title: An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.
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.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brownstein
authors.forename: Alan H
authors.initials: AH
authors.lastname: Beggs
authors.forename: Nils
authors.initials: N
authors.lastname: Homer
authors.forename: Barry
authors.initials: B
authors.lastname: Merriman
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Yu
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Flannery
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: DeChene
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Towne
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Savage
authors.forename: Emily N
authors.initials: EN
authors.lastname: Price
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Holm
authors.forename: Lovelace J
authors.initials: LJ
authors.lastname: Luquette
authors.forename: Elaine
authors.initials: E
authors.lastname: Lyon
authors.forename: Joseph
authors.initials: J
authors.lastname: Majzoub
authors.forename: Peter
authors.initials: P
authors.lastname: Neupert
authors.forename: David
authors.initials: D
authors.lastname: McCallie
authors.forename: Peter
authors.initials: P
authors.lastname: Szolovits
authors.forename: Huntington F
authors.initials: HF
authors.lastname: Willard
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Mendelsohn
authors.forename: Renee
authors.initials: R
authors.lastname: Temme
authors.forename: Richard S
authors.initials: RS
authors.lastname: Finkel
authors.forename: Sabrina W
authors.initials: SW
authors.lastname: Yum
authors.forename: Livija
authors.initials: L
authors.lastname: Medne
authors.forename: Shamil R
authors.initials: SR
authors.lastname: Sunyaev
authors.forename: Ivan
authors.initials: I
authors.lastname: Adzhubey
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Cassa
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Hatice
authors.initials: H
authors.lastname: Duzkale
authors.forename: Piotr
authors.initials: P
authors.lastname: Dworzyński
authors.forename: William
authors.initials: W
authors.lastname: Fairbrother
authors.forename: Laurent
authors.initials: L
authors.lastname: Francioli
authors.forename: Birgit H
authors.initials: BH
authors.lastname: Funke
authors.forename: Monica A
authors.initials: MA
authors.lastname: Giovanni
authors.forename: Robert E
authors.initials: RE
authors.lastname: Handsaker
authors.forename: Kasper
authors.initials: K
authors.lastname: Lage
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Lebo
authors.forename: Monkol
authors.initials: M
authors.lastname: Lek
authors.forename: Ignaty
authors.initials: I
authors.lastname: Leshchiner
authors.forename: Daniel G
authors.initials: DG
authors.lastname: MacArthur
authors.forename: Heather M
authors.initials: HM
authors.lastname: McLaughlin
authors.forename: Michael F
authors.initials: MF
authors.lastname: Murray
authors.forename: Tune H
authors.initials: TH
authors.lastname: Pers
authors.forename: Paz P
authors.initials: PP
authors.lastname: Polak
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rehm
authors.forename: Rachel
authors.initials: R
authors.lastname: Soemedi
authors.forename: Nathan O
authors.initials: NO
authors.lastname: Stitziel
authors.forename: Sara
authors.initials: S
authors.lastname: Vestecka
authors.forename: Jochen
authors.initials: J
authors.lastname: Supper
authors.forename: Claudia
authors.initials: C
authors.lastname: Gugenmus
authors.forename: Bernward
authors.initials: B
authors.lastname: Klocke
authors.forename: Alexander
authors.initials: A
authors.lastname: Hahn
authors.forename: Max
authors.initials: M
authors.lastname: Schubach
authors.forename: Mortiz
authors.initials: M
authors.lastname: Menzel
authors.forename: Saskia
authors.initials: S
authors.lastname: Biskup
authors.forename: Peter
authors.initials: P
authors.lastname: Freisinger
authors.forename: Mario
authors.initials: M
authors.lastname: Deng
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: Janeen L
authors.initials: JL
authors.lastname: Andorf
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Kelli
authors.initials: K
authors.lastname: Ryckman
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Thomas
authors.initials: T
authors.lastname: Bair
authors.forename: E Ann
authors.initials: EA
authors.lastname: Black-Ziegelbein
authors.forename: Terry A
authors.initials: TA
authors.lastname: Braun
authors.forename: Benjamin
authors.initials: B
authors.lastname: Darbro
authors.forename: Adam P
authors.initials: AP
authors.lastname: DeLuca
authors.forename: Diana L
authors.initials: DL
authors.lastname: Kolbe
authors.forename: Todd E
authors.initials: TE
authors.lastname: Scheetz
authors.forename: Aiden E
authors.initials: AE
authors.lastname: Shearer
authors.forename: Rama
authors.initials: R
authors.lastname: Sompallae
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Bassuk
authors.forename: Erik
authors.initials: E
authors.lastname: Edens
authors.forename: Katherine
authors.initials: K
authors.lastname: Mathews
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Shchelochkov
authors.forename: Pamela
authors.initials: P
authors.lastname: Trapane
authors.forename: Aaron
authors.initials: A
authors.lastname: Bossler
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Campbell
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Heusel
authors.forename: Anne
authors.initials: A
authors.lastname: Kwitek
authors.forename: Tara
authors.initials: T
authors.lastname: Maga
authors.forename: Karin
authors.initials: K
authors.lastname: Panzer
authors.forename: Thomas
authors.initials: T
authors.lastname: Wassink
authors.forename: Douglas
authors.initials: D
authors.lastname: Van Daele
authors.forename: Hela
authors.initials: H
authors.lastname: Azaiez
authors.forename: Kevin
authors.initials: K
authors.lastname: Booth
authors.forename: Nic
authors.initials: N
authors.lastname: Meyer
authors.forename: Michael M
authors.initials: MM
authors.lastname: Segal
authors.forename: Marc S
authors.initials: MS
authors.lastname: Williams
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.forename: Peter
authors.initials: P
authors.lastname: White
authors.forename: Donald
authors.initials: D
authors.lastname: Corsmeier
authors.forename: Sara
authors.initials: S
authors.lastname: Fitzgerald-Butt
authors.forename: Gail
authors.initials: G
authors.lastname: Herman
authors.forename: Devon
authors.initials: D
authors.lastname: Lamb-Thrush
authors.forename: Kim L
authors.initials: KL
authors.lastname: McBride
authors.forename: David
authors.initials: D
authors.lastname: Newsom
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Pierson
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Rakowsky
authors.forename: Aleš
authors.initials: A
authors.lastname: Maver
authors.forename: Luca
authors.initials: L
authors.lastname: Lovrečić
authors.forename: Anja
authors.initials: A
authors.lastname: Palandačić
authors.forename: Borut
authors.initials: B
authors.lastname: Peterlin
authors.forename: Ali
authors.initials: A
authors.lastname: Torkamani
authors.forename: Anna
authors.initials: A
authors.lastname: Wedell
authors.forename: Mikael
authors.initials: M
authors.lastname: Huss
authors.forename: Andrey
authors.initials: A
authors.lastname: Alexeyenko
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Lindvall
authors.forename: Måns
authors.initials: M
authors.lastname: Magnusson
authors.forename: Daniel
authors.initials: D
authors.lastname: Nilsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Stranneheim
authors.forename: Fulya
authors.initials: F
authors.lastname: Taylan
authors.forename: Christian
authors.initials: C
authors.lastname: Gilissen
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoischen
authors.forename: Bregje
authors.initials: B
authors.lastname: van Bon
authors.forename: Helger
authors.initials: H
authors.lastname: Yntema
authors.forename: Marcel
authors.initials: M
authors.lastname: Nelen
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.forename: Jason
authors.initials: J
authors.lastname: Sager
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Kathryn
authors.initials: K
authors.lastname: Blair
authors.forename: Deniz
authors.initials: D
authors.lastname: Kural
authors.forename: Michael
authors.initials: M
authors.lastname: Cariaso
authors.forename: Greg G
authors.initials: GG
authors.lastname: Lennon
authors.forename: Asif
authors.initials: A
authors.lastname: Javed
authors.forename: Saloni
authors.initials: S
authors.lastname: Agrawal
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ng
authors.forename: Komal S
authors.initials: KS
authors.lastname: Sandhu
authors.forename: Shuba
authors.initials: S
authors.lastname: Krishna
authors.forename: Vamsi
authors.initials: V
authors.lastname: Veeramachaneni
authors.forename: Ofer
authors.initials: O
authors.lastname: Isakov
authors.forename: Eran
authors.initials: E
authors.lastname: Halperin
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.forename: Gustavo
authors.initials: G
authors.lastname: Glusman
authors.forename: Jared C
authors.initials: JC
authors.lastname: Roach
authors.forename: Juan
authors.initials: J
authors.lastname: Caballero
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Cox
authors.forename: Denise
authors.initials: D
authors.lastname: Mauldin
authors.forename: Seth A
authors.initials: SA
authors.lastname: Ament
authors.forename: Lee
authors.initials: L
authors.lastname: Rowen
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Richards
authors.forename: F Anthony
authors.initials: FA
authors.lastname: San Lucas
authors.forename: Manuel L
authors.initials: ML
authors.lastname: Gonzalez-Garay
authors.forename: C Thomas
authors.initials: CT
authors.lastname: Caskey
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Wang
authors.forename: Jorge
authors.initials: J
authors.lastname: Barrera
authors.forename: Juan M
authors.initials: JM
authors.lastname: Garcia-Lobo
authors.forename: Domingo
authors.initials: D
authors.lastname: González-Lamuño
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Maria C
authors.initials: MC
authors.lastname: Rodriguez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Varela
authors.forename: Martin G
authors.initials: MG
authors.lastname: Reese
authors.forename: Francisco M
authors.initials: FM
authors.lastname: De La Vega
authors.forename: Edward
authors.initials: E
authors.lastname: Kiruluta
authors.forename: Michele
authors.initials: M
authors.lastname: Cargill
authors.forename: Reece K
authors.initials: RK
authors.lastname: Hart
authors.forename: Jon M
authors.initials: JM
authors.lastname: Sorenson
authors.forename: Gholson J
authors.initials: GJ
authors.lastname: Lyon
authors.forename: David A
authors.initials: DA
authors.lastname: Stevenson
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Bray
authors.forename: Barry M
authors.initials: BM
authors.lastname: Moore
authors.forename: Karen
authors.initials: K
authors.lastname: Eilbeck
authors.forename: Mark
authors.initials: M
authors.lastname: Yandell
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.forename: Xiting
authors.initials: X
authors.lastname: Yan
authors.forename: Mengjie
authors.initials: M
authors.lastname: Chen
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Can
authors.initials: C
authors.lastname: Yang
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
authors.forename: Peining
authors.initials: P
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Kong
authors.forename: Austin C
authors.initials: AC
authors.lastname: Alexander
authors.forename: Zayed I
authors.initials: ZI
authors.lastname: Albertyn
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Bulman
authors.forename: Paul M K
authors.initials: PM
authors.lastname: Gordon
authors.forename: A Micheil
authors.initials: AM
authors.lastname: Innes
authors.forename: Bartha M
authors.initials: BM
authors.lastname: Knoppers
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.forename: Jillian S
authors.initials: JS
authors.lastname: Parboosingh
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Sawyer
authors.forename: Mark E
authors.initials: ME
authors.lastname: Samuels
authors.forename: Jeremy
authors.initials: J
authors.lastname: Schwartzentruber
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
authors.forename: David M
authors.initials: DM
authors.lastname: Margulies
mesh_terms: D002648:Child; D030541:Databases, Genetic / Q000592:standards*; D005260:Female; D005381:Financing, Organized; D005820:Genetic Testing / Q000191:economics / Q000379:methods* / Q000592:standards; D023281:Genomics / Q000191:economics / Q000379:methods* / Q000592:standards; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008297:Male; D020914:Myopathies, Structural, Congenital / Q000175:diagnosis / Q000235:genetics; D017712:Peer Review, Research; D017422:Sequence Analysis, DNA / Q000191:economics / Q000379:methods* / Q000592:standards