DMCA
Genome analysis Consensus generation and variant detection by Celera Assembler
BibTeX
@MISC{Denisov_genomeanalysis,
author = {Gennady Denisov and Brian Walenz and Aaron L. Halpern and Jason Miller and Nelson Axelrod and Samuel Levy and Granger Sutton},
title = {Genome analysis Consensus generation and variant detection by Celera Assembler},
year = {}
}
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Abstract
Motivation: We present an algorithm to identify allelic variation given a Whole Genome Shotgun (WGS) assembly of haploid sequences, and to produce a set of haploid consensus sequences rather than a single consensus sequence. Existing WGS assemblers take a column-by-column approach to consensus generation, and produce a single consensus sequence which can be inconsistent with the underlying haploid alleles, and inconsistent with any of the aligned sequence reads. Our new algorithm uses a dynamic windowing approach. It detects alleles by simultaneously processing the portions of aligned reads spanning a region of sequence variation, assigns reads to their respective alleles, phases adjacent variant alleles and generates a consensus sequence corresponding to each confirmed allele. This algorithm was used to produce the first diploid genome sequence of an individual human. It can also be applied to assemblies of multiple diploid individuals and hybrid assemblies of multiple haploid organisms. Results: Being applied to the individual human genome assembly, the new algorithm detects exactly two confirmed alleles and reports two consensus sequences in 98.98 % of the total number 2 033 311 detected regions of sequence variation. In 33 269 out of 460 373 detected regions of size 41 bp, it fixes the constructed errors of a mosaic haploid representation of a diploid locus as produced by the original Celera Assembler consensus algorithm. Using an optimized procedure calibrated against 1 506 344 known SNPs, it detects 438 814 new heterozygous SNPs with false positive rate 12%. Availability: The open source code is available at:
Keyphrases
genome analysis consensus generation celera assembler variant detection sequence variation detected region consensus sequence single consensus sequence new heterozygous snp respective allele multiple haploid organism hybrid assembly original celera assembler consensus algorithm mosaic haploid representation variant allele dynamic windowing approach haploid sequence multiple diploid individual aligned sequence read whole genome shotgun false positive rate haploid consensus total number wgs assembler allelic variation optimized procedure individual human genome assembly individual human diploid locus first diploid genome sequence aligned read column-by-column approach haploid allele open source code new algorithm detects constructed error
