comparing de novo genome assembly the long and short of it比较新创基因组组装它的长和短.pdf

Comparing De Novo Genome Assembly: The Long and Short of It 1 1,2 Giuseppe Narzisi *, Bud Mishra 1 Courant Institute of Mathematical Sciences, New York University, New York, New York, United States of America, 2 NYU School of Medicine, New York University, New York, New York, United States of America Abstract Recent advances in DNA sequencing technology and their focal role in Genome Wide Association Studies (GWAS) have rekindled a growing interest in the whole-genome sequence assembly (WGSA) problem, thereby, inundating the field with a plethora of new formalizations, algorithms, heuristics and implementations. And yet, scant attention has been paid to comparative assessments of these assemblers’ quality and accuracy. No commonly accepted and standardized method for comparison exists yet. Even worse, widely used metrics to compare the assembled sequences emphasize only size, poorly capturing the contig quality and accuracy. This paper addresses these concerns: it highlights common anomalies in assembly accuracy through a rigorous study of several assemblers, compared under both standard metrics (N50, coverage, contig sizes, etc.) as well as a more comprehensive metric (Feature-Response Curves, FRC) that is introduced here; FRC transparently captures the trade-offs between contigs’ quality against their sizes. For this purpose, most of the publicly available major sequence assemblers – both for low-coverage long (Sanger) and high-coverage short (Illumina) reads technologies – are compared. These assemblers are applied to microbial (Escherichia coli, Brucella, Wolbachia, Staphylococcus, Helicobacter) and partial human genome sequences (Chr. Y), using sequence reads of various read- leng