Chromosome-scale, haplotype-resolved assembly of human genomes.
Shilpa GargArkarachai FungtammasanAndrew CarrollMike ChouAnthony SchmittXiang ZhouStephen MacPaul PelusoEmily HatasJay GhuryeJared MaguireMedhat MahmoudHaoyu ChengDavid HellerJustin M ZookTobias MoemkeTobias MarschallFritz J SedlazeckJohn AachChen-Shan ChinGeorge M ChurchHeng LiPublished in: Nature biotechnology (2020)
Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1 day. Applied to four public human genomes, PGP1, HG002, NA12878 and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig length needed to cover 50% of the known genome (NG50) up to 25 Mb and phased ~99.5% of heterozygous sites at 98-99% accuracy, outperforming other approaches in terms of both contiguity and phasing completeness. We demonstrate the importance of chromosome-scale phased assemblies for the discovery of structural variants (SVs), including thousands of new transposon insertions, and of highly polymorphic and medically important regions such as the human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will facilitate high-quality precision medicine and studies of individual haplotype variation and population diversity.
Keyphrases
- endothelial cells
- copy number
- genome wide
- induced pluripotent stem cells
- emergency department
- machine learning
- mental health
- small molecule
- early onset
- bone marrow
- high resolution
- electronic health record
- single cell
- dna methylation
- gene expression
- mass spectrometry
- big data
- health information
- mesenchymal stem cells
- crystal structure
- social media
- drug induced
- living cells