Summary
Genome in a Bottle (GIAB) benchmarks have been widely used to help validate clinical sequencing pipelines and develop new variant calling and sequencing methods. Here, we use accurate linked reads and long reads to expand the prior benchmarks in 7 samples to include difficult-to-map regions and segmental duplications that are not readily accessible to short reads. Our new benchmark adds more than 300,000 SNVs, 50,000 indels, and 16 % new exonic variants, many in challenging, clinically relevant genes not previously covered (e.g., PMS2). For HG002, we include 92% of the autosomal GRCh38 assembly, while excluding problematic regions for benchmarking small variants (e.g., copy number variants and reference errors) that should not have been in the previous version, which included 85% of GRCh38. By including difficult-to-map regions, this benchmark identifies eight times more false negatives in a short read variant call set relative to our previous benchmark.We have demonstrated the utility of this benchmark to reliably identify false positives and false negatives across technologies in more challenging regions, which enables continued technology and bioinformatics development.
Competing Interest Statement
AMW and WJR are employees and shareholders of Pacific Biosciences. AMB and ITF were employees and shareholders of 10X Genomics. FJS has received sponsored travel from Oxford Nanopore and Pacific Biosciences, and received a 2018 sequencing grant from Pacific Biosciences. AS and VK are employees of Seven Bridges. AC is an employee of Google Inc. and is a former employee of DNAnexus. AF and C-SC are employees of DNAnexus. SMES is an employee of Roche.
Footnotes
↵# The work was jointly supervised by these authors
fix author list
https://ftp-trace.ncbi.nlm.nih.gov/ReferenceSamples/giab/release/