PT  - JOURNAL ARTICLE
AU  - Nathan D. Olson
AU  - Justin Wagner
AU  - Jennifer McDaniel
AU  - Sarah H. Stephens
AU  - Samuel T. Westreich
AU  - Anish G. Prasanna
AU  - Elaine Johanson
AU  - Emily Boja
AU  - Ezekiel J. Maier
AU  - Omar Serang
AU  - David Jáspez
AU  - José M. Lorenzo-Salazar
AU  - Adrián Muñoz-Barrera
AU  - Luis A. Rubio-Rodríguez
AU  - Carlos Flores
AU  - Konstantinos Kyriakidis
AU  - Andigoni Malousi
AU  - Kishwar Shafin
AU  - Trevor Pesout
AU  - Miten Jain
AU  - Benedict Paten
AU  - Pi-Chuan Chang
AU  - Alexey Kolesnikov
AU  - Maria Nattestad
AU  - Gunjan Baid
AU  - Sidharth Goel
AU  - Howard Yang
AU  - Andrew Carroll
AU  - Robert Eveleigh
AU  - Mathieu Bourgey
AU  - Guillaume Bourque
AU  - Gen Li
AU  - MA ChouXian
AU  - LinQi Tang
AU  - DU YuanPing
AU  - ShaoWei Zhang
AU  - Jordi Morata
AU  - Raúl Tonda
AU  - Genís Parra
AU  - Jean-Rémi Trotta
AU  - Christian Brueffer
AU  - Sinem Demirkaya-Budak
AU  - Duygu Kabakci-Zorlu
AU  - Deniz Turgut
AU  - Özem Kalay
AU  - Gungor Budak
AU  - Kübra Narcı
AU  - Elif Arslan
AU  - Richard Brown
AU  - Ivan J Johnson
AU  - Alexey Dolgoborodov
AU  - Vladimir Semenyuk
AU  - Amit Jain
AU  - H. Serhat Tetikol
AU  - Varun Jain
AU  - Mike Ruehle
AU  - Bryan Lajoie
AU  - Cooper Roddey
AU  - Severine Catreux
AU  - Rami Mehio
AU  - Umair Ahsan
AU  - Qian Liu
AU  - Kai Wang
AU  - Sayed Mohammad Ebrahim Sahraeian
AU  - Li Tai Fang
AU  - Marghoob Mohiyuddin
AU  - Calvin Hung
AU  - Chirag Jain
AU  - Hanying Feng
AU  - Zhipan Li
AU  - Luoqi Chen
AU  - Fritz J. Sedlazeck
AU  - Justin M. Zook
TI  - precisionFDA Truth Challenge V2: Calling variants from short- and long-reads in difficult-to-map regions
AID  - 10.1101/2020.11.13.380741
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.13.380741
4099  - http://biorxiv.org/content/early/2020/11/19/2020.11.13.380741.short
4100  - http://biorxiv.org/content/early/2020/11/19/2020.11.13.380741.full
AB  - The precisionFDA Truth Challenge V2 aimed to assess the state-of-the-art of variant calling in difficult-to-map regions and the Major Histocompatibility Complex (MHC). Starting with FASTQ files, 20 challenge participants applied their variant calling pipelines and submitted 64 variant callsets for one or more sequencing technologies (~35X Illumina, ~35X PacBio HiFi, and ~50X Oxford Nanopore Technologies). Submissions were evaluated following best practices for benchmarking small variants with the new GIAB benchmark sets and genome stratifications. Challenge submissions included a number of innovative methods for all three technologies, with graph-based and machine-learning methods scoring best for short-read and long-read datasets, respectively. New methods out-performed the 2016 Truth Challenge winners, and new machine-learning approaches combining multiple sequencing technologies performed particularly well. Recent developments in sequencing and variant calling have enabled benchmarking variants in challenging genomic regions, paving the way for the identification of previously unknown clinically relevant variants.Competing Interest StatementC.B. is an employee and shareholder of SAGA Diagnostics AB. A.C., P.C., A.K., M.N., G.B., S.G., and H.Y. are employees of Google and A.C. is a shareholder. S.D., D.K., D.T., O.K., G.B., K.N., E.A., R.B., I.J.J., A.D., V.S., A.J., and H.S.T. are employees of Seven Bridges Genomics. O.S. and S.T.W. are employees of DNAnexus. G.L, C.M, L.T., Y.D., and S.Z. are employees of Genetalks. V.J., M.R., B.L., C.R, S.C., and R.M are employees of Illumina. S.M.E.S., and M.M. are employees of Roche. C.H. is an employee of Wasai Technology. H.F., Z.L, and L.C. are employees of Sentieon Inc.