Abstract 3636: Improved clinical variant calling and HLA genotyping with GRCh38

Abstract

Abstract The Genome Reference Consortium released human genome build 38 (hg38, GRCh38) two years ago and it offers major improvements over the six year old previous build, 37 (hg19, GRCh37). The new build reflects our increased understanding of the heterogeneity within human sub-populations, contains a large number of alternative genomic loci that better capture our knowledge of genome structure, and includes highly diverse human leukocyte antigen (HLA) regions enabling HLA typing. To help with the migration of clinical sequencing workflows we provide support for variant calling on build 38, validate methods using truth sets from the Genome in a Bottle consortium and Illumina's Platinum Genome and show that feature projection approaches are a viable intermediate approach to port existing annotation resources. We show how the refined genomic representation improves mapping and variant calling by reducing the number of false positive SNP calls and improving InDel detection, and how post-processing of sequence reads mapping to HLA regions enables accurate HLA genotyping from targeted panels, exome- and WGS data. Using Omixon HLA validation data, integrated OptiType HLA calling achieved 100% accuracy on 8 targeted panels and better than 90% accuracy on 1000 genome exome samples. This work provides a freely available, validated, ready to run pipeline making use of the improved heterogeneity representation in build 38 and demonstrating the value of moving towards a more accurate, graph-based representation of human genomes. Citation Format: Brad Chapman, Alison Meynert, Deanna Church, Justin Johnson, Oliver Hofmann. Improved clinical variant calling and HLA genotyping with GRCh38. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3636.