NovoGraph: Human genome graph construction from multiple long-read de novo assemblies

Biederstedt, E., Oliver, J. C., Hansen, N. F., Jajoo, A., Dunn, N., Olson, A., Busby, B., Dilthey, A. T. (September 2018) NovoGraph: Human genome graph construction from multiple long-read de novo assemblies. F1000Res, 7. p. 1391. ISSN 2046-1402

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Abstract

Genome graphs are emerging as an important novel approach to the analysis of high-throughput human sequencing data. By explicitly representing genetic variants and alternative haplotypes in a mappable data structure, they can enable the improved analysis of structurally variable and hyperpolymorphic regions of the genome. In most existing approaches, graphs are constructed from variant call sets derived from short-read sequencing. As long-read sequencing becomes more cost-effective and enables de novo assembly for increasing numbers of whole genomes, a method for the direct construction of a genome graph from sets of assembled human genomes would be desirable. Such assembly-based genome graphs would encompass the wide spectrum of genetic variation accessible to long-read-based de novo assembly, including large structural variants and divergent haplotypes. Here we present NovoGraph, a method for the construction of a human genome graph directly from a set of de novo assemblies. NovoGraph constructs a genome-wide multiple sequence alignment of all input contigs and creates a graph by merging the input sequences at positions that are both homologous and sequence-identical. NovoGraph outputs resulting graphs in VCF format that can be loaded into third-party genome graph toolkits. To demonstrate NovoGraph, we construct a genome graph with 23,478,835 variant sites and 30,582,795 variant alleles from de novo assemblies of seven ethnically diverse human genomes (AK1, CHM1, CHM13, HG003, HG004, HX1, NA19240). Initial evaluations show that mapping against the constructed graph reduces the average mismatch rate of reads from sample NA12878 by approximately 0.2%, albeit at a slightly increased rate of reads that remain unmapped.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > alignment bioinformatics > genomics and proteomics > analysis and processing > alignment processing bioinformatics > genomics and proteomics > analysis and processing bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment bioinformatics > genomics and proteomics > alignment > sequence alignment Investigative techniques and equipment > assays bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > single nucleotide polymorphism > haplotype bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > single nucleotide polymorphism Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:	Olson, Andrew J.
Communities:	CSHL labs > Ware lab
Depositing User:	Matthew Dunn
Date:	3 September 2018
Date Deposited:	10 Jan 2019 21:50
Last Modified:	06 Feb 2024 21:10
PMCID:	PMC6305223
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/37663

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