Laboratory Practice

Select publications that evaluate technical aspects of WGS, including analytical validity, quality metrics and best practices
Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study.
Ibanez K, Polke J, Hagelstrom RT, et al. Neurol. 2022 Mar;21(3):234-245. doi: 10.1016/S1474-4422(21)00462-2


A randomized controlled trial of the analytic and diagnostic performance of singleton and trio, rapid genome and exome sequencing in ill infants.
Kingsmore SF, Cakici JA, Clark MM, Gaughran M, Feddock M, Batalov S, Bainbridge MN, Carroll J, Caylor SA, Clarke C, Ding Y, ellsworth K, Farnaes L, Hildreth A, Hobbs C, James K, King CI, Lenberg J, NahasS, Prince L, Reyes I, Salz L, Sanford E, Schols P, Sweeney N, Tokita M, Veeraraghavan N, Watkins K, Wigby K, Wong T, Chowdhury S, Wright MS, Dimmock D, RCIGM Investigators.  A J Hum Gen, 2019;105:1-15.

NSIGHT2 is a prospective, randomized-controlled trial comparing rapid whole genome sequencing (WGS) and rapid whole exome sequencing (WES) to infants <4 months of age within 96 hours of NICU/PICU admission or onset of features. Singleton analysis was performed for all samples with secondary trio reanalysis performed as reflex to negative results. Gravely ill infants underwent trio, ultra-rapid WGS. The combined diagnostic yield in this study was 23%. Yield was not significantly different between rapid WGS (20%) and rapid WES (19%); however, it was higher (24%) in ultra-rapid WGS. Median time to diagnosis was similar between rWGS and rWES (11.0 d vs. 11.2 d). urWGS and rWGS combined identified two times more pathogenic and likely pathogenic variants than WES. The authors conclude that the analytical performance of rWGS is superior to rWES supporting the use of rWGS as a first-tier test in the NICU/PICU setting.

A Rigorous Interlaboratory Examination of the Need to Confirm Next-Generation Sequencing-Detected Variants with an Orthogonal Method in Clinical Genetic Testing.
Lincoln SE, Truty R, Lin CF, Zook JM, Paul J, Ramey VH, Salit M, Rehm HL, Nussbaum RL, Lebo MS.  J Mol Diagn. 2019 Mar;21(2):318-329. doi: 10.1016/j.jmoldx.2018.10.009.


Good laboratory practice for clinical next-generation sequencing informatics pipelines
Gargis AS, Kalman L, Bick DP, da Silva C, Dimmock DP, Funke BH, Gowrisankar S, Hedge MR, Kulkarni S, Mason CE, Nagarajan R, Voelkerding KV, Worthey EA, Aziz N, Barnes J, Bennett SF, Bisht H, Church DM, Dimitrova Z, Gargis SR, Hafez N, Hambuch T, Hyland FCL, Luna RA, MacCannell D, Mann T, McCluskey MR, McDaniel TK, Ganova-Raeva LM, Rehm HL, Reid J, Campo DS, Resnick RB, Ridge PG, Salit ML, Skums P, Wong LJC, Zehnbauer BA, Lubin IM.  Nat Biotechnol. 2015;33(7):689–693. doi:10.1038/nbt.3237.


Rapid Paediatric Sequencing (RaPS): comprehensive real-life workflow for rapid diagnosis of critically ill children.
Mestek-Boukhibar l, Clement E, Jones WD, Drury S, Ocaka L, Gagunashvili A, Le Quesne Stabej P, Bacchelli C, Jani N, Rahman S, Jenkins L, Hurst JA, Bitner-Glindzicz M, Peters M, Beales PL, Williams HJ. J Med Genet. 2018; 55:721–728.


A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories
O’Daniel JM, McLaughlin HM, Amendola LM, Bale SJ, Berg JB, Bick D, Bowling KM, Chao EC, Chung WK, Conlin LK, Cooper GM, Das S, Deignan JL, Dorschner MO, Evans JP, Ghazani AA, Goddard KA, Gornick M, Farwell Hagman KD, Hambuch T, Hedge M, Hindorff LA, Holm IA, Jarvik GP, Knight Johnson A, Mighion L, Morra M, Plon SE, Punj S, Richards CS, Santani A, Shirts BH, Spinner NB, Tang S, Weck KE, Wolf SM, Yang Y, Rehm HL. Genet Med. 2016;19(5):575–582. doi:10.1038/gim.2016.152.


An open resource for accurately benchmarking small variant and reference calls.
Zook JM, McDaniel J, Olson ND, Wagner J, Parikh H, Heaton H, Irvine SA, Trigg L, Truty R, McLean CY, De La Vega FM, Xiao C, Sherry S, Salit M. Nat Biotechnol. 2019;37(5):561-566.


Genomic medicine for undiagnosed diseases
Wise AL, Manolio TA, Mesah GA, Peterson JF, Roden DM, Tamburro C, Williams MS, Green ED.. Lancet, 2019; 394: 533-40.


Best practices for benchmarking germline small-variant calls in human genomes.
Krusche P, Trigg L, Boutros PC, Mason CE, De La Vega FM, Moore BL, Gonzalez-Porta M, Eberle MA, Tezak Z, Lababidi S, Truty R, Asimenos G, Funke B, Fleharty M, Chapman BA, Salit M, Zook JM, Global Alliance for Genomics and Health Benchmarking Team.  Nat Biotechnol. 2019 May;37(5):555-560. doi: 10.1038/s41587-019-0054-x.

Recommendations for next generation sequencing data reanalysis of unsolved cases with suspected Mendelian disorders: A systematic review and meta-analysis. Dai P, Honda A, Ewans L, et al. Genet. Med. 2022

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