@article{2097fc7fd0734b66bb71fecfbf9b5e6c,
title = "Standard operating procedure for somatic variant refinement of sequencing data with paired tumor and normal samples",
abstract = "Purpose: Following automated variant calling, manual review of aligned read sequences is required to identify a high-quality list of somatic variants. Despite widespread use in analyzing sequence data, methods to standardize manual review have not been described, resulting in high inter- and intralab variability. Methods: This manual review standard operating procedure (SOP) consists of methods to annotate variants with four different calls and 19 tags. The calls indicate a reviewer{\textquoteright}s confidence in each variant and the tags indicate commonly observed sequencing patterns and artifacts that inform the manual review call. Four individuals were asked to classify variants prior to, and after, reading the SOP and accuracy was assessed by comparing reviewer calls with orthogonal validation sequencing. Results: After reading the SOP, average accuracy in somatic variant identification increased by 16.7% (p value = 0.0298) and average interreviewer agreement increased by 12.7% (p value < 0.001). Manual review conducted after reading the SOP did not significantly increase reviewer time. Conclusion: This SOP supports and enhances manual somatic variant detection by improving reviewer accuracy while reducing the interreviewer variability for variant calling and annotation.",
keywords = "manual review, somatic variant refinement",
author = "Barnell, {Erica K.} and Peter Ronning and Campbell, {Katie M.} and Kilannin Krysiak and Ainscough, {Benjamin J.} and Sheta, {Lana M.} and Pema, {Shahil P.} and Schmidt, {Alina D.} and Megan Richters and Cotto, {Kelsy C.} and Danos, {Arpad M.} and Cody Ramirez and Skidmore, {Zachary L.} and Spies, {Nicholas C.} and Jasreet Hundal and Sediqzad, {Malik S.} and Jason Kunisaki and Felicia Gomez and Lee Trani and Matthew Matlock and Wagner, {Alex H.} and Swamidass, {S. Joshua} and Malachi Griffith and Griffith, {Obi L.}",
note = "Funding Information: E.K.B. was supported by the National Cancer Institute (T32GM007200 and U01CA209936). B.J.A. and K.M.C. were supported by the Siteman Cancer Center (T32CA113275). S.J.S. is funded by the National Library of Medicine (NIH NLM R01LM012222 and NIH NLM R01LM012482). A.W. was supported by the National Cancer Institute (NIH NCI F32CA206247). M.G. is funded by the National Human Genome Research Institute (NIH NHGRI R00HG007940). O.L.G. is funded by the National Cancer Institute (NIH NCI K22CA188163 and NIH NCI U01CA209936). Additional funds were provided by the Washington University School of Medicine. This research would not have been possible without exemplary work performed by Michael McLellan, Heather Schmidt, Jennifer Hodges, Yat Tang, Li Ding, and others at the McDonnell Genome Institute to develop the original Medical Genomics/Manual Review Guidelines. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2019",
month = apr,
day = "1",
doi = "10.1038/s41436-018-0278-z",
language = "English",
volume = "21",
pages = "972--981",
journal = "Genetics in Medicine",
issn = "1098-3600",
number = "4",
}