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3. Transcript- and annotation-guided genome assembly of the European starling

Author

Stuart, KC, Edwards, RJ ; https://orcid.org/0000-0002-3645-5539, Cheng, Y, Warren, WC, Burt, DW, Sherwin, WB ; https://orcid.org/0000-0002-1578-8473, Hofmeister, NR, Werner, SJ, Ball, GF, Bateson, M, Brandley, MC, Buchanan, KL, Cassey, P, Clayton, DF, De Meyer, T, Meddle, SL, Rollins, LA ; https://orcid.org/0000-0002-3279-7005, Stuart, KC, Edwards, RJ ; https://orcid.org/0000-0002-3645-5539, Cheng, Y, Warren, WC, Burt, DW, Sherwin, WB ; https://orcid.org/0000-0002-1578-8473, Hofmeister, NR, Werner, SJ, Ball, GF, Bateson, M, Brandley, MC, Buchanan, KL, Cassey, P, Clayton, DF, De Meyer, T, Meddle, SL, and Rollins, LA ; https://orcid.org/0000-0002-3279-7005

Abstract

The European starling, Sturnus vulgaris, is an ecologically significant, globally invasive avian species that is also suffering from a major decline in its native range. Here, we present the genome assembly and long-read transcriptome of an Australian-sourced European starling (S. vulgaris vAU), and a second, North American, short-read genome assembly (S. vulgaris vNA), as complementary reference genomes for population genetic and evolutionary characterization. S. vulgaris vAU combined 10× genomics linked-reads, low-coverage Nanopore sequencing, and PacBio Iso-Seq full-length transcript scaffolding to generate a 1050 Mb assembly on 6222 scaffolds (7.6 Mb scaffold N50, 94.6% busco completeness). Further scaffolding against the high-quality zebra finch (Taeniopygia guttata) genome assigned 98.6% of the assembly to 32 putative nuclear chromosome scaffolds. Species-specific transcript mapping and gene annotation revealed good gene-level assembly and high functional completeness. Using S. vulgaris vAU, we demonstrate how the multifunctional use of PacBio Iso-Seq transcript data and complementary homology-based annotation of sequential assembly steps (assessed using a new tool, saaga) can be used to assess, inform, and validate assembly workflow decisions. We also highlight some counterintuitive behaviour in traditional busco metrics, and present buscomp, a complementary tool for assembly comparison designed to be robust to differences in assembly size and base-calling quality. This work expands our knowledge of avian genomes and the available toolkit for assessing and improving genome quality. The new genomic resources presented will facilitate further global genomic and transcriptomic analysis on this ecologically important species.

Published
2022

5. The RNA Atlas expands the catalog of human non-coding RNAs

Author

Lorenzi, L, Chiu, HS, Avila Cobos, F, Gross, S, Volders, PJ, Cannoodt, R, Nuytens, J, Vanderheyden, K, Anckaert, J, Lefever, S, Tay, AP, de Bony, EJ, Trypsteen, W, Gysens, F, Vromman, M, Goovaerts, T, Hansen, TB, Kuersten, S, Nijs, N, Taghon, T, Vermaelen, K, Bracke, KR, Saeys, Y, De Meyer, T, Deshpande, NP ; https://orcid.org/0000-0002-0324-8728, Anande, G, Chen, TW, Wilkins, MR ; https://orcid.org/0000-0002-5700-5684, Unnikrishnan, A ; https://orcid.org/0000-0001-5168-8755, De Preter, K, Kjems, J, Koster, J, Schroth, GP, Vandesompele, J, Sumazin, P, Mestdagh, P, Lorenzi, L, Chiu, HS, Avila Cobos, F, Gross, S, Volders, PJ, Cannoodt, R, Nuytens, J, Vanderheyden, K, Anckaert, J, Lefever, S, Tay, AP, de Bony, EJ, Trypsteen, W, Gysens, F, Vromman, M, Goovaerts, T, Hansen, TB, Kuersten, S, Nijs, N, Taghon, T, Vermaelen, K, Bracke, KR, Saeys, Y, De Meyer, T, Deshpande, NP ; https://orcid.org/0000-0002-0324-8728, Anande, G, Chen, TW, Wilkins, MR ; https://orcid.org/0000-0002-5700-5684, Unnikrishnan, A ; https://orcid.org/0000-0001-5168-8755, De Preter, K, Kjems, J, Koster, J, Schroth, GP, Vandesompele, J, Sumazin, P, and Mestdagh, P

Abstract

Existing compendia of non-coding RNA (ncRNA) are incomplete, in part because they are derived almost exclusively from small and polyadenylated RNAs. Here we present a more comprehensive atlas of the human transcriptome, which includes small and polyA RNA as well as total RNA from 300 human tissues and cell lines. We report thousands of previously uncharacterized RNAs, increasing the number of documented ncRNAs by approximately 8%. To infer functional regulation by known and newly characterized ncRNAs, we exploited pre-mRNA abundance estimates from total RNA sequencing, revealing 316 microRNAs and 3,310 long non-coding RNAs with multiple lines of evidence for roles in regulating protein-coding genes and pathways. Our study both refines and expands the current catalog of human ncRNAs and their regulatory interactions. All data, analyses and results are available for download and interrogation in the R2 web portal, serving as a basis for future exploration of RNA biology and function.

Published
2021

10. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author

Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcus, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Maris, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pirastu, Nicola, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, McArdle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Toomas, Keis, Aime, Tammesoo, Mari-Liis, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Anders, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, James, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thomas, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Gasparini, Paolo, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andres, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willems, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van Duijn, Cornelia M. McEniery CM, Wilkinson IB, Cockcroft JR, O'Shaughnessy KM, Newhouse SJ, Yasmin, Smith AV, Eiriksdottir G, Launer LJ, Sigurdsson S, Aspelund T, Gudnason V, De Bacquer D, Rietzschel ER, De Backer GG, Van Bortel L, De Buyzere ML, Segers P, Bekaert S, Gillebert TC, De Meyer T, Ferrucci L, Tanaka T, Johnson AD, Levy D, Benjamin EJ, Mitchell GF, Vita JA, Larson MG, Hamburg NM, Vasan RS, Isaacs A, Schut AF, Oostra BA, van Duijn CM, van Rijn MJ, Sie MP, Newman AB, Herrington DM, Andrews JS, Ding J, Sutton-Tyrrell KC, Harris TB, Howard TD, Liu Y, Parsa A, Shuldiner AR, McArdle PF, Gibson Q, Post WS, Dehghan A, Hofman A, Uitterlinden AG, Sijbrands EJ, Rivadeneira F, Mattace-Raso FU, Verwoert GC, Witteman JC, Scuteri A, Lakatta EG, Jewell E, Abecasis GR, Tarasov KV, Uda M, Najjar SS, Sanna S, Attwood T, Belz S, Braund P, Cambien F, Cooper J, Crisp-Hihn A, Deloukas P, Foad N, Eardman J, Goodall AH, Gracey J, Gray E, Gulde S, Gwilliams R, Heimerl S, Hengstenberg C, Jolley J, Krishnan U, Linsel-Nitschke P, Lloyd-Jones H, Lugauer I, Lundmark P, Maouche S, Moore JS, Muir D, Murray E, Nelson CP, Neudert J, Niblett D, O'Leary K, Ouwehand WH, Pollard H, Rankin A, Rice CM, Sager H, Samani NJ, Sambrook J, Schmitz G, Scholz M, Schroeder L, Schunkert H, Syvannen AC, Wallace C, Kathiresan S, Reilly MP, Erdmann J, Assimes TL, Boerwinkle E, Hall A, König IR, Laaksonen R, McPherson R, Thompson JR, Thorsteinsdottir U, Ziegler A, Absher D, Chen L, Cupples LA, Halperin E, Li M, Musunuru K, Preuss M, Schillert A, Thorleifsson G, Voight BF, Wells GA, Assime TL, Holm H, Roberts R, Stewart AF, Fortmann S, Go A, Hlatky M, Iribarren C, Knowles J, Myers R, Quertermous T, Sidney S, Risch N, Tang H, Blankenberg S, Zeller T, Wild P, Schnabel R, Sinning C, Lackner K, Tiret L, Nicaud V, Bickel C, Rupprecht HJ, Perret C, Proust C, Münzel T, Barbalic M, Bis J, Chen IY, Cupples L, Demissie-Banjaw S, Folsom A, Glazer N, Harris T, Heckbert S, Lumley T, Marciante K, Morrison A, O' Donnell CJ, Psaty BM, Rice K, Rotter JI, Siscovick DS, Smith N, Smith A, Taylor KD, van Duijn C, Volcik K, Whitteman J, Ramachandran V, Uitterlinden A, Gretarsdottir S, Gulcher JR, Kong A, Stefansson K, Thorgeirsson G, Andersen K, Fischer M, Grosshennig A, Lieb W, Stark K, Schreiber S, Wichmann HE, Aherrahrou Z, Bruse P, Doering A, Illig T, Klopp N, Loley C, Medack A, Meisinger C, Meitinger T, Nahrstedt J, Peters A, Wagner AK, Willenborg C, Böhm BO, Dobnig H, Grammer TB, Hoffmann MM, Kleber M, März W, Meinitzer A, Winkelmann BR, Pilz S, Renner W, Scharnagl H, Stojakovic T, Tomaschitz A, Winkler K, Guiducci C, Burtt N, Gabriel SB, O'Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, Dandona S, Jarinova O, Qu L, Wilensky R, Matthai W, Hakonarson HH, Devaney J, Burnett MS, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Knouff CW, Waterworth DM, Walker MC, Mooser V, Epstein SE, Rader DJ, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall AS, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Yang YA, Stricker BH, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Willerson JT, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Gao X, Yang Q, O'Connell JR, Schmidt H, Ketkar S, Hwang SJ, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria F, Metter J, de Boer IH, Siscovick D, Zillikens MC, Feitosa M, Province M, de Andrade M, Turner ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Coresh J, Schmidt R, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Felix SB, Watzinger N, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Reffelmann T, Redfield MM, Werdan K, Arnett DK, Blettner M, Friedrich N, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic N, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Vollenweider P, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Lightstone L, Scott J, Navis G, Elliott P, Kooner JS., Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), University of Leicester, Department of Genetics [Leicester], Erasmus University Rotterdam, Netherlands Genomics Initiative, Department of Epidemiology and Biostatistics, School of Public Health, Zahedan University of Medical Sciences, Washington University in Saint Louis (WUSTL), Queen Mary University of London (QMUL), National Heart, Lung and Blood Institute, Partenaires INRAE, Centre Hospitalier Universitaire Vaudois (CHUV), Université de Lausanne = University of Lausanne (UNIL), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Leiden University Medical Center (LUMC), Universiteit Leiden, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Department of Epidemiology, The Netherlands Cancer Institute, Department of Mathematics, Boston University [Boston] (BU), GlaxoSmithKline, Division of Community Health Sciences, St. George's, University of South Florida [Tampa] (USF), Universität Greifswald - University of Greifswald, University of Washington [Seattle], University of Tartu, Institute of Molecular and Cell Biology, Medical Research Council, Institut de Génomique, Centre National de Génotypage, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University Medical Center Groningen, Department of Genetics, University Medical Center Groningen [Groningen] (UMCG), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Massachusetts General Hospital [Boston], Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Università degli studi di Trieste = University of Trieste, Universität zu Lübeck = University of Lübeck [Lübeck], Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, The University of Western Australia (UWA), Department of Twin Research and Genetic Epidemiology, King's College London, London, University of Oxford, Medical University Graz, National Institute on Aging, Centre for population Health Sciences, University of Edinburgh, Uppsala University, Vrije Universiteit Amsterdam [Amsterdam] (VU), Western General Hospital, Harvard Medical School [Boston] (HMS), Brigham and Women's Hospital [Boston], University of Michigan System, University of Groningen, Ealing Hospital, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Medical Genetics Institute, Cedars-Sinai Medical Center, University of Tampere, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Split, The University of Texas Health Science Center at Houston (UTHealth), Johns Hopkins University (JHU), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Swiss Institute of Bioinformatics [Lausanne] (SIB), Finnish Institute of Occupational Health, National Institute of Health and Welfare, University of Oulu, Lapland Central Hospital, University of Bristol [Bristol], Institute for Community Medicine, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), US National Institutes of Health, National Heart, Lung, and Blood Institute, European, Epidemiology, Internal Medicine, Public Health, Clinical Genetics, Université de Lausanne (UNIL), LeidenUniversity Medical Centre, University of Iceland, Università degli studi di Trieste, Universität zu Lübeck [Lübeck], University of Western Australia, University of Oxford [Oxford], VU University Amsterdam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Human genetics, Psychiatry, EMGO - Mental health, NCA - Anxiety & Depression, Epidemiology and Data Science, Medical Research Council (MRC), Louise V., Wain, Germaine C., Verwoert, Paul F., O'Reilly, Gang, Shi, Toby, Johnson, Andrew D., Johnson, Murielle, Bochud, Kenneth M., Rice, Peter, Henneman, Albert V., Smith, Georg B., Ehret, Najaf, Amin, Martin G., Larson, Vincent, Mooser, David, Hadley, Marcus, Dörr, Joshua C., Bi, Thor, Aspelund, Tõnu, Esko, A. Cecile J. W., Janssen, Jing Hua, Zhao, Simon, Heath, Maris, Laan, Jingyuan, Fu, Giorgio, Pisti, Jian'An, Luan, Pankaj, Arora, Gavin, Luca, Pirastu, Nicola, Irene, Pichler, Anne U., Jackson, Rebecca J., Webster, Feng, Zhang, John F., Peden, Helena, Schmidt, Toshiko, Tanaka, Harry, Campbell, Wilmar, Igl, Yuri, Milaneschi, Jouke Jan, Hottenga, Veronique, Vitart, Daniel I., Chasman, Stella, Trompet, Jennifer L., Bragg Gresham, Behrooz Z., Alizadeh, John C., Chamber, Xiuqing, Guo, Terho, Lehtimäki, Brigitte, Kühnel, Lorna M., Lopez, Ozren, Polašek, Mladen, Boban, Christopher P., Nelson, Alanna C., Morrison, Vasyl, Pihur, Santhi K., Ganesh, Albert, Hofman, Suman, Kundu, Francesco U. S., Mattace Raso, Fernando, Rivadeneira, Eric J. G., Sijbrand, Andre G., Uitterlinden, Shih Jen, Hwang, Ramachandran S., Vasan, Thomas J., Wang, Sven, Bergmann, Peter, Vollenweider, Gérard, Waeber, Jaana, Laitinen, Anneli, Pouta, Paavo, Zitting, Wendy L., Mcardle, Heyo K., Kroemer, Uwe, Völker, Henry, Völzke, Nicole L., Glazer, Kent D., Taylor, Tamara B., Harri, Helene, Alavere, Toomas, Haller, Aime, Kei, Mari Liis, Tammesoo, Yurii, Aulchenko, Inês, Barroso, Kay Tee, Khaw, Pilar, Galan, Serge, Hercberg, Mark, Lathrop, Susana, Eyheramendy, Elin, Org, Siim, Sõber, Xiaowen, Lu, Ilja M., Nolte, Brenda W., Penninx, Tanguy, Corre, Corrado, Masciullo, Cinzia, Sala, Leif, Groop, Benjamin F., Voight, Olle, Melander, Christopher J., O'Donnell, Veikko, Salomaa, D'Adamo, ADAMO PIO, Antonella, Fabretto, Flavio, Faletra, Sheila, Ulivi, Fabiola Del Greco, M, Maurizio, Facheri, Francis S., Collin, Richard N., Bergman, John P., Beilby, Joseph, Hung, A., William Musk, Massimo, Mangino, So Youn, Shin, Nicole, Soranzo, Hugh, Watkin, Anuj, Goel, Anders, Hamsten, Pierre, Gider, Marisa, Loitfelder, Marion, Zeginigg, Dena, Hernandez, Samer S., Najjar, Pau, Navarro, Sarah H., Wild, Anna Maria, Corsi, Andrew, Singleton, Eco J. C., de Geu, Gonneke, Willemsen, Alex N., Parker, Lynda M., Rose, Brendan, Buckley, David, Stott, Marco, Orru, Manuela, Uda, Melanie M., van der Klauw, Weihua, Zhang, Xinzhong, Li, James, Scott, Yii Der Ida, Chen, Gregory L., Burke, Mika, Kähönen, Jorma, Viikari, Angela, Döring, Thomas, Meitinger, Gail, Davie, John M., Starr, Valur, Emilsson, Andrew, Plump, Jan H., Lindeman, Peter A. C., 't Hoen, Inke R., König, Janine F., Felix, Robert, Clarke, Jemma C., Hopewell, Halit, Ongen, Monique, Breteler, Stéphanie, Debette, Anita L., Destefano, Myriam, Fornage, Gary F., Mitchell, Nicholas L., Smith, Hilma, Holm, Kari, Stefansson, Gudmar, Thorleifsson, Unnur, Thorsteinsdottir, Nilesh J., Samani, Michael, Preu, Igor, Rudan, Caroline, Hayward, Ian J., Deary, H., Erich Wichmann, Olli T., Raitakari, Walter, Palma, Jaspal S., Kooner, Ronald P., Stolk, J., Wouter Jukema, Alan F., Wright, Dorret I., Boomsma, Stefania, Bandinelli, Ulf B., Gyllensten, James F., Wilson, Luigi, Ferrucci, Reinhold, Schmidt, Martin, Farrall, Tim D., Spector, Lyle J., Palmer, Jaakko, Tuomilehto, Arne, Pfeufer, Gasparini, Paolo, David, Siscovick, David, Altshuler, Ruth J. F., Loo, Daniela, Toniolo, Harold, Snieder, Christian, Gieger, Pierre, Meneton, Nicholas J., Wareham, Ben A., Oostra, Andres, Metspalu, Lenore, Launer, Rainer, Rettig, David P., Strachan, Jacques S., Beckmann, Jacqueline C. M., Witteman, Jeanette, Erdmann, Ko Willems van, Dijk, Eric, Boerwinkle, Michael, Boehnke, Paul M., Ridker, Marjo Riitta, Jarvelin, Aravinda, Chakravarti, Goncalo R., Abecasi, Vilmundur, Gudnason, Christopher Newton, Cheh, Daniel, Levy, Patricia B., Munroe, Bruce M., Psaty, Mark J., Caulfield, Dabeeru C., Rao, Martin D., Tobin, Paul, Elliott, Cornelia M., van Duijn, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcu, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. 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T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andre, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willem, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van, Duijn, Cornelia M., McEniery CM, Wilkinson, Ib, Cockcroft, Jr, O'Shaughnessy, Km, Newhouse, Sj, Yasmin, Smith, Av, Eiriksdottir, G, Launer, Lj, Sigurdsson, S, Aspelund, T, Gudnason, V, De Bacquer, D, Rietzschel, Er, De Backer, Gg, Van Bortel, L, De Buyzere, Ml, Segers, P, Bekaert, S, Gillebert, Tc, De Meyer, T, Ferrucci, L, Tanaka, T, Johnson, Ad, Levy, D, Benjamin, Ej, Mitchell, Gf, Vita, Ja, Larson, Mg, Hamburg, Nm, Vasan, R, Isaacs, A, Schut, Af, Oostra, Ba, van Duijn, Cm, van Rijn, Mj, Sie, Mp, Newman, Ab, Herrington, Dm, Andrews, J, Ding, J, Sutton-Tyrrell, Kc, Harris, Tb, Howard, Td, Liu, Y, Parsa, A, Shuldiner, Ar, Mcardle, Pf, Gibson, Q, Post, 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Thorleifsson, G, Voight, Bf, Wells, Ga, Assime, Tl, Holm, H, Roberts, R, Stewart, Af, Fortmann, S, Go, A, Hlatky, M, Iribarren, C, Knowles, J, Myers, R, Quertermous, T, Sidney, S, Risch, N, Tang, H, Blankenberg, S, Zeller, T, Wild, P, Schnabel, R, Sinning, C, Lackner, K, Tiret, L, Nicaud, V, Bickel, C, Rupprecht, Hj, Perret, C, Proust, C, Münzel, T, Barbalic, M, Bis, J, Chen, Iy, Cupples, L, Demissie-Banjaw, S, Folsom, A, Glazer, N, Harris, T, Heckbert, S, Lumley, T, Marciante, K, Morrison, A, O' Donnell, Cj, Psaty, Bm, Rice, K, Rotter, Ji, Siscovick, D, Smith, N, Smith, A, Taylor, Kd, van Duijn, C, Volcik, K, Whitteman, J, Ramachandran, V, Uitterlinden, A, Gretarsdottir, S, Gulcher, Jr, Kong, A, Stefansson, K, Thorgeirsson, G, Andersen, K, Fischer, M, Grosshennig, A, Lieb, W, Stark, K, Schreiber, S, Wichmann, He, Aherrahrou, Z, Bruse, P, Doering, A, Illig, T, Klopp, N, Loley, C, Medack, A, Meisinger, C, Meitinger, T, Nahrstedt, J, Peters, A, Wagner, Ak, Willenborg, C, Böhm, Bo, Dobnig, H, Grammer, Tb, Hoffmann, Mm, Kleber, M, März, W, Meinitzer, A, Winkelmann, Br, Pilz, S, Renner, W, Scharnagl, H, Stojakovic, T, Tomaschitz, A, Winkler, K, Guiducci, C, Burtt, N, Gabriel, Sb, O'Donnell, Cj, Elosua, R, Peltonen, L, Salomaa, V, Schwartz, Sm, Melander, O, Altshuler, D, Dandona, S, Jarinova, O, Qu, L, Wilensky, R, Matthai, W, Hakonarson, Hh, Devaney, J, Burnett, M, Pichard, Ad, Kent, Km, Satler, L, Lindsay, Jm, Waksman, R, Knouff, Cw, Waterworth, Dm, Walker, Mc, Mooser, V, Epstein, Se, Rader, Dj, Wright, Bj, Balmforth, Aj, Ball, Sg, Smith, Nl, Felix, Jf, Morrison, Ac, Demissie, S, Glazer, Nl, Loehr, Lr, Rosamond, Wd, Bis, Jc, Folsom, Ar, Benjamin, E, Aulchenko, Y, Haritunians, T, Couper, D, Murabito, J, Yang, Ya, Stricker, Bh, Gottdiener, J, Chang, Pp, Wang, Tj, Rice, Km, Heckbert, Sr, Fox, Er, Willerson, Jt, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Gao, X, Yang, Q, O'Connell, Jr, Schmidt, H, Ketkar, S, Hwang, Sj, Teumer, A, Paré, G, Atkinson, Ej, Lohman, K, Cornelis, Mc, Probst-Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Rampersaud, E, Mitchell, Bd, Arking, De, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, F, Metter, J, de Boer, Ih, Zillikens, Mc, Feitosa, M, Province, M, de Andrade, M, Turner, St, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, A, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Prokopenko, I, Wang, W, Coresh, J, Schmidt, R, Shlipak, Mg, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Felix, Sb, Watzinger, N, Homuth, G, Aragam, J, Dörr, M, Zweiker, R, Lind, L, Rodeheffer, Rj, Greiser, Kh, Deckers, Jw, Stritzke, J, Lackner, Kj, Ingelsson, E, Kullo, I, Haerting, J, Reffelmann, T, Redfield, Mm, Werdan, K, Arnett, Dk, Blettner, M, Friedrich, N, Chambers, Jc, Zhang, W, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Davey Smith, G, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, N, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, Homan van der Heide, Jj, Hepkema, Bg, Hernandez-Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Munroe, Pb, Nordfors, L, Penninx, Bw, Perucha, E, Pouta, A, Roderick, Pj, Ruokonen, A, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Vollenweider, P, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Lightstone, L, Scott, J, Navis, G, Elliott, P, and Kooner, Js.

Subjects
Netherlands Twin Register (NTR), Linkage disequilibrium, pulse pressure, mean arterial pressure, genome-wide, [SDV]Life Sciences [q-bio], Genome-wide association study, BLOOD-PRESSURE, Blood Pressure, 030204 cardiovascular system & hematology, Linkage Disequilibrium, 0302 clinical medicine, RELEVANCE, CardioGram, Medicine and Health Sciences, Genetics & Heredity, ddc:616, Genetics, 0303 health sciences, Genome-wide association, 11 Medical And Health Sciences, Arteries, ADRENERGIC-RECEPTOR TRAFFICKING, Pulse pressure, EchoGen consortium, Hypertension, HEART-FAILURE, arterial pressure, Case-Control Studie, Life Sciences & Biomedicine, Human, circulatory and respiratory physiology, medicine.medical_specialty, Mean arterial pressure, Arterie, AortaGen Consortium, Cardiogenics consortium, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Article, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Humans, cardiovascular diseases, METAANALYSIS, 030304 developmental biology, Genetic association, Science & Technology, HYPERTENSION, MORTALITY, Case-control study, CARDIOVASCULAR-DISEASE RISK, 06 Biological Sciences, GENE, MICE, Endocrinology, Blood pressure, CKDGen consortium, Genetic Loci, Case-Control Studies, KidneyGen consortium, CHARGE Consortium Heart Failure Working Group, LifeLines Cohort Study, Developmental Biology, Follow-Up Studies, Genome-Wide Association Study
Abstract

Les affiliations des 100 premiers auteurs sont renseignées dans la notice. Les affiliations des autres auteurs sont disponibles à la fin de la publication.; International audience; Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Published
2016
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11. Identification of Intermediates in Zeolite‐Catalyzed Reactions by In Situ UV/Vis Microspectroscopy and a Complementary Set of Molecular Simulations

Author

Hemelsoet, K.L.J., Qian, Q., De Meyer, T., De Wispelaere, K., De Sterck, B., Weckhuysen, B.M., Waroquier, M., Van Speybroeck, V., Inorganic Chemistry and Catalysis, Sub Inorganic Chemistry and Catalysis, Sub Inorganic Chemistry and Catalysis, and Faculteit Betawetenschappen

Subjects
Heterogeneous catalysis, Absorption spectroscopy, Vis spectroscopy, 010405 organic chemistry, Chemistry, Nanoporous, Organic Chemistry, Supramolecular chemistry, General Chemistry, Time-dependent density functional theory, Molecular dynamics, 010402 general chemistry, Photochemistry, 01 natural sciences, Catalysis, Uv, 0104 chemical sciences, Density functional calculations, Ultraviolet visible spectroscopy, Zeolites, Density functional theory, Absorption (chemistry)
Abstract

The optical absorption properties of (poly)aromatic hydrocarbons occluded in a nanoporous environment were investigated by theoretical and experimental methods. The carbonaceous species are an essential part of a working catalyst for the methanol-toolefins (MTO) process. In situ UV/Vis microscopy measurements on methanol conversion over the acidic solid catalysts H-SAPO-34 and H-SSZ-13 revealed the growth of various broad absorption bands around 400, 480, and 580 nm. The cationic nature of the involved species was determined by interaction of ammonia with the methanol- treated samples. To determine which organic species contribute to the various bands, a systematic series of aromatics was analyzed by means of time-dependent density functional theory (TDDFT) calculations. Static gas-phase simulations revealed the influence of structurally different hydrocarbons on the absorption spectra, whereas the influence of the zeolitic framework was examined by using supramolecular models within a quantum mechanics/molecular mechanics framework. To fully understand the origin of the main absorption peaks, a molecular dynamics (MD) study on the organic species trapped in the inorganic host was essential. During such simulation the flexibility is fully taken into account and the effect on the UV/ Vis spectra is determined by performing TDDFT calculations on various snapshots of the MD run. This procedure allows an energy absorption scale to be provided and the various absorption bands determined from in situ UV/Vis spectra to be assigned to structurally different species.

Published
2013
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12. Gender and telomere length:Systematic review and meta-analysis

Author

Gardner M, Bann D, Wiley L, Cooper R, Hardy R, Nitsch D, Martin Ruiz C, Shiels P, Sayer AA, BARBIERI, Michelangela, Bekaert S, Bischoff C, Brooks Wilson A, Chen W, Cooper C, Christensen K, De Meyer T, Deary I, Der G, Roux AD, Fitzpatrick A, Hajat A, Halaschek Wiener J, Harris S, Hunt SC, Jagger C, Jeon HS, Kaplan R, Kimura M, Lansdorp P, Li C, Maeda T, Mangino M, Nawrot TS, Nilsson P, Nordfjall K, Ren F, Riabowol K, Robertson T, Roos G, Staessen JA, Spector T, Tang N, Unryn B, van der Harst P, Woo J, Xing C, Yadegarfar ME, Park JY, Young N, Kuh D, vonZglinicki T, Ben Shlomo Y, the Halcyon study team, PAOLISSO, Giuseppe, Gardner, M, Bann, D, Wiley, L, Cooper, R, Hardy, R, Nitsch, D, Martin Ruiz, C, Shiels, P, Sayer, Aa, Barbieri, Michelangela, Bekaert, S, Bischoff, C, Brooks Wilson, A, Chen, W, Cooper, C, Christensen, K, De Meyer, T, Deary, I, Der, G, Roux, Ad, Fitzpatrick, A, Hajat, A, Halaschek Wiener, J, Harris, S, Hunt, Sc, Jagger, C, Jeon, H, Kaplan, R, Kimura, M, Lansdorp, P, Li, C, Maeda, T, Mangino, M, Nawrot, T, Nilsson, P, Nordfjall, K, Paolisso, Giuseppe, Ren, F, Riabowol, K, Robertson, T, Roos, G, Staessen, Ja, Spector, T, Tang, N, Unryn, B, van der Harst, P, Woo, J, Xing, C, Yadegarfar, Me, Park, Jy, Young, N, Kuh, D, Vonzglinicki, T, Ben Shlomo, Y, and the Halcyon study, Team

Published
2014

13. The role of methylation in metastasis of oral squamous cell carcinoma: Understanding the OSCC methylome

Author

Clausen, M., Melchers, L.J., De Meyer, T., Denil, S., Criekinge, W., Wisman, G.B., Roodenburg, J.L.N., Schuuring, E., Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
diagnosis, survival, primary tumor, promoter region, data base, chromosome 7, metastasis, human, hospital, gene, genome, mouth squamous cell carcinoma, metastasis potential, marker, therapy, DNA methylation, epigenetics, lymph node metastasis, messenger RNA, imaging, DNA, lymph node, biological marker, stomatognathic diseases, quality of life, palpation, methylation, patient, neoplasm
Abstract

Background: Oral Squamous Cell Carcinoma (OSCC) is characterized by an increasing incidence and a 60% 5-year survival. The most important prognostic factor for OSCC is the presence of lymph node (LN) metastases but the detection of LN metastases in the clinic by palpation and imaging is inaccurate resulting in under and overtreatment of patients. To improve LN diagnosis new detection methods are needed. DNA methylation studies can be used to identify novel biomarkers, as epigenetics have been established as an important regulator of metastatic potential. The aim of this study is to identify new DNA methylation markers that predict LN metastasis in OSCC. Materials and Methods: Genome-wide methylation patterns of metastatic (n = 6) and non-metastatic OSCC (n = 6) were assessed using MethylCap- Seq. Subsequently, analysis was performed on the most differentially methylated loci to identify pathways and genomic loci associated with LN metastasis. Additionally, the methylation data were combined with expression data of 222 OSCC patients acquired by an expression microarray with a 696 gene panel associated with N-status in OSCC. Finally, we validated these findings on the OSCC samples (n = 174) in The Cancer Genome Atlas (TCGA). Results: We found that genes on chromosome 7 are the most hypermethylated in metastatic OSCC in comparison to non-metastatic OSCC, more specifically a four million bp loci around the EGFR gene. In total 26 genes were found to be differentially methylated by MethylCap- Seq as well as differentially expressed by microarray. In the OSCC TCGA validation cohort, all 26 genes are significantly differentially expressed between metastatic and non-metastatic OSCC. For these 26 differentially expressed genes 88 probes were found in the TCGA Infinium 450k methylation data that are both significantly differentially methylated between the two groups and correlated with mRNA levels. Finally, six of these probes overlapped with the genomic regions annotated by MethylCap-Seq, representing five genes. Conclusion: We identified chromosomal loci, pathways and gene promoters associated with LN metastasis in OSCC patients. For 10 genes the differential methylation, expression and correlation between methylation and expression was validated on an independent OSCC cohort from the TCGA database. Increased understanding of the metastatic OSCC methylome will contribute to the identification of DNA methylation markers, pathways and potential therapeutic targets in OSCC primary tumors that will improve chances of providing the proper lymph node treatment and may result in improvement of survival and quality of life.

Published
2014

14. Reproducibility of telomere length assessment: an international collaborative study

Author

Cooper, Rachel, Martin-Ruiz, CM, Baird, D, Roger, L, Boukamp, P, Krunic, D, Cawthon, R, Dokter, MM, van, der Harst P, Bekaert, S, de, Meyer T, Roos, G, Svenson, U, Codd, V, Samani, NJ, McGlynn, L, Shiels, PG, Pooley, KA, Dunning, AM, Cooper, R, Wong, A, Kingston, A, and von, Zglinicki T

Abstract

Background: Telomere length is a putative biomarker of ageing, morbidity and mortality. Its application is hampered by lack of widely applicable reference ranges and uncertainty regarding the present limits of measurement reproducibility within and between laboratories. Methods: We instigated an international collaborative study of telomere length assessment: 10 different laboratories, employing 3 different techniques [Southern blotting, single telomere length analysis (STELA) and real-time quantitative PCR (qPCR)] performed two rounds of fully blinded measurements on 10 human DNA samples per round to enable unbiased assessment of intra- and inter-batch variation between laboratories and techniques. Results: Absolute results from different laboratories differed widely and could thus not be compared directly, but rankings of relative telomere lengths were highly correlated (correlation coefficients of 0.63–0.99). Intra-technique correlations were similar for Southern blotting and qPCR and were stronger than inter-technique ones. However, inter-laboratory coefficients of variation (CVs) averaged about 10% for Southern blotting and STELA and more than 20% for qPCR. This difference was compensated for by a higher dynamic range for the qPCR method as shown by equal variance after z-scoring. Technical variation per laboratory, measured as median of intra- and inter-batch CVs, ranged from 1.4% to 9.5%, with differences between laboratories only marginally significant ( P = 0.06). Gel-based and PCR-based techniques were not different in accuracy. Conclusions: Intra- and inter-laboratory technical variation severely limits the usefulness of data pooling and excludes sharing of reference ranges between laboratories. We propose to establish a common set of physical telomere length standards to improve comparability of telomere length estimates between laboratories.

Published
2014

15. Microbial Community Dynamics and Response to Plant Growth-Promoting Microorganisms in the Rhizosphere of Four Common Food Crops Cultivated in Hydroponics

Author

Sheridan, C., primary, Depuydt, P, additional, De Ro, M., additional, Petit, C., additional, Van Gysegem, E., additional, Delaere, P., additional, Dixon, M., additional, Stasiak, M., additional, Aciksöz, S. B., additional, Frossard, E., additional, Paradiso, R., additional, De Pascale, S., additional, Ventorino, V., additional, De Meyer, T., additional, Sas, B., additional, and Geelen, D., additional

Published
2016
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16. RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis

Author

Clausen, M. J. A. M., primary, Melchers, L. J., additional, Mastik, M. F., additional, Slagter-Menkema, L., additional, Groen, H. J. M., additional, Laan, B. F. A. M. van der, additional, van Criekinge, W., additional, de Meyer, T., additional, Denil, S., additional, van der Vegt, B., additional, Wisman, G. B. A., additional, Roodenburg, J. L. N., additional, and Schuuring, E., additional

Published
2016
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19. 779 Effect of sunitinib therapy on intratumoural heterogeneity and differential expression of genetic mutations and DNA methylation in metastatic renal cell cancer

Author

Stewart, G., primary, Van Neste, C., additional, Meynert, A., additional, Semple, C., additional, O'Mahony, F., additional, Laird, A., additional, Mackay, A., additional, Trooskens, G., additional, Van Criekinge, W., additional, De Meyer, T., additional, Powles, T., additional, and Harrison, D., additional

Published
2015
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21. Studying telomeres in a longitudinal population based study

Author

E. Rietzschel, De Buyzere Ml, Sofie Bekaert, De Meyer T, and Van Criekinge W

Subjects
Genetics, Male, Aging, Chromosome Mapping, Mitosis, Age dependent, Disease, Biology, Telomere, Models, Biological, Chromosomes, Population based study, Oxidative Stress, Genetics, Population, Phenotype, Cardiovascular Diseases, Population study, Biomarker (medicine), Humans, Female, Biomarkers, Cellular Senescence
Abstract

Telomeres, the termini of linear chromosomes, consist of large but variable numbers of DNA oligomer repeats embedded in a nucleoprotein complex. In humans, telomere length (TL) is largely genetically determined but also featured by an age dependent attrition. TL has therefore been put forward as a marker for biological aging and was also reported to be associated with aging diseases such as cardiovascular disease. However it remains unclear whether the biomarker value in a particular disease depends on shorter TL at birth or rather if it's a mere reflection of an accelerated telomere attrition during lifetime, or else, if it is a combination of both. While the importance of telomere attrition is supported by cross-sectional evidence associating shorter telomeres with oxidative stress and inflammation, longitudinal studies are required to accurately assess telomere attrition and its presumed link with accelerated aging. In this review we present different models for the biomarker value of TL and discuss the theoretical and methodological considerations of studying TL in a longitudinal population study with a special emphasis on cardiovascular disease.

Published
2007

22. Next-generation technologies and data analytical approaches for epigenomics

Author

Mensaert, Klaas, Denil, Simon, Trooskens, Geert, Van Criekinge, Wim, Thas, Olivier, De Meyer, T, Mensaert, Klaas, Denil, Simon, Trooskens, Geert, Van Criekinge, Wim, Thas, Olivier, and De Meyer, T

Abstract

Epigenetics refers to the collection of heritable features that modulate the genome-environment interaction without being encoded in the actual DNA sequence. While being mitotically and sometimes even meiotically transmitted, epigenetic traits often demonstrate extensive flexibility. This allows cells to acquire diverse gene expression patterns during differentiation, but also to adapt to a changing environment. However, epigenetic alterations are not always beneficial to the organism, as they are, for example, frequently identified in human diseases such as cancer. Accurate and cost-efficient genome-scale profiling of epigenetic features is thus of major importance to pinpoint these "epimutations," for example, to monitor the epigenetic impact of environmental exposure. Over the last decade, the field of epigenetics has been revolutionized by several innovative "epigenomics" technologies exactly addressing this need. In this review, we discuss and compare widely used next-generation methods to assess DNA methylation and hydroxymethylation, noncoding RNA expression, histone modifications, and nucleosome positioning. Although recent methods are typically based on "second-generation" sequencing, we also pay attention to still commonly used array- and PCR-based methods, and look forward to the additional advantages of single-molecule sequencing. As the current bottleneck in epigenomics research is the analysis rather than generation of data, the basic difficulties and problem-solving strategies regarding data preprocessing and statistical analysis are introduced for the different technologies. Finally, we also consider the complications associated with epigenomic studies of species with yet unsequenced genomes and possible solutions. 2013 Wiley Periodicals, Inc.

Published
2014

24. Identification of Intermediates in Zeolite-Catalyzed Reactions Using In-situ UV/Vis Micro- Spectroscopy and a Complementary Set of Molecular Simulations

Author

Inorganic Chemistry and Catalysis, Sub Inorganic Chemistry and Catalysis, Hemelsoet, K.L.J., Qian, Q., De Meyer, T., De Wispelaere, K., De Sterck, B., Weckhuysen, B.M., Waroquier, M., Van Speybroeck, V., Inorganic Chemistry and Catalysis, Sub Inorganic Chemistry and Catalysis, Hemelsoet, K.L.J., Qian, Q., De Meyer, T., De Wispelaere, K., De Sterck, B., Weckhuysen, B.M., Waroquier, M., and Van Speybroeck, V.

Published
2013

32. Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer

Author

Stewart, GD, Powles, T, Van Neste, C, Meynert, A, O'Mahony, F, Laird, A, Deforce, D, Van Nieuwerburgh, F, Trooskens, G, Van Criekinge, W, De Meyer, T, and Harrison, DJ

Subjects
VHL, renal cancer, methylation, heterogeneity, urologic and male genital diseases, mutations, 3. Good health
Abstract

Background: Genetic intratumoral heterogeneity (ITH) hinders biomarker development in metastatic clear cell renal cancer (mccRCC). Epigenetic relative to genetic ITH or the presence of consistent epigenetic changes following targeted therapy in mccRCC have not been evaluated. The aim of this study was to determine methylome/genetic ITH and to evaluate specific epigenetic and genetic changes associated with sunitinib therapy. Patients and methods: Multi-region DNA sampling performed on sequential frozen pairs of primary tumor tissue from 14 metastatic ccRCC patients, in the Upfront Sunitinib (SU011248) Therapy Followed by Surgery in Patients with Metastatic Renal Cancer: a Pilot Phase II Study (SuMR; ClinicalTrials.gov identifier: NCT01024205), at presentation (biopsy) and after 3-cycles of 50mg sunitinib (nephrectomy). Untreated biopsy and nephrectomy samples before and after renal artery ligation were controls. Ion Proton sequencing of 48 key ccRCC genes, and MethylCap-seq DNA methylation analysis was performed, data was analysed using the statistical computing environment R. Results: Unsupervised hierarchical clustering revealed complete methylome clustering of biopsy and three nephrectomy samples for each patient (14/14 patients). For mutational status, untreated biopsy and all treated nephrectomy samples clustered together in 8/13 (61.5%) patients. The only methylation target significantly altered following sunitinib therapy was VHL promoter region 7896829 which was hypermethylated with treatment (FDR=0.077, P

33. Identification of novel genetic loci associated with thyroid peroxidase antibodies and clinical thyroid disease

Author

Medici, M., Porcu, E., Pistis, G., Teumer, A., Brown, S. J., Jensen, R. A., Rawal, R., Roef, G. L., Plantinga, T. S., Vermeulen, S. H., Lahti, J., Simmonds, M. J., Husemoen, L. N. N., Freathy, R. M., Shields, B. M., Pietzner, D., Nagy, R., Broer, L., Chaker, L., Korevaar, T. I. M., Plia, M. G., Sala, C., Volker, U., Richards, J. B., Sweep, F. C., Gieger, C., Corre, T., Kajantie, E., Thuesen, B., Taes, Y. E., Visser, W. E., Hattersley, A. T., Kratzsch, J., Hamilton, A., Li, W., Homuth, G., Lobina, M., Mariotti, S., Soranzo, N., Cocca, M., Nauck, M., Spielhagen, C., Ross, A., Arnold, A., van de Bunt, M., Liyanarachchi, S., Heier, M., Grabe, H. J., Masciullo, C., Galesloot, T. E., Lim, E. M., Reischl, E., Leedman, P. J., Lai, S., Delitala, A., Bremner, A. P., Philips, D. I. W., Beilby, J. P., Mulas, A., Vocale, M., Abecasis, G., Forsen, T., James, A., Widen, E., Hui, J., Prokisch, H., Rietzschel, E. E., Palotie, A., Feddema, P., Fletcher, S. J., Schramm, K., Rotter, J. I., Kluttig, A., Radke, D., Traglia, M., Surdulescu, G. L., He, H., Franklyn, J. A., Tiller, D., Vaidya, B., de Meyer, T., Jørgensen, T., Eriksson, J. G., O’Leary, P. C., Wichmann, E., Hermus, A. R., Psaty, B. M., Ittermann, T., Hofman, A., Bosi, E., Schlessinger, D., Wallaschofski, H., Pirastu, N., Aulchenko, Y.S., de la Chapelle, A., Netea-Maier, R.T., Gough, S.C.L., Meyer zu Schwabedissen, H., Frayling, T.M., Kaufman, J.M., Linneberg, A., Raikkonen, K., Smit, J.W.A., Kiemeney, L.A., Rivadeneira, F., Uitterlinden, A.G., Walsh, J.P., Meisinger, C., den Heijer, M., Visser, T.J., Spector, T.D., Wilson, S.G., Volzke, H., Cappola, A., Toniolo, D., Sanna, S., Naitza, S., Peeters, R.P., Medici, M., Porcu, E., Pistis, G., Teumer, A., Brown, S. J., Jensen, R. A., Rawal, R., Roef, G. L., Plantinga, T. S., Vermeulen, S. H., Lahti, J., Simmonds, M. J., Husemoen, L. N. N., Freathy, R. M., Shields, B. M., Pietzner, D., Nagy, R., Broer, L., Chaker, L., Korevaar, T. I. M., Plia, M. G., Sala, C., Volker, U., Richards, J. B., Sweep, F. C., Gieger, C., Corre, T., Kajantie, E., Thuesen, B., Taes, Y. E., Visser, W. E., Hattersley, A. T., Kratzsch, J., Hamilton, A., Li, W., Homuth, G., Lobina, M., Mariotti, S., Soranzo, N., Cocca, M., Nauck, M., Spielhagen, C., Ross, A., Arnold, A., van de Bunt, M., Liyanarachchi, S., Heier, M., Grabe, H. J., Masciullo, C., Galesloot, T. E., Lim, E. M., Reischl, E., Leedman, P. J., Lai, S., Delitala, A., Bremner, A. P., Philips, D. I. W., Beilby, J. P., Mulas, A., Vocale, M., Abecasis, G., Forsen, T., James, A., Widen, E., Hui, J., Prokisch, H., Rietzschel, E. E., Palotie, A., Feddema, P., Fletcher, S. J., Schramm, K., Rotter, J. I., Kluttig, A., Radke, D., Traglia, M., Surdulescu, G. L., He, H., Franklyn, J. A., Tiller, D., Vaidya, B., de Meyer, T., Jørgensen, T., Eriksson, J. G., O’Leary, P. C., Wichmann, E., Hermus, A. R., Psaty, B. M., Ittermann, T., Hofman, A., Bosi, E., Schlessinger, D., Wallaschofski, H., Pirastu, N., Aulchenko, Y.S., de la Chapelle, A., Netea-Maier, R.T., Gough, S.C.L., Meyer zu Schwabedissen, H., Frayling, T.M., Kaufman, J.M., Linneberg, A., Raikkonen, K., Smit, J.W.A., Kiemeney, L.A., Rivadeneira, F., Uitterlinden, A.G., Walsh, J.P., Meisinger, C., den Heijer, M., Visser, T.J., Spector, T.D., Wilson, S.G., Volzke, H., Cappola, A., Toniolo, D., Sanna, S., Naitza, S., and Peeters, R.P.

Abstract

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10−8) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68–2.81, P = 8.1×10−8), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26–1.82, P = 2.9×10−6), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66–0.89, P = 6.5×10−4). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22–1.54, P = 1.2×10−7 and OR: 1.25, 95% CI 1.12–1.39, P = 6.2×10−5). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18–2.10, P = 1.9×10−3). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do

35. App based monitoring of heart rate via FibriCheck to facilitate teleconsultations: from COVID-19 to clinical practice?

Author

Michiel Delesie, L Knaepen, Johan Saenen, Lien Desteghe, Lars Grieten, Andrea Sarkozy, Johan Vijgen, Hein Heidbuchel, Hielko Miljoen, T. De Meyer, Dominik Linz, A. Wildiers, KNAEPEN, Lieselotte, DELESIE, Michiel, De, Meyer T., Wildiers, A., Sarkozy, A., Saenen, J., Miljoen, H., VIJGEN, Johan, GRIETEN, Lars, Linz, D., DESTEGHE, Lien, and HEIDBUCHEL, Hein

Subjects
AcademicSubjects/MED00605, Advanced and Specialized Nursing, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Remote Patient Monitoring and Telehealth, business.industry, Remote patient monitoring, AcademicSubjects/MED00600, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Cardiac arrhythmia, Clinical Practice, Medical–Surgical Nursing, Emergency medicine, Heart rate, Palpitations, Medicine, AcademicSubjects/MED00200, medicine.symptom, Cardiology and Cardiovascular Medicine, business, AcademicSubjects/MED00020
Abstract

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Part of this project was realized with financial support from the city of Antwerp in the context of the call "Innovative solutions for Corona” Background During the first peak of the COVID-19 pandemic, face-to-face cardiology visits had to be replaced by teleconsultations but lacking the standard performed electrocardiogram. Instead, app-based monitoring of patients’ heart rate and rhythm using photoplethysmography (PPG) technology was available as an alternative to aid these teleconsultations. Purpose Evaluation of the feasibility to initiate remotely PPG recordings with FibriCheck (Qompium, Hasselt, Belgium) and of the value of using FibriCheck before and after teleconsultation to substitute in-person arrhythmia consultations in three Belgian hospitals (Antwerp University Hospital, Heilig-Hart Hospital Lier and Jessa Hospital Hasselt). Methods Patients known with AF or with suspected arrhythmia symptoms during teleconsultation were contacted for the activation of FibriCheck seven days before or after a teleconsultation respectively, as shown in Figure 1. Instructions and a QR code were sent to the patients to download and activate FibriCheck. The code automatically links the application to an online platform available for the treating physician. Patients were asked to record their heart rhythm three times a day and when they experienced symptoms. Results In total, 92 patients (mean age: 64.7 ± 17.4) were contacted during the first COVID-19 peak, of which a total of 22 patients declined because not owing a smartphone or tablet (n = 11) or they were not willing or not capable to use FibriCheck (n = 11). A significant age difference was seen between the 22 non-participants versus the 70 participants (mean age 73.8 ± 18.7 vs. 61.9 ± 15.9; p = 0.004). Half of the patients, eligible for PPG monitoring (n = 38, 54.9%), were initiated before a planned (tele)consultation. Of these, four patients (10.5%) were diagnosed with an arrhythmia by using FibriCheck, of which two had frequent extrasystoles and two had a recurrence of AF and rate control was adapted. Of the 32 patients who used FibriCheck after a teleconsultation due to symptomatic palpitations, extrasystoles (n = 3) or high suspicion for a new AF diagnosis (n = 2) was established via FibriCheck. Early in-office evaluation was organised for the patients with a new diagnosis of AF, and rhythm control was initiated. In the majority of patients (57.1%), teleconsultation with FibriCheck was reassuring so that they could be followed-up according to their normal schedule. Conclusion During the COVID-19 pandemic, cardiologists were able to obtain important additional information using the FibriCheck application when performing teleconsultations. The possibility to successfully complete teleconsultations using the FibriCheck data, and its broad applicability, create opportunities to implement FibriCheck in standard clinical practice as an easy tool to monitor patients before or after in-person consultations or even hospitalisations.

Published
2021
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36. Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease

Author

Michela Traglia, Tom Forsén, Stefano Mariotti, Giorgio Pistis, Katharina Schramm, Jayne A. Franklyn, Suzanne J. Brown, Jürgen Kratzsch, Christian Gieger, W. Edward Visser, Matteo Vocale, Fred C.G.J. Sweep, Daniel Tiller, Anne R. Cappola, Massimiliano Cocca, Johannes W. A. Smit, Johan G. Eriksson, Peter O'Leary, Diana Pietzner, Lise Lotte N. Husemoen, Silvia Naitza, Peter J. Leedman, Alexander Hamilton, Hans J. Grabe, Ee Mun Lim, Jennie Hui, Beverley M. Shields, Allan Linneberg, Richard A. Jensen, Tim De Meyer, Stephen C. L. Gough, Layal Chaker, Henriette E. Meyer zu Schwabedissen, Matthew J. Simmonds, Alice M. Arnold, Marco Medici, Alexandra Bremner, Monia Lobina, Linda Broer, Theo S. Plantinga, Huiling He, Ad R. M. M. Hermus, Eero Kajantie, Daniela Toniolo, Rebecca Nagy, Sita H. Vermeulen, Eva Reischl, Romana T. Netea-Maier, John Beilby, Tessel E. Galesloot, Tim I M Korevaar, Fernando Rivadeneira, Henri Wallaschofski, Peter Feddema, Margit Heier, Uwe Völker, David Schlessinger, J. Brent Richards, Christa Meisinger, Gonçalo R. Abecasis, Rachel M. Freathy, Alessandro P Delitala, Theo J. Visser, Georg Homuth, Corrado Masciullo, Aarno Palotie, Timothy M. Frayling, Elisabeth Widen, Matthias Nauck, Till Ittermann, Betina H. Thuesen, Christin Spielhagen, Jari Lahti, W. G. Li, Nicola Pirastu, Tanguy Corre, Alan James, Lambertus A. Kiemeney, Cinzia Sala, Sandya Liyanarachchi, Bijay Vaidya, Jerome I. Rotter, Jean-Marc Kaufman, Rajesh Rawal, Albert Hofman, Alexander Teumer, Ernst E. Rietzschel, Robin P. Peeters, Henry Völzke, Serena Sanna, John P. Walsh, Greet Roef, Holger Prokisch, Albert de la Chapelle, Stephen J. Fletcher, Alexander Kluttig, Tim D. Spector, André G. Uitterlinden, Martin den Heijer, Alec H. Ross, Eric Wichmann, Katri Räikkönen, Yurii S. Aulchenko, Antonella Mulas, Martijn van de Bunt, David I. W. Philips, Gabriela L. Surdulescu, Andrew T. Hattersley, Dörte Radke, Scott Wilson, Maria Grazia Plia, Y. Taes, Torben Jørgensen, Nicole Soranzo, Bruce M. Psaty, Sandra Lai, Eleonora Porcu, Emanuele Bosi, Medici, M, Porcu, E, Pistis, G, Teumer, A, Brown, Sj, Jensen, Ra, Rawal, R, Roef, Gl, Plantinga, T, Vermeulen, Sh, Lahti, J, Simmonds, Mj, Husemoen, Ll, Freathy, Rm, Shields, Bm, Pietzner, D, Nagy, R, Broer, L, Chaker, L, Korevaar, Ti, Plia, Mg, Sala, C, Völker, U, Richards, Jb, Sweep, Fc, Gieger, C, Corre, T, Kajantie, E, Thuesen, B, Taes, Ye, Visser, We, Hattersley, At, Kratzsch, J, Hamilton, A, Li, W, Homuth, G, Lobina, M, Mariotti, S, Soranzo, N, Cocca, Massimiliano, Nauck, M, Spielhagen, C, Ross, A, Arnold, A, van de Bunt, M, Liyanarachchi, S, Heier, M, Grabe, Hj, Masciullo, C, Galesloot, Te, Lim, Em, Reischl, E, Leedman, Pj, Lai, S, Delitala, A, Bremner, Ap, Philips, Di, Beilby, Jp, Mulas, A, Vocale, M, Abecasis, G, Forsen, T, James, A, Widen, E, Hui, J, Prokisch, H, Rietzschel, Ee, Palotie, A, Feddema, P, Fletcher, Sj, Schramm, K, Rotter, Ji, Kluttig, A, Radke, D, Traglia, Michela, Surdulescu, Gl, He, H, Franklyn, Ja, Tiller, D, Vaidya, B, de Meyer, T, Jørgensen, T, Eriksson, Jg, O'Leary, Pc, Wichmann, E, Hermus, Ar, Psaty, Bm, Ittermann, T, Hofman, A, Bosi, E, Schlessinger, D, Wallaschofski, H, Pirastu, Nicola, Aulchenko, Y, de la Chapelle, A, Netea Maier, Rt, Gough, Sc, Meyer Zu Schwabedissen, H, Frayling, Tm, Kaufman, Jm, Linneberg, A, Räikkönen, K, Smit, Jw, Kiemeney, La, Rivadeneira, F, Uitterlinden, Ag, Walsh, Jp, Meisinger, C, den Heijer, M, Visser, Tj, Spector, Td, Wilson, Sg, Völzke, H, Cappola, A, Toniolo, D, Sanna, S, Naitza, S, Peeters, R. p. 1., Cocca, M, Traglia, M, Bosi, Emanuele, Pirastu, N, Peeters, Rp, Internal medicine, EMGO - Lifestyle, overweight and diabetes, Internal Medicine, Epidemiology, Cardiology, Clinical Genetics, Behavioural Sciences, Children's Hospital, Lastentautien yksikkö, Clinicum, Institute for Molecular Medicine Finland, Department of General Practice and Primary Health Care, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, and Genomic Discoveries and Clinical Translation

Subjects
Cancer Research, Goiter, endocrine system diseases, Graves' disease, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Thyrotropin, Gastroenterology, thyroid, GRAVES-DISEASE, Endocrinology, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Hashimoto Disease, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Thyroid cancer, Genetics (clinical), 0303 health sciences, Thyroid disease, Thyroid, IODIDE ORGANIFICATION DEFECTS, COMMON VARIANTS, Graves Disease, 3. Good health, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], medicine.anatomical_structure, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Medicine, HEART-FAILURE, Research Article, medicine.medical_specialty, endocrine system, lcsh:QH426-470, SUSCEPTIBILITY LOCI, 515 Psychology, education, 030209 endocrinology & metabolism, Biology, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Iodide Peroxidase, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, Hypothyroidism, SDG 3 - Good Health and Well-being, Thyroid peroxidase, Internal medicine, Genetics, medicine, Humans, ddc:610, Risk factor, GENOME-WIDE ASSOCIATION, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Autoantibodies, 030304 developmental biology, WHICKHAM SURVEY, Thyroiditis, Autoimmune, medicine.disease, C420 Human Genetics, RHEUMATOID-ARTHRITIS, meta-analysis, lcsh:Genetics, meta-analysis, thyroid, Genetic Loci, Graves' Disease, FEMALE RELATIVES, Immunology, biology.protein, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], 3111 Biomedicine, Genome-Wide Association Study
Abstract

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P, Author Summary Individuals with thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune thyroid diseases (AITD), which are common in the general population and associated with increased cardiovascular, metabolic and psychiatric morbidity and mortality. As the causative genes of TPOAbs and AITD remain largely unknown, we performed a genome-wide scan for TPOAbs in 18,297 individuals, with replication in 8,990 individuals. Significant associations were detected with variants at TPO, ATXN2, BACH2, MAGI3, and KALRN. Individuals carrying multiple risk variants also had a higher risk of increased thyroid-stimulating hormone levels (including subclinical and overt hypothyroidism), and a decreased risk of goiter. The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, and the MAGI3 variant was also associated with an increased risk of hypothyroidism. This first genome-wide scan for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. These results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which individuals are particularly at risk of developing clinical thyroid dysfunction.

Published
2014
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37. Independent Genetic Mapping Experiments Identify Diverse Molecular Determinants of Host Adaptation in a Generalist Herbivore.

Author

Villacis-Perez E, De Graeve F, De Beer B, Ali Alshami S, De Jong R, De Meyer T, and Van Leeuwen T

Abstract

Interactions between plants and herbivores promote evolutionary change. Studying the evolution of herbivore mechanisms aimed to cope with different host plant species is a critical intersection between evolutionary biology and sustainable pest management. Generalist herbivores are of particular interest, as hybridization between genetically distinct populations can increase the standing genetic variation and therefore the adaptive potential of the species. Tetranychus urticae is a generalist arthropod known for its adaptive potential, evidenced in its immense host range and ability to develop metabolic resistance to xenobiotics. However, the molecular underpinnings associated with the potential of host adaptation and the consequences of host adaptation in this, and many other pests remain elusive. Here, we use two independent, empirical approaches to identify and map the genetic basis of host plant performance and adaptation in genetically distinct populations of T. urticae. In the first approach, we subject a genetically diverse mite population to tomato selection and map genomic regions linked to the phenotypic evolution of increased reproductive performance. In the second approach, we map genomic regions responsible for performance on tomato by comparing the genomes of pooled individuals from an F2 backcross between populations with high and low reproductive performance. Both approaches revealed specific and shared genomic regions associated with host plant performance and adaptation and key candidate genes were identified. Our findings highlight the power of spider mite genetic approaches to identify the complex genetic basis of host adaptation in generalist herbivores., (© 2024 John Wiley & Sons Ltd.)

Published
2024
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38. Characterization of Loss-of-Imprinting in Breast Cancer at the Cellular Level by Integrating Single-Cell Full-Length Transcriptome with Bulk RNA-Seq Data.

Author

Amin MT, Coussement L, and De Meyer T

Subjects
Humans, Female, RNA-Seq methods, Gene Expression Regulation, Neoplastic, Sequence Analysis, RNA methods, Cell Line, Tumor, Genomic Imprinting genetics, Breast Neoplasms genetics, Breast Neoplasms pathology, Single-Cell Analysis methods, Polymorphism, Single Nucleotide genetics, Transcriptome genetics
Abstract

Genomic imprinting, the parent-of-origin-specific gene expression, plays a pivotal role in growth regulation and is often dysregulated in cancer. However, screening for imprinting is complicated by its cell-type specificity, which bulk RNA-seq cannot capture. On the other hand, large-scale single-cell RNA-seq (scRNA-seq) often lacks transcript-level detail and is cost-prohibitive. Here, we address this gap by integrating bulk RNA-seq with full-length transcript scRNA-seq to investigate imprinting dynamics in breast cancer. By analyzing scRNA-seq data from 486 cancer cells across subtypes, we identified multiple SNPs in imprinted genes, including HM13 , MEST ( PEG1 ), SNHG14 and PEG10 , showing consistent biallelic expression. Bulk RNA-seq, however, revealed that this biallelic expression arises from transcript-specific imprinting, rather than loss-of-imprinting (LOI). The imprinted SNPs identified in bulk RNA-seq predominantly demonstrate proper monoallelic expression in scRNA-seq. As a clear exception, an HER2+ breast cancer sample exhibited distinct LOI of MEST . Previous bulk RNA-seq-based observations about MEST LOI in breast cancer could not exclude a non-cancer cell impact, but our results validate that MEST LOI is cancer-specific. This study demonstrates the complementary utility of bulk and scRNA-seq in imprinting studies, confirming MEST LOI as a genuine event in breast cancer.

Published
2024
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39. Overexpression of the ribosome-inactivating protein OsRIP1 modulates the jasmonate signaling pathway in rice.

Author

Chen S, De Zutter N, Meijer A, Gistelinck K, Wytynck P, Verbeke I, Osterne VJS, Kondeti S, De Meyer T, Audenaert K, and Van Damme EJM

Abstract

Ribosome-inactivating proteins (RIPs) are plant enzymes that target the rRNA. The cytoplasmic RIP, called OsRIP1, plays a crucial role in regulating jasmonate, a key plant hormone. Understanding the role of OsRIP1 can provide insights into enhancing stress tolerance and optimizing growth of rice. Transcription profiling by mRNA sequencing was employed to measure the changes in gene expression in rice plants in response to MeJA treatment. Compared to wild type (WT) plants, OsRIP1 overexpressing rice plants showed a lower increase in mRNA transcripts for genes related to jasmonate responses when exposed to MeJA treatment for 3 h. After 24 h of MeJA exposure, the mRNA transcripts associated with the gibberellin pathway occurred in lower levels in OsRIP1 overexpressing plants compared to WT plants. We hypothesize that the mechanism underlying OsRIP1 antagonization of MeJA-induced shoot growth inhibition involves cytokinin-mediated leaf senescence and positive regulation of cell cycle processes, probably via OsRIP1 interaction with 40S ribosomal protein S5 and α-tubulin. Moreover, the photosystem II 10kDa polypeptide was identified to favorably bind to OsRIP1, and its involvement may be attributed to the reduction of photosynthesis in OsRIP1 -overexpressing plants subjected to MeJA at the early timepoint (3 h)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Chen, De Zutter, Meijer, Gistelinck, Wytynck, Verbeke, Osterne, Kondeti, De Meyer, Audenaert and Van Damme.)

Published
2024
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40. Loss-of-Imprinting of HM13 Leads to Poor Prognosis in Clear Cell Renal Cell Carcinoma.

Author

Voorthuijzen F, Stroobandt C, Van Criekinge W, Goovaerts T, and De Meyer T

Subjects
Humans, Female, Male, Prognosis, Middle Aged, Gene Expression Regulation, Neoplastic, Insulin-Like Growth Factor II genetics, Insulin-Like Growth Factor II metabolism, Aged, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell pathology, Carcinoma, Renal Cell metabolism, Carcinoma, Renal Cell mortality, Kidney Neoplasms genetics, Kidney Neoplasms pathology, Kidney Neoplasms metabolism, Kidney Neoplasms mortality, Genomic Imprinting
Abstract

Genomic imprinting refers to the epigenetic silencing of one of both alleles in a parent-of-origin-specific manner, particularly in genes regulating growth and development. Impaired genomic imprinting leading to the activation of the silenced allele, also called canonical loss-of-imprinting (LOI), is considered an early factor in oncogenesis. As LOI studies in clear cell renal cell carcinoma (ccRCC) are limited to IGF2 , we performed a genome-wide analysis in 128 kidney normal solid tissue and 240 stage 1 ccRCC samples (TCGA RNA-seq data) to screen for canonical LOI in early oncogenesis. In ccRCC, we observed LOI (adj. p = 2.74 × 10 -3 ) of HM13 (Histocompatibility Minor 13), a signal peptide peptidase involved in epitope generation. HM13 LOI samples featured HM13 overexpression, both compared to normal solid tissues ( p = 3.00 × 10 -7 ) and non-LOI ( p = 1.27 × 10 -2 ) samples. Upon adjustment for age and sex, HM13 expression was significantly associated with poor survival ( p = 7.10 × 10 -5 ). Moreover, HM13 overexpression consistently exacerbated with increasing tumor stage ( p = 2.90 × 10 -8 ). For IGF2 , LOI was observed in normal solid tissues, but the prevalence did not increase in cancer. In conclusion, HM13 LOI is an early event in ccRCC, causing overexpression leading to poor prognosis.

Published
2024
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41. Quantitative transcriptomic and epigenomic data analysis: a primer.

Author

Coussement L, Van Criekinge W, and De Meyer T

Abstract

The advent of microarray and second generation sequencing technology has revolutionized the field of molecular biology, allowing researchers to quantitatively assess transcriptomic and epigenomic features in a comprehensive and cost-efficient manner. Moreover, technical advancements have pushed the resolution of these sequencing techniques to the single cell level. As a result, the bottleneck of molecular biology research has shifted from the bench to the subsequent omics data analysis. Even though most methodologies share the same general strategy, state-of-the-art literature typically focuses on data type specific approaches and already assumes expert knowledge. Here, however, we aim at providing conceptual insight in the principles of genome-wide quantitative transcriptomic and epigenomic (including open chromatin assay) data analysis by describing a generic workflow. By starting from a general framework and its assumptions, the need for alternative or additional data-analytical solutions when working with specific data types becomes clear, and are hence introduced. Thus, we aim to enable readers with basic omics expertise to deepen their conceptual and statistical understanding of general strategies and pitfalls in omics data analysis and to facilitate subsequent progression to more specialized literature., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Published
2024
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42. The phenylalanine ammonia-lyase inhibitor AIP induces rice defence against the root-knot nematode Meloidogyne graminicola.

Author

Liu J, Lefevere H, Coussement L, Delaere I, De Meyer T, Demeestere K, Höfte M, Gershenzon J, Ullah C, and Gheysen G

Subjects
Animals, Phenylalanine Ammonia-Lyase genetics, Phenylalanine Ammonia-Lyase metabolism, Cyclopentanes pharmacology, Cyclopentanes metabolism, Oryza genetics, Oryza metabolism, Tylenchoidea physiology, Oxylipins
Abstract

The phenylalanine ammonia-lyase (PAL) enzyme catalyses the conversion of l-phenylalanine to trans-cinnamic acid. This conversion is the first step in phenylpropanoid biosynthesis in plants. The phenylpropanoid pathway produces diverse plant metabolites that play essential roles in various processes, including structural support and defence. Previous studies have shown that mutation of the PAL genes enhances disease susceptibility. Here, we investigated the functions of the rice PAL genes using 2-aminoindan-2-phosphonic acid (AIP), a strong competitive inhibitor of PAL enzymes. We show that the application of AIP can significantly reduce the PAL activity of rice crude protein extracts in vitro. However, when AIP was applied to intact rice plants, it reduced infection of the root-knot nematode Meloidogyne graminicola. RNA-seq showed that AIP treatment resulted in a rapid but transient upregulation of defence-related genes in roots. Moreover, targeted metabolomics demonstrated higher levels of jasmonates and antimicrobial flavonoids and diterpenoids accumulating after AIP treatment. Furthermore, chemical inhibition of the jasmonate pathway abolished the effect of AIP on nematode infection. Our results show that disturbance of the phenylpropanoid pathway by the PAL inhibitor AIP induces defence in rice against M. graminicola by activating jasmonate-mediated defence., (© 2024 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Published
2024
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43. Concurrent invasions of European starlings in Australia and North America reveal population-specific differentiation in shared genomic regions.

Author

Hofmeister NR, Stuart KC, Warren WC, Werner SJ, Bateson M, Ball GF, Buchanan KL, Burt DW, Cardilini APA, Cassey P, De Meyer T, George J, Meddle SL, Rowland HM, Sherman CDH, Sherwin WB, Vanden Berghe W, Rollins LA, and Clayton DF

Abstract

A species' success during the invasion of new areas hinges on an interplay between the demographic processes common to invasions and the specific ecological context of the novel environment. Evolutionary genetic studies of invasive species can investigate how genetic bottlenecks and ecological conditions shape genetic variation in invasions, and our study pairs two invasive populations that are hypothesized to be from the same source population to compare how each population evolved during and after introduction. Invasive European starlings (Sturnus vulgaris) established populations in both Australia and North America in the 19th century. Here, we compare whole-genome sequences among native and independently introduced European starling populations to determine how demographic processes interact with rapid evolution to generate similar genetic patterns in these recent and replicated invasions. Demographic models indicate that both invasive populations experienced genetic bottlenecks as expected based on invasion history, and we find that specific genomic regions have differentiated even on this short evolutionary timescale. Despite genetic bottlenecks, we suggest that genetic drift alone cannot explain differentiation in at least two of these regions. The demographic boom intrinsic to many invasions as well as potential inversions may have led to high population-specific differentiation, although the patterns of genetic variation are also consistent with the hypothesis that this infamous and highly mobile invader adapted to novel selection (e.g., extrinsic factors). We use targeted sampling of replicated invasions to identify and evaluate support for multiple, interacting evolutionary mechanisms that lead to differentiation during the invasion process., (© 2023 John Wiley & Sons Ltd.)

Published
2023
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44. Dicer-like 3a mediates intergenerational resistance against root-knot nematodes in rice via hormone responses.

Author

Meijer A, Atighi MR, Demeestere K, De Meyer T, Vandepoele K, and Kyndt T

Subjects
Animals, Plant Diseases genetics, Plant Diseases parasitology, Ethylenes metabolism, Hormones metabolism, Plant Roots metabolism, Oryza metabolism, Tylenchoidea physiology
Abstract

In a continuously changing and challenging environment, passing down the memory of encountered stress factors to offspring could provide an evolutionary advantage. In this study, we demonstrate the existence of "intergenerational acquired resistance" in the progeny of rice (Oryza sativa) plants attacked by the belowground parasitic nematode Meloidogyne graminicola. Transcriptome analyses revealed that genes involved in defense pathways are generally downregulated in progeny of nematode-infected plants under uninfected conditions but show a stronger induction upon nematode infection. This phenomenon was termed "spring loading" and depends on initial downregulation by the 24-nucleotide (nt) siRNA biogenesis gene dicer-like 3a (dcl3a) involved in the RNA-directed DNA methylation pathway. Knockdown of dcl3a led to increased nematode susceptibility and abolished intergenerational acquired resistance, as well as jasmonic acid/ethylene spring loading in the offspring of infected plants. The importance of ethylene signaling in intergenerational resistance was confirmed by experiments on a knockdown line of ethylene insensitive 2 (ein2b), which lacks intergenerational acquired resistance. Taken together, these data indicate a role for DCL3a in regulating plant defense pathways during both within-generation and intergenerational resistance against nematodes in rice., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2023
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45. Promoter hypermethylation of neural-related genes is compatible with stemness in solid cancers.

Author

Idris M, Coussement L, Alves MM, De Meyer T, and Melotte V

Subjects
Humans, DNA, DNA Methylation, Colonic Neoplasms genetics
Abstract

Background: DNA hypermethylation is an epigenetic feature that modulates gene expression, and its deregulation is observed in cancer. Previously, we identified a neural-related DNA hypermethylation fingerprint in colon cancer, where most of the top hypermethylated and downregulated genes have known functions in the nervous system. To evaluate the presence of this signature and its relevance to carcinogenesis in general, we considered 16 solid cancer types available in The Cancer Genome Atlas (TCGA)., Results: All tested cancers showed significant enrichment for neural-related genes amongst hypermethylated genes. This signature was already present in two premalignant tissue types and could not be explained by potential confounders such as bivalency status or tumor purity. Further characterization of the neural-related DNA hypermethylation signature in colon cancer showed particular enrichment for genes that are overexpressed during neural differentiation. Lastly, an analysis of upstream regulators identified RE1-Silencing Transcription factor (REST) as a potential mediator of this DNA methylation signature., Conclusion: Our study confirms the presence of a neural-related DNA hypermethylation fingerprint in various cancers, of genes linked to neural differentiation, and points to REST as a possible regulator of this mechanism. We propose that this fingerprint indicates an involvement of DNA hypermethylation in the preservation of neural stemness in cancer cells., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Published
2023
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46. Liver transcriptomic and methylomic analyses identify transcriptional mitogen-activated protein kinase regulation in facultative hibernation of Syrian hamster.

Author

Coussement L, Oosterhof MM, Guryev V, Reitsema VA, Bruintjes JJ, Goris M, Bouma HR, de Meyer T, Rots MG, and Henning RH

Subjects
Animals, Cricetinae, Mesocricetus, Liver, Gene Expression Profiling, Transcriptome, Hibernation
Abstract

Hibernation consists of alternating torpor-arousal phases, during which animals cope with repetitive hypothermia and ischaemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole-genome bisulfide sequencing in liver of hibernating Syrian hamster ( Mesocricetus auratus ). Gene ontology analysis was performed on 844 differentially expressed genes and confirmed the shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. Additionally, we showed a so far unreported suppression of mitogen-activated protein kinase (MAPK) and protein phosphatase 1 pathways during torpor. Notably, hibernating hamsters showed upregulation of MAPK inhibitors (dual-specificity phosphatases and sproutys) and reduced levels of MAPK-induced transcription factors (TFs). Promoter methylation was found to modulate the expression of genes targeted by these TFs. In conclusion, we document gene regulation between hibernation phases, which may aid the identification of pathways and targets to prevent organ damage in transplantation or ischaemia-reperfusion.

Published
2023
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47. Diproline-induced resistance to parasitic nematodes in the same and subsequent rice generations: Roles of iron, nitric oxide and ethylene.

Author

De Kesel J, Bonneure E, Frei M, De Meyer T, Mangelinckx S, and Kyndt T

Abstract

Induced resistance (IR) is a plant phenotype characterized by lower susceptibility to biotic challenges upon elicitation by so-called IR stimuli. Earlier, we identified diproline ( cyclo (l-Pro-l-Pro)) as IR stimulus that protects rice ( Oryza sativa ) against the root-knot nematode Meloidogyne graminicola ( Mg ). In the current study, detailed transcriptome analyses at different time points, and under uninfected and nematode-infected conditions revealed that this rice IR phenotype is correlated with induction of genes related to iron (Fe), ethylene (ET) and reactive oxygen species (ROS)/reactive nitrogen species (RNS) metabolism. An infection experiment under Fe limiting conditions confirmed that diproline-IR is only effective under optimal Fe supply. Although total root Fe levels were not affected in diproline-treated plants, phytosiderophore secretion was found to be induced by this treatment. Experiments on mutant and transgenic rice lines impaired in ET or ROS/RNS metabolism confirmed that these metabolites are involved in diproline-IR. Finally, we provide evidence for transgenerational inheritance of diproline-IR (diproline-TIR), as two successive generations of diproline-treated ancestors exhibited an IR phenotype while themselves never being exposed to diproline. Transcriptome analyses on the offspring plants revealed extensive overlap between the pathways underpinning diproline-IR and diproline-TIR. Although diproline induces significant systemic changes in global DNA methylation levels early after treatment, such changes in DNA methylation were not detected in the descendants of these plants. To our knowledge, this is the first report of TIR in rice and the first transcriptional assessment of TIR in monocots., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 De Kesel, Bonneure, Frei, De Meyer, Mangelinckx and Kyndt.)

Published
2023
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48. Trans-driven variation in expression is common among detoxification genes in the extreme generalist herbivore Tetranychus urticae.

Author

Kurlovs AH, De Beer B, Ji M, Vandenhole M, De Meyer T, Feyereisen R, Clark RM, and Van Leeuwen T

Subjects
Animals, Herbivory, Gene Transfer, Horizontal, Adaptation, Physiological, Plants, Tetranychidae genetics, Pesticides
Abstract

The extreme adaptation potential of the generalist herbivore Tetranychus urticae (the two-spotted spider mite) to pesticides as well as diverse host plants has been associated with clade-specific gene expansions in known detoxifying enzyme families, and with extensive and rapid transcriptional responses. However, how this broad transcriptional potential is regulated remains largely unknown. Using a parental/F1 design in which four inbred strains were crossed to a common inbred strain, we assessed the genetic basis and inheritance of gene expression variation in T. urticae. Mirroring known phenotypic variation in the progenitor strains of the inbreds, we confirmed that the inbred strains we created were genetically distinct, varied markedly in pesticide resistance, and also captured variation in host plant fitness as is commonly observed in this species. By examining differences in gene expression between parents and allele-specific expression in F1s, we found that variation in RNA abundance was more often explained in trans as compared to cis, with the former associated with dominance in inheritance. Strikingly, in a gene ontology analysis, detoxification genes of the cytochrome P450 monooxygenase (CYP) family, as well as dioxygenases (DOGs) acquired from horizontal gene transfer from fungi, were specifically enriched at the extremes of trans-driven up- and downregulation. In particular, multiple CYPs and DOGs with broad substrate-specificities for pesticides or plant specialized compounds were exceptionally highly upregulated as a result of trans-regulatory variation, or in some cases synergism of cis and trans, in the most multi-pesticide resistant strains. Collectively, our findings highlight the potential importance of trans-driven expression variation in genes associated with xenobiotic metabolism and host plant use for rapid adaptation in T. urticae, and also suggests modular control of these genes, a regulatory architecture that might ameliorate negative pleiotropic effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kurlovs et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2022
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49. Transcript- and annotation-guided genome assembly of the European starling.

Author

Stuart KC, Edwards RJ, Cheng Y, Warren WC, Burt DW, Sherwin WB, Hofmeister NR, Werner SJ, Ball GF, Bateson M, Brandley MC, Buchanan KL, Cassey P, Clayton DF, De Meyer T, Meddle SL, and Rollins LA

Subjects
Animals, Australia, Genome genetics, Genomics, Molecular Sequence Annotation, Starlings genetics
Abstract

The European starling, Sturnus vulgaris, is an ecologically significant, globally invasive avian species that is also suffering from a major decline in its native range. Here, we present the genome assembly and long-read transcriptome of an Australian-sourced European starling (S. vulgaris vAU), and a second, North American, short-read genome assembly (S. vulgaris vNA), as complementary reference genomes for population genetic and evolutionary characterization. S. vulgaris vAU combined 10× genomics linked-reads, low-coverage Nanopore sequencing, and PacBio Iso-Seq full-length transcript scaffolding to generate a 1050 Mb assembly on 6222 scaffolds (7.6 Mb scaffold N50, 94.6% busco completeness). Further scaffolding against the high-quality zebra finch (Taeniopygia guttata) genome assigned 98.6% of the assembly to 32 putative nuclear chromosome scaffolds. Species-specific transcript mapping and gene annotation revealed good gene-level assembly and high functional completeness. Using S. vulgaris vAU, we demonstrate how the multifunctional use of PacBio Iso-Seq transcript data and complementary homology-based annotation of sequential assembly steps (assessed using a new tool, saaga) can be used to assess, inform, and validate assembly workflow decisions. We also highlight some counterintuitive behaviour in traditional busco metrics, and present buscomp, a complementary tool for assembly comparison designed to be robust to differences in assembly size and base-calling quality. This work expands our knowledge of avian genomes and the available toolkit for assessing and improving genome quality. The new genomic resources presented will facilitate further global genomic and transcriptomic analysis on this ecologically important species., (© 2022 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Published
2022
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50. Dehydroascorbate induces plant resistance in rice against root-knot nematode Meloidogyne graminicola.

Author

Chavan SN, De Kesel J, Desmedt W, Degroote E, Singh RR, Nguyen GT, Demeestere K, De Meyer T, and Kyndt T

Subjects
Animals, Hormones metabolism, Plant Diseases genetics, Plant Roots genetics, Reactive Oxygen Species metabolism, Salicylic Acid metabolism, Oryza genetics, Oryza metabolism, Tylenchoidea physiology
Abstract

Ascorbic acid (AsA) is an important antioxidant in plants and regulates various physiological processes. In this study, we show that exogenous treatments with the oxidized form of AsA, that is, dehydroascorbate (DHA), activates induced systemic resistance in rice against the root-knot nematode Meloidogyne graminicola, and investigate the molecular and biochemical mechanisms underlying this phenotype. Detailed transcriptome analysis on roots of rice plants showed an early and robust transcriptional response on foliar DHA treatment, with induction of several genes related to plant stress responses, immunity, antioxidant activity, and secondary metabolism already at 1 day after treatment. Quantitative and qualitative evaluation of H 2 O 2 levels confirmed the appearance of a reactive oxygen species (ROS) burst on DHA treatment, both at the site of treatment and systemically. Experiments using chemical ROS inhibitors or scavengers confirmed that H 2 O 2 accumulation contributes to DHA-based induced resistance. Furthermore, hormone measurements in DHA-treated plants showed a significant systemic accumulation of the defence hormone salicylic acid (SA). The role of the SA pathway in DHA-based induced resistance was confirmed by nematode infection experiments using an SA-signalling deficient WRKY45-RNAi line and reverse transcription-quantitative PCR on SA marker genes. Our results collectively reveal that DHA activates induced systemic resistance in rice against the root-knot nematode M. graminicola, mediated through the production of ROS and activation of the SA pathway., (© 2022 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Published
2022
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