PT  - JOURNAL ARTICLE
AU  - Olson, Nathan D.
AU  - Wagner, Justin
AU  - McDaniel, Jennifer
AU  - Stephens, Sarah H.
AU  - Westreich, Samuel T.
AU  - Prasanna, Anish G.
AU  - Johanson, Elaine
AU  - Boja, Emily
AU  - Maier, Ezekiel J.
AU  - Serang, Omar
AU  - Jáspez, David
AU  - Lorenzo-Salazar, José M.
AU  - Muñoz-Barrera, Adrián
AU  - Rubio-Rodríguez, Luis A.
AU  - Flores, Carlos
AU  - Kyriakidis, Konstantinos
AU  - Malousi, Andigoni
AU  - Shafin, Kishwar
AU  - Pesout, Trevor
AU  - Jain, Miten
AU  - Paten, Benedict
AU  - Chang, Pi-Chuan
AU  - Kolesnikov, Alexey
AU  - Nattestad, Maria
AU  - Baid, Gunjan
AU  - Goel, Sidharth
AU  - Yang, Howard
AU  - Carroll, Andrew
AU  - Eveleigh, Robert
AU  - Bourgey, Mathieu
AU  - Bourque, Guillaume
AU  - Li, Gen
AU  - ChouXian, MA
AU  - Tang, LinQi
AU  - YuanPing, DU
AU  - Zhang, ShaoWei
AU  - Morata, Jordi
AU  - Tonda, Raúl
AU  - Parra, Genís
AU  - Trotta, Jean-Rémi
AU  - Brueffer, Christian
AU  - Demirkaya-Budak, Sinem
AU  - Kabakci-Zorlu, Duygu
AU  - Turgut, Deniz
AU  - Kalay, Özem
AU  - Budak, Gungor
AU  - Narcı, Kübra
AU  - Arslan, Elif
AU  - Brown, Richard
AU  - Johnson, Ivan J
AU  - Dolgoborodov, Alexey
AU  - Semenyuk, Vladimir
AU  - Jain, Amit
AU  - Tetikol, H. Serhat
AU  - Jain, Varun
AU  - Ruehle, Mike
AU  - Lajoie, Bryan
AU  - Roddey, Cooper
AU  - Catreux, Severine
AU  - Mehio, Rami
AU  - Ahsan, Umair
AU  - Liu, Qian
AU  - Wang, Kai
AU  - Sahraeian, Sayed Mohammad Ebrahim
AU  - Fang, Li Tai
AU  - Mohiyuddin, Marghoob
AU  - Hung, Calvin
AU  - Jain, Chirag
AU  - Feng, Hanying
AU  - Li, Zhipan
AU  - Chen, Luoqi
AU  - Sedlazeck, Fritz J.
AU  - Zook, Justin M.
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.