A complete diploid human genome benchmark for personalized genomics
TL;DR
A telomere-to-telomere genome benchmark with near-perfect accuracy across 99.4% of the diploid HG002 genome is presented, expanding the reach of genomic medicine to the entire genome and enabling a new era of personalized genomics.
Abstract
SUMMARY Human genome sequencing typically relies on mapping reads to a reference genome to call variants, but this approach introduces technical biases, excluding duplicated and structurally polymorphic regions of the genome. To overcome this, we present a telomere-to-telomere genome benchmark with near-perfect accuracy across 99.4% of the diploid HG002 genome. This benchmark adds 701.4 Mb of autosomal sequence and both sex chromosomes (216.8 Mb), which were absent from prior benchmarks. We annotated genes and repeats on both haplotypes, including 19,956 protein-coding genes on the maternal haplotype and 19,190 on the paternal haplotype, and developed new methods to measure the accuracy of reads, phased variant call sets, and assemblies against a diploid reference. Genome-wide analyses show that de novo assembly resolves 2%–7% more sequence and outperforms variant calling accuracy by an order of magnitude, expanding the reach of genomic medicine to the entire genome and enabling a new era of personalized genomics.