Rheumatoid Arthritis Responder Challenge

Created By Lara Mangravite LaraMangravite
The goal of this project is to use a crowd-based competition framework to develop a validated molecular predictor of anti-TNF response in RA. There is an increasing need for predictors of response to therapy in inflammatory disease driven by the observation that most clinically defined diseases show variable response and the growing availability of alternative therapies. Anti-TNF drugs in Rheumatoid Arthritis represent a prototypical example of this opportunity. A number of studies have tried, over the past decade, to develop a robust predictor of response. We believe the time is right to try a different approach to developing such a biomarker with a crowd-sourced collaborative competition. This is based on DREAM and Sage Bionetworks' experience with running competitions and the availability of new unpublished large-scale data relating to RA treatment response.THIS CHALLENGE RAN FROM FEBRUARY TO OCTOBER 2014 AND IS NOW CLOSED. We invite you to participate in this Challenge to develop the best possible predictor of anti-TNF response. You will specifically be asked to answer one or both of the following questions: Subchallenge 1: Predict treatment response as measured by the change in disease activity score (DAS28) in response to anti-TNF therapy. Subchallenge 2: Identify poor responders as defined by EULAR criteria for non-response (~20%% of the study population). Challenge Progress Subchallenge 1 Top 5 Teams teamRank teams submitterUserName #scoredSubmissions last-submission best-leaderboard-rank 1 GuanLab, fanzhu, Guanlab, Guanlab_UMich fanzhu 391 2014-06-03 1.0 2 STSI, stsi, reboot6, reboot7, vif100 erickramer 81 2014-06-04 33.0 3 teamMI, FIN&AL audmu 749 2014-06-04 57.0 4 wtwt5237, qbrc wtwt5237 115 2014-05-25 90.0 5 KYN, kyn, ARG kyn 53 2014-04-29 113.0 Subchallenge 2 Top 5 Teams teamRank teams submitterUserName #scoredSubmissions last-submission best-leaderboard-rank 1 Guanlab, Guanlab_UMich, GuanLab fanzhu 68 2014-06-03 1.0 2 SBI_Lab javier.garciag 8 2014-06-04 16.0 3 wtwt5237, qbrc wtwt5237 44 2014-05-25 16.0 4 outliers, bowang87 bowang87 46 2014-06-04 19.0 5 teamMI, FIN&AL audmu 150 2014-06-03 35.0 REGISTRATION AND DATA ACCESS APPROVAL FOR THIS CHALLENGE IS CURRENTLY OPEN. Please view the registration and data access pages for more information. Please note that you have to complete both the registration and the data access request processes before you will be able to view or download the training data files. This is due to the sensitive nature of the data provided within this Challenge. Should you have any questions related to this Challenge, please visit our Rheumatoid Arthritis Responder Challenge Community Forum. Challenge organizers will be posting information and answering questions on the forum. You may review the DREAM8.5 Challenge rules here: syn2295117 Challenge Overview:Participants will be provided with whole genome genotype data (~2.2 million SNPs) and clinical data collected from ~2,700 RA individuals that have been treated with anti-TNF therapy. This dataset was generated by a collaborative group of rheumatologists and has been described in detail in the scientific literature. Preliminary analysis of this data suggests there is signal, with one SNP at the CD84 locus approaching genome-wide significance. Unpublished results include additional suggestive associations, and a polygenic linear mixed model analysis indicating that in aggregate imputed SNPs explain 15-20% of the variance of TNF response, and greater than 30% in patients treated with infliximab or adalimumab. Your mission will be to use these data to create a predictive model of treatment response. In addition to the training data, we will also provide you with several ancillary datasets that may be helpful in model design including: (1) RNAseq-based transcriptional profiles and genotypes collected from 30 patients with severe disease and 30 patients with mild disease and (2) cellular TNF concentrations and whole-genome genotype data collected from 220 lymphoblastoid cell lines. Final predictions will be tested using a second dataset containing whole genome genotype data and clinical data collected from a second cohort of ~700 RA patients treated with anti-TNF therapy. These data, collected as part of the CORRONA-CERTAIN trial, were generated specifically for use in testing models developed within this Challenge. Participation:Registration for this Challenge opened on November 8, 2013 and registered participants are free to request access to the data (see instructions below). The Challenge will open on February 10, 2014 and complete later this year. Because the data access approval process may take a few days, we encourage participants to begin this process as soon as possible. Journal Partner:In this Challenge, the Challenge organizers are working with Nature Genetics to assess the utility of the Challenge-framework in enabling effective peer-review during development of computational biology algorithms. Nature Genetics is involved in the development of this Challenge and will be observing community-participation and analytical outcomes. Data Generators:The training data available through this project was generated by the International Rheumatoid Arthritis Consortium (INTERACT), which includes the following members: Jing Cui 1, Eli A. Stahl 1-3, 7, Saedis Saevarsdottir 4,5, Corinne Miceli 6, Dorothee Diogo 1-3, Ma?a Umi?evi? Mirkov 8, Helena Canhao 1,9,10, Katsunori Ikari 11, Chikashi Terao 12,13, Yukinori Okada 1-3, Sara Wedrn 4,5, Johan Askling 4,14, Hisashi Yamanaka 11, Shigeki Momohara 11, Atsuo Taniguchi 11, Koichiro Ohmura 12, Fumihiko Matsuda 13, Tsuneyo Mimori 12, Namrata Gupta 3, Manik Kuchroo 3,7, Ann W. Morgan 15, John D. Isaacs 16, Anthony G. Wilson 17, Kimme L. Hyrich 18, Marieke Herenius 19, Marieke E Doorenspleet 19, Paul-Peter Tak 19#, J Bart A Crusius 20, Irene E van der Horst-Bruinsma 21, Gert Jan Wolbink 22,23, Piet LCM van Riel 8, Mart van de Laar 24, Henk-Jan Guchelaar 25, Nancy A. Shadick 1, Cornelia F. Allaart 26, Tom W. J. Huizinga 26, Rene E M Toes 26, Robert P. Kimberly 27, S. Louis Bridges, Jr. 27, Lindsey A. Criswell 28, Larry W. Moreland 29, Joo Eurico Fonseca 9,10, Niek de Vries 19, Soumya Raychaudhuri 1-3, 30, Michael E. Weinblatt 1, Peter K. Gregersen 31, Xavier Mariette 6, Anne Barton 32, Lars Alfredsson 5, Lars Klareskog 4, Leonid Padyukov 4, Marieke JH Coenen 8, Elizabeth W. Karlson 1, Joel Kremer 33, Jeffrey D. Greenberg 33,34, Robert M. Plenge 1-3 Affiliations: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA.^ EAS Currently: Division of Psychiatric Genomics, Mt Sinai School of Medicine, New York, New York, 10029, USA. Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA. Medical and Population Genetics Program, Chemical Biology Program, Broad Institute, Cambridge, Massachusetts, 02142, USA. Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden University Paris-Sud, AP-HP, hospital Bictre, INSERM U1012 Division of Psychiatric Genomics and Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mt. Sinai, New York, New York, 10029, USA Department of Human Genetics, Radboud University Medical Centre, PO box 9101, 6500 HB Nijmegen, The Netherlands Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon Rheumatology Department, Santa Maria Hospital CHLN, Lisbon, Portugal Institute of Rheumatology, Tokyo Womens Medical University, Tokyo, Japan Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute/Karolinska University Hospital, Stockholm, Sweden. NIHR Leeds Musculoskeletal Biomedical Research Unit and Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle Upon Tyne, UK Rheumatology Unit, Medical School, University of Sheffield, Sheffield, UK School of Translational Medicine, Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK Department of Clinical Immunology & Rheumatology, AMC/University of Amsterdam, PO Box 22700, 1100DE Amsterdam, The Netherlands #Currently: GlaxoSmithKline, Stevenage, U.K Laboratory of Immunogenetics, Department of Pathology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. Department of Rheumatology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands. Sanquin Research Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. School of Medicine and Biomedical Sciences, Sheffield University, Sheffield, UK. 31Jan van Breemen Institute, Amsterdam, The Netherlands. Arthritis Center Twente, University Twente & Medisch Spectrum Twente, Enschede, The Netherlands Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, PO box 9600, 2300 RC Leiden, The Netherlands Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 Rosalind Russell Medical Research Center for Arthritis, Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA 94117 Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA 15201 NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust, Manchester Academic Health Sciences Centre, UK. The Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, New York, USA. Arthritis Research UK Epidemiology Unit, Musculoskeletal Research Group, University of Manchester, Manchester Academic Health Sciences Centre, UK. Consortium of Rheumatology Researchers of North America, Inc. (CORRONA) Division of Rheumatology, New York University School of Medicine, New York, NY, 10016, USA

RA Challenge Resources
Ancillary Data
Cross Validation Predictions