An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

Brownstein, CatherineBeggs, AlanHomer, NilsMerriman, BarryYu, Timothy WFlannery, KatherineDeChene, Elizabeth TTowne, Meghan CSavage, Sarah KPrice, Emily NHolm, IngridLuquette, JoeLyon, ElaineMajzoub, JosephNeupert, PeterMcCallie Jr, DavidSzolovits, PeterWillard, Huntington FMendelsohn, Nancy JTemme, ReneeFinkel, Richard SYum, Sabrina WMedne, LivijaSunyaev, ShamilAdzhubey, IvanCassa, Christopherde Bakker, Paul IWDuzkale, HaticeDworzyński, PiotrFairbrother, WilliamFrancioli, LaurentFunke, BirgitGiovanni, Monica AHandsaker, RobertLage, KasperLebo, MatthewLek, MonkolLeshchiner, IgnatyMacArthur, DanielMcLaughlin, Heather MMurray, Michael FPers, Tune HPolak, Paz PRaychaudhuri, SoumyaRehm, HeidiSoemedi, RachelStitziel, Nathan OVestecka, SaraSupper, JochenGugenmus, ClaudiaKlocke, BernwardHahn, AlexanderSchubach, MaxMenzel, MortizBiskup, SaskiaFreisinger, PeterDeng, MarioBraun, MartinPerner, SvenSmith, Richard JHAndorf, Janeen LHuang, JianRyckman, KelliSheffield, Val CStone, Edwin MBair, ThomasBlack-Ziegelbein, E AnnBraun, Terry ADarbro, BenjaminDeLuca, Adam PKolbe, Diana LScheetz, Todd EShearer, Aiden ESompallae, RamaWang, KaiBassuk, Alexander GEdens, ErikMathews, KatherineMoore, Steven AShchelochkov, Oleg ATrapane, PamelaBossler, AaronCampbell, Colleen AHeusel, Jonathan WKwitek, AnneMaga, TaraPanzer, KarinWassink, ThomasVan Daele, DouglasAzaiez, HelaBooth, KevinMeyer, NicSegal, Michael MWilliams, Marc STromp, GerardWhite, PeterCorsmeier, DonaldFitzgerald-Butt, SaraHerman, GailLamb-Thrush, DevonMcBride, Kim LNewsom, DavidPierson, Christopher RRakowsky, Alexander TMaver, AlešLovrečić, LucaPalandačić, AnjaPeterlin, BorutTorkamani, AliWedell, AnnaHuss, MikaelAlexeyenko, AndreyLindvall, Jessica MMagnusson, MånsNilsson, DanielStranneheim, HenrikTaylan, FulyaGilissen, ChristianHoischen, Alexandervan Bon, BregjeYntema, HelgerNelen, MarcelZhang, WeidongSager, JasonZhang, LuBlair, KathrynKural, DenizCariaso, MichaelLennon, Greg GJaved, AsifAgrawal, SaloniNg, Pauline CSandhu, Komal SKrishna, ShubaVeeramachaneni, VamsiIsakov, OferHalperin, EranFriedman, EitanShomron, NoamGlusman, GustavoRoach, Jared CCaballero, JuanCox, Hannah CMauldin, DeniseAment, Seth ARowen, LeeRichards, Daniel RLucas, F Anthony SanGonzalez-Garay, Manuel LCaskey, C ThomasBai, YuHuang, YingFang, FangZhang, YanWang, ZhengyuanBarrera, JorgeGarcia-Lobo, Juan MGonzález-Lamuño, DomingoLlorca, JavierRodriguez, Maria CVarela, IgnacioReese, Martin GDe La Vega, Francisco MKiruluta, EdwardCargill, MicheleHart, Reece KSorenson, Jon MLyon, Gholson JStevenson, David ABray, Bruce EMoore, Barry MEilbeck, KarenYandell, MarkZhao, HongyuHou, LinChen, XiaoweiYan, XitingChen, MengjieLi, CongYang, CanGunel, MuratLi, PeiningKong, YongAlexander, Austin CAlbertyn, Zayed IBoycott, Kym MBulman, Dennis EGordon, Paul MKInnes, A MicheilKnoppers, Bartha MMajewski, JacekMarshall, Christian RParboosingh, Jillian SSawyer, Sarah LSamuels, Mark ESchwartzentruber, JeremyKohane, IsaacMargulies, David2014-07-072014Brownstein, C. A., A. H. Beggs, N. Homer, B. Merriman, T. W. Yu, K. C. Flannery, E. T. DeChene, et al. 2014. “An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.” Genome Biology 15 (3): R53. doi:10.1186/gb-2014-15-3-r53. http://dx.doi.org/10.1186/gb-2014-15-3-r53.1465-6906http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406753Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.en-USAn international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY ChallengeJournal Article2014-07-0710.1186/gb-2014-15-3-r53