Abstract
AbstractVariant discovery in personal, whole genome sequence data is critical for uncovering the genetic contributions to health and disease. We introduce a new approach, Aquila, that uses linked-read data for generating a high quality diploid genome assembly, from which it then comprehensively detects and phases personal genetic variation. Assemblies cover >95% of the human reference genome, with over 98% in a diploid state. Thus, the assemblies support detection and accurate genotyping of the most prevalent types of human genetic variation, including single nucleotide polymorphisms (SNPs), small insertions and deletions (small indels), and structural variants (SVs), in all but the most difficult regions. All heterozygous variants are phased in blocks that can approach arm-level length. The final output of Aquila is a diploid and phased personal genome sequence, and a phased VCF file that also contains homozygous and a few unphased heterozygous variants. Aquila represents a cost-effective evolution of whole-genome reconstruction that can be applied to cohorts for variation discovery or association studies, or to single individuals with rare phenotypes that could be caused by SVs or compound heterozygosity.
Publisher
Cold Spring Harbor Laboratory
Reference35 articles.
1. Characterizing the Major Structural Variant Alleles of the Human Genome;Cell,2019
2. SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing
3. Multi-platform discovery of haplotype-resolved structural variation in human genomes
4. Chin C-S , Peluso P , Sedlazeck FJ , Nattestad M , Concepcion GT , Clum A , Dunn C , O’malley R , Figueroa-Balderas R , Morales-Cruz A , et al. 2016. Phased diploid genome assembly with single-molecule real-time sequencing. Articles 1050.
5. Coster W De , Roeck A De , Pooter T De , D’Hert S , Rijk P De , Strazisar M , Sleegers K , Broeckhoven C Van . 2018. Structural variants identified by Oxford Nanopore PromethION sequencing of the human genome. bioRxiv 434118.
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献