergmann, Sven, Capuccini, Marco, Cascante i Serratosa, Marta, Atauri Carulla, Ramón de, Ebbels, Timothy M.D., Foguet Coll, Carles, Glen, Robert, Gonzalez-Beltran, Alejandra, Günther, Ulrich L., Handakas, Evangelos, Hankemeier, Thomas, Haug, Kenneth, Herman, Stephanie, Holub, Petr, Izzo, Massimialiano, Jacob, Daniel, Johnson, David, Jourdan, Fabien, Kale, Namrata, Karaman, Ibrahim, Khalili, Bita, Emami Khonsari, Payam, Kultima, Kim, Lampa, Samuel, Larsson, Aanders, Ludwig, Christian, Moreno, Pablo, Neumann, Steffen, Novella, Jon Ander, O'Donovan, Claire, Pearce, Jake T.M., Peluso, Alina, Piras, Marco Enrico, Pireddu, Luca, Reed, Michelle A. C., Rocca-Serra, Philippe, Roger, Pierrick, Rosato, Antonio, and Universitat de Barcelona
- Subjects
Metabolòmica ,Bioinformàtica ,Bioinformatics ,Metabolomics - Abstract
BACKGROUND: Metabolomics is the comprehensive study of a multitude of small molecules to gain insight into an organism's metabolism. The research field is dynamic and expanding with applications across biomedical, biotechnological, and many other applied biological domains. Its computationally intensive nature has driven requirements for open data formats, data repositories, and data analysis tools. However, the rapid progress has resulted in a mosaic of independent, and sometimes incompatible, analysis methods that are difficult to connect into a useful and complete data analysis solution. FINDINGS: PhenoMeNal (Phenome and Metabolome aNalysis) is an advanced and complete solution to set up Infrastructure-as-a-Service (IaaS) that brings workflow-oriented, interoperable metabolomics data analysis platforms into the cloud. PhenoMeNal seamlessly integrates a wide array of existing open-source tools that are tested and packaged as Docker containers through the project's continuous integration process and deployed based on a kubernetes orchestration framework. It also provides a number of standardized, automated, and published analysis workflows in the user interfaces Galaxy, Jupyter, Luigi, and Pachyderm. CONCLUSIONS: PhenoMeNal constitutes a keystone solution in cloud e-infrastructures available for metabolomics. PhenoMeNal is a unique and complete solution for setting up cloud e-infrastructures through easy-to-use web interfaces that can be scaled to any custom public and private cloud environment. By harmonizing and automating software installation and configuration and through ready-to-use scientific workflow user interfaces, PhenoMeNal has succeeded in providing scientists with workflow-driven, reproducible, and shareable metabolomics data analysis platforms that are interfaced through standard data formats, representative datasets, versioned, and have been tested for reproducibility and interoperability. The elastic implementation of PhenoMeNal further allows easy adaptation of the infrastructure to other application areas and 'omics research domains.
50. A biochemical signature of progressive multiple sclerosis
- Author
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Herman, Stephanie, Emami Khoonsari, Payam, Bergman, Joakim, Svenningsson, Anders, Spjuth, Ola, Burman, Joachim, Kultima, Kim, Herman, Stephanie, Emami Khoonsari, Payam, Bergman, Joakim, Svenningsson, Anders, Spjuth, Ola, Burman, Joachim, and Kultima, Kim
- Abstract
Currently, very few treatments for patients in the progressive phases of multiple sclerosis (PMS) are available. To enable sensitive evaluation of future treatments, prognostic and predictive markers for therapeutic response are needed, as well as robust markers for early detection of PMS. We have previously demonstrated that a signature of 28 cerebrospinal fluid (CSF) biochemical markers could distinguish PMS from relapsing-remitting multiple sclerosis (RRMS) patients. Herein, we aimed to characterize the 28 previously extracted metabolites by assessing independent differences between 35 PMS and 35 RRMS patients as well as 49 healthy control subjects. Twenty-two of the PMS patients were part of a controlled clinical trial evaluating the effect of intrathecal rituximab for PMS. Using follow-up assessments, we related the metabolites to clinical outcomes of the trial and investigated if they could predict a poor or beneficial treatment response. Finally, we investigated the metabolites’ associations to a panel of six CSF protein biomarkers of axonal, myelin and astrocyte damage as well as T- and B- cell activation and differentiation. The composite signature was predominantly classifying patients as having a poor treatment outcome, achieving an estimated area under the curve (AUC) of 0.63 (sensitivity = 0.90, specificity = 0.38). Univariately, C4H6N6O4 and phenolic phosphate were significantly (p-value<0.05) increased in patients with a poor outcome. We also demonstrated that a majority (n=22) of the metabolites showed PMS distinctive alterations, including increased CSF levels of 4-acetamidobutanoate, 4-hydroxybenzoate and thymine. 4-Acetamidobutanoate did also display significant associations with the results from the symbol digit modalities test (SDMT) and the 9-hole peg test (9-HPT) using the dominant hand, and the protein markers myelin basic protein (MBP), neurofilament light (NFL) and glial fibrillary acidic protein (GFAp), whereas 4-hydroxybenzoate display
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