RT Journal Article
SR Electronic
T1 Reference-based phasing using the Haplotype Reference Consortium panel
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 052308
DO 10.1101/052308
A1 Po-Ru Loh
A1 Petr Danecek
A1 Pier Francesco Palamara
A1 Christian Fuchsberger
A1 Yakir A Reshef
A1 Hilary K Finucane
A1 Sebastian Schoenherr
A1 Lukas Forer
A1 Shane McCarthy
A1 Goncalo R Abecasis
A1 Richard Durbin
A1 Alkes L Price
YR 2016
UL http://biorxiv.org/content/early/2016/07/07/052308.abstract
AB Haplotype phasing is a fundamental problem in medical and population genetics. Phasing is generally performed via statistical phasing within a genotyped cohort, an approach that can attain high accuracy in very large cohorts but attains lower accuracy in smaller cohorts. Here, we instead explore the paradigm of reference-based phasing. We introduce a new phasing algorithm, Eagle2, that attains high accuracy across a broad range of cohort sizes by efficiently leveraging information from large external reference panels (such as the Haplotype Reference Consortium, HRC) using a new data structure based on the positional BurrowsWheeler transform. We demonstrate that Eagle2 attains a ≈20x speedup and ≈10% increase in accuracy compared to reference-based phasing using SHAPEIT2. On European-ancestry samples, Eagle2 with the HRC panel achieves >2x the accuracy of 1000 Genomes-based phasing. Eagle2 is open source and freely available for HRC-based phasing via the Sanger Imputation Service and the Michigan Imputation Server.