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

Authors:
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 Temme Richard 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 Gerard Tromp Peter White Donald Corsmeier Sara Fitzgerald-Butt Gail Herman Devon Lamb-Thrush Kim L McBride David Newsom Christopher R Pierson Alexander T Rakowsky Aleš Maver Luca Lovrečić Anja Palandačić Borut Peterlin Ali Torkamani Anna Wedell Mikael Huss Andrey Alexeyenko Jessica M Lindvall Måns Magnusson Daniel Nilsson Henrik Stranneheim Fulya Taylan Christian Gilissen Alexander Hoischen Bregje van Bon Helger Yntema Marcel Nelen Weidong Zhang Jason Sager Lu Zhang Kathryn Blair Deniz Kural Michael Cariaso Greg G Lennon Asif Javed Saloni Agrawal Pauline C Ng Komal S Sandhu Shuba Krishna Vamsi Veeramachaneni Ofer Isakov Eran Halperin Eitan Friedman Noam Shomron Gustavo Glusman Jared C Roach Juan Caballero Hannah C Cox Denise Mauldin Seth A Ament Lee Rowen Daniel R Richards F Anthony San Lucas Manuel L Gonzalez-Garay C Thomas Caskey Yu Bai Ying Huang Fang Fang Yan Zhang Zhengyuan Wang Jorge Barrera Juan M Garcia-Lobo Domingo González-Lamuño Javier Llorca Maria C Rodriguez Ignacio Varela Martin G Reese Francisco M De La Vega Edward Kiruluta Michele Cargill Reece K Hart Jon M Sorenson Gholson J Lyon David A Stevenson Bruce E Bray Barry M Moore Karen Eilbeck Mark Yandell Hongyu Zhao Lin Hou Xiaowei Chen Xiting Yan Mengjie Chen Cong Li Can Yang Murat Gunel Peining Li Yong Kong Austin C Alexander Zayed I Albertyn Kym M Boycott Dennis E Bulman Paul M K Gordon A Micheil Innes Bartha M Knoppers Jacek Majewski Christian R Marshall Jillian S Parboosingh Sarah L Sawyer Mark E Samuels Jeremy Schwartzentruber Isaac S Kohane David M Margulies

Genome Biol 2014 Mar 25;15(3):R53. Epub 2014 Mar 25.

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.

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Source
http://dx.doi.org/10.1186/gb-2014-15-3-r53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073084PMC
March 2014
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