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

Citation:

Brownstein CA, Beggs AH, Homer N, Merriman B, Yu TW, Flannery KC, DeChene ET, Towne MC, Savage SK, Price EN, et al. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge. Genome BiolGenome Biol. 2014;15 :R53.

Abstract:

BACKGROUND: 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.

Notes:

Brownstein, Catherine ABeggs, Alan HHomer, NilsMerriman, BarryYu, Timothy WFlannery, Katherine CDeChene, Elizabeth TTowne, Meghan CSavage, Sarah KPrice, Emily NHolm, Ingrid ALuquette, Lovelace JLyon, ElaineMajzoub, JosephNeupert, PeterMcCallie, David JrSzolovits, PeterWillard, Huntington FMendelsohn, Nancy JTemme, ReneeFinkel, Richard SYum, Sabrina WMedne, LivijaSunyaev, Shamil RAdzhubey, IvanCassa, Christopher Ade Bakker, Paul I WDuzkale, HaticeDworzynski, PiotrFairbrother, WilliamFrancioli, LaurentFunke, Birgit HGiovanni, Monica AHandsaker, Robert ELage, KasperLebo, Matthew SLek, MonkolLeshchiner, IgnatyMacArthur, Daniel GMcLaughlin, Heather MMurray, Michael FPers, Tune HPolak, Paz PRaychaudhuri, SoumyaRehm, Heidi LSoemedi, RachelStitziel, Nathan OVestecka, SaraSupper, JochenGugenmus, ClaudiaKlocke, BernwardHahn, AlexanderSchubach, MaxMenzel, MortizBiskup, SaskiaFreisinger, PeterDeng, MarioBraun, MartinPerner, SvenSmith, Richard J HAndorf, 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, AlesLovrecic, LucaPalandacic, AnjaPeterlin, BorutTorkamani, AliWedell, AnnaHuss, MikaelAlexeyenko, AndreyLindvall, Jessica MMagnusson, MansNilsson, 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 RSan Lucas, F AnthonyGonzalez-Garay, Manuel LCaskey, C ThomasBai, YuHuang, YingFang, FangZhang, YanWang, ZhengyuanBarrera, JorgeGarcia-Lobo, Juan MGonzalez-Lamuno, 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 M KInnes, A MicheilKnoppers, Bartha MMajewski, JacekMarshall, Christian RParboosingh, Jillian SSawyer, Sarah LSamuels, Mark ESchwartzentruber, JeremyKohane, Isaac SMargulies, David MengK99 HG007229/HG/NHGRI NIH HHS/R01 HL109758/HL/NHLBI NIH HHS/Howard Hughes Medical Institute/Research Support, Non-U.S. Gov'tEngland2014/03/29 06:00Genome Biol. 2014 Mar 25;15(3):R53. doi: 10.1186/gb-2014-15-3-r53.