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

Catherine A. Brownstein, Alan H. Beggs, Nils Homer, Barry Merriman, Timothy W. Yu, Katherine C. Flannery, Elizabeth T. DeChene, Meghan C. Towne, Sarah K. Savage, Emily N. Price, Ingrid A. Holm, Lovelace J. Luquette, Elaine Lyon, Joseph Majzoub, Peter Neupert, David McCallie, Peter Szolovits, Huntington F. Willard, Nancy J. Mendelsohn, Renee TemmeRichard S. Finkel, Sabrina W. Yum, Livija Medne, Shamil R. Sunyaev, Ivan Adzhubey, Christopher A. Cassa, Paul I.W. De Bakker, Hatice Duzkale, Piotr Dworzyński, William Fairbrother, Laurent Francioli, Birgit H. Funke, Monica A. Giovanni, Robert E. Handsaker, Kasper Lage, Matthew S. Lebo, Monkol Lek, Ignaty Leshchiner, Daniel G. MacArthur, Heather M. McLaughlin, Michael F. Murray, Tune H. Pers, Paz P. Polak, Soumya Raychaudhuri, Heidi L. Rehm, Rachel Soemedi, Nathan O. Stitziel, Sara Vestecka, Jochen Supper, Claudia Gugenmus, Bernward Klocke, Alexander Hahn, Max Schubach, Mortiz Menzel, Saskia Biskup, Peter Freisinger, Mario Deng, Martin Braun, Sven Perner, Richard J.H. Smith, Janeen L. Andorf, Jian Huang, Kelli Ryckman, Val C. Sheffield, Edwin M. Stone, Thomas Bair, E. Ann Black-Ziegelbein, Terry A. Braun, Benjamin Darbro, Adam P. DeLuca, Diana L. Kolbe, Todd E. Scheetz, Aiden E. Shearer, Rama Sompallae, Kai Wang, Alexander G. Bassuk, Erik Edens, Katherine Mathews, Steven A. Moore, Oleg A. Shchelochkov, Pamela Trapane, Aaron Bossler, Colleen A. Campbell, Jonathan W. Heusel, Anne Kwitek, Tara Maga, Karin Panzer, Thomas Wassink, Douglas Van Daele, Hela Azaiez, Kevin Booth, Nic Meyer, Michael M. Segal, Marc S. Williams

Research output: Journal article publicationJournal articleAcademic researchpeer-review

79 Citations (Scopus)


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.
Original languageEnglish
Article numberR53
JournalGenome Biology
Issue number3
Publication statusPublished - 1 Jan 2014
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

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