PURPOSE: Genome-wide sequencing approaches are increasingly being used in place of disease gene panel sequencing approaches. Despite the well-recognized benefits of these approaches, they also carry with them an increased burden of analyzing overwhelmingly large gene targets and an increased possibility of detecting incidental findings. METHODS: We propose a novel approach for design of individualized phenotype gene panels using the set of signs and symptoms observed and selecting relevant genes on the basis of known phenotype-gene associations. RESULTS: We used results of diagnostic exome sequencing in 405 cases submitted to our institution to show retrospectively that using the phenotype gene panel increases the sensitivity of masked exome analysis (increase from 25.4 to 29.7% in overall diagnostic yield). We also show that such a strategy enables the possibility of masked analysis of genome-wide sequencing data in patients with poorly defined and multifaceted clinical presentations. Ultimately, we show that this approach enables control over the incidental findings rate (0.25% in phenotype gene panels). Finally, we provide a Web tool for customized phenotype panel creation (available at http://www.kimg.eu/generator). CONCLUSION: In conclusion, we present a novel approach to a phenotype-driven diagnostic process of genome scale sequencing data that harnesses the sensitivity of these approaches while restricting the analysis to genes relevant to clinical presentation in patient.Genet Med 18 11, 1102-1110.
PURPOSE: Genome-wide sequencing approaches are increasingly being used in place of disease gene panel sequencing approaches. Despite the well-recognized benefits of these approaches, they also carry with them an increased burden of analyzing overwhelmingly large gene targets and an increased possibility of detecting incidental findings. METHODS: We propose a novel approach for design of individualized phenotype gene panels using the set of signs and symptoms observed and selecting relevant genes on the basis of known phenotype-gene associations. RESULTS: We used results of diagnostic exome sequencing in 405 cases submitted to our institution to show retrospectively that using the phenotype gene panel increases the sensitivity of masked exome analysis (increase from 25.4 to 29.7% in overall diagnostic yield). We also show that such a strategy enables the possibility of masked analysis of genome-wide sequencing data in patients with poorly defined and multifaceted clinical presentations. Ultimately, we show that this approach enables control over the incidental findings rate (0.25% in phenotype gene panels). Finally, we provide a Web tool for customized phenotype panel creation (available at http://www.kimg.eu/generator). CONCLUSION: In conclusion, we present a novel approach to a phenotype-driven diagnostic process of genome scale sequencing data that harnesses the sensitivity of these approaches while restricting the analysis to genes relevant to clinical presentation in patient.Genet Med 18 11, 1102-1110.
Authors: Kelly E Ormond; Matthew T Wheeler; Louanne Hudgins; Teri E Klein; Atul J Butte; Russ B Altman; Euan A Ashley; Henry T Greely Journal: Lancet Date: 2010-04-29 Impact factor: 79.321
Authors: Kornelia Neveling; Ilse Feenstra; Christian Gilissen; Lies H Hoefsloot; Erik-Jan Kamsteeg; Arjen R Mensenkamp; Richard J T Rodenburg; Helger G Yntema; Liesbeth Spruijt; Sascha Vermeer; Tuula Rinne; Koen L van Gassen; Danielle Bodmer; Dorien Lugtenberg; Rick de Reuver; Wendy Buijsman; Ronny C Derks; Nienke Wieskamp; Bert van den Heuvel; Marjolijn J L Ligtenberg; Hannie Kremer; David A Koolen; Bart P C van de Warrenburg; Frans P M Cremers; Carlo L M Marcelis; Jan A M Smeitink; Saskia B Wortmann; Wendy A G van Zelst-Stams; Joris A Veltman; Han G Brunner; Hans Scheffer; Marcel R Nelen Journal: Hum Mutat Date: 2013-10-18 Impact factor: 4.878
Authors: Michael O Dorschner; Laura M Amendola; Emily H Turner; Peggy D Robertson; Brian H Shirts; Carlos J Gallego; Robin L Bennett; Kelly L Jones; Mari J Tokita; James T Bennett; Jerry H Kim; Elisabeth A Rosenthal; Daniel S Kim; Holly K Tabor; Michael J Bamshad; Arno G Motulsky; C Ronald Scott; Colin C Pritchard; Tom Walsh; Wylie Burke; Wendy H Raskind; Peter Byers; Fuki M Hisama; Deborah A Nickerson; Gail P Jarvik Journal: Am J Hum Genet Date: 2013-09-19 Impact factor: 11.025
Authors: D G MacArthur; T A Manolio; D P Dimmock; H L Rehm; J Shendure; G R Abecasis; D R Adams; R B Altman; S E Antonarakis; E A Ashley; J C Barrett; L G Biesecker; D F Conrad; G M Cooper; N J Cox; M J Daly; M B Gerstein; D B Goldstein; J N Hirschhorn; S M Leal; L A Pennacchio; J A Stamatoyannopoulos; S R Sunyaev; D Valle; B F Voight; W Winckler; C Gunter Journal: Nature Date: 2014-04-24 Impact factor: 49.962
Authors: Gareth Baynam; Stephanie Broley; Alicia Bauskis; Nicholas Pachter; Fiona McKenzie; Sharron Townshend; Jennie Slee; Cathy Kiraly-Borri; Anand Vasudevan; Anne Hawkins; Lyn Schofield; Petra Helmholz; Richard Palmer; Stefanie Kung; Caroline E Walker; Caron Molster; Barry Lewis; Kym Mina; John Beilby; Gargi Pathak; Cathryn Poulton; Tudor Groza; Andreas Zankl; Tony Roscioli; Marcel E Dinger; John S Mattick; William Gahl; Stephen Groft; Cynthia Tifft; Domenica Taruscio; Paul Lasko; Kenjiro Kosaki; Helene Wilhelm; Bela Melegh; Jonathan Carapetis; Sayanta Jana; Gervase Chaney; Allison Johns; Peter Wynn Owen; Frank Daly; Tarun Weeramanthri; Hugh Dawkins; Jack Goldblatt Journal: Orphanet J Rare Dis Date: 2017-05-03 Impact factor: 4.123
Authors: D Allegrini; S Penco; A Pece; A Autelitano; G Montesano; S Paci; C Montanari; A Maver; B Peterlin; G Damante; L Rossetti Journal: BMC Ophthalmol Date: 2017-06-28 Impact factor: 2.209
Authors: Sebastian Köhler; Nicole A Vasilevsky; Mark Engelstad; Erin Foster; Julie McMurry; Ségolène Aymé; Gareth Baynam; Susan M Bello; Cornelius F Boerkoel; Kym M Boycott; Michael Brudno; Orion J Buske; Patrick F Chinnery; Valentina Cipriani; Laureen E Connell; Hugh J S Dawkins; Laura E DeMare; Andrew D Devereau; Bert B A de Vries; Helen V Firth; Kathleen Freson; Daniel Greene; Ada Hamosh; Ingo Helbig; Courtney Hum; Johanna A Jähn; Roger James; Roland Krause; Stanley J F Laulederkind; Hanns Lochmüller; Gholson J Lyon; Soichi Ogishima; Annie Olry; Willem H Ouwehand; Nikolas Pontikos; Ana Rath; Franz Schaefer; Richard H Scott; Michael Segal; Panagiotis I Sergouniotis; Richard Sever; Cynthia L Smith; Volker Straub; Rachel Thompson; Catherine Turner; Ernest Turro; Marijcke W M Veltman; Tom Vulliamy; Jing Yu; Julie von Ziegenweidt; Andreas Zankl; Stephan Züchner; Tomasz Zemojtel; Julius O B Jacobsen; Tudor Groza; Damian Smedley; Christopher J Mungall; Melissa Haendel; Peter N Robinson Journal: Nucleic Acids Res Date: 2016-11-28 Impact factor: 16.971
Authors: Timo Lassmann; Richard W Francis; Alexia Weeks; Dave Tang; Sarra E Jamieson; Stephanie Broley; Hugh J S Dawkins; Lauren Dreyer; Jack Goldblatt; Tudor Groza; Benjamin Kamien; Cathy Kiraly-Borri; Fiona McKenzie; Lesley Murphy; Nicholas Pachter; Gargi Pathak; Cathryn Poulton; Amanda Samanek; Rachel Skoss; Jennie Slee; Sharron Townshend; Michelle Ward; Gareth S Baynam; Jenefer M Blackwell Journal: NPJ Genom Med Date: 2020-12-10 Impact factor: 8.617