DOI: 10.1093/bioinformatics/btq057. Fast and SNP-tolerant detection of complex variants and splicing in short reads

Fast and SNP-tolerant detection of complex variants and splicing in short reads

10.1093/bioinformatics/btq057

Crossref journal-article

Oxford University Press (OUP)

Bioinformatics (286)

Abstract

Abstract Motivation: Next-generation sequencing captures sequence differences in reads relative to a reference genome or transcriptome, including splicing events and complex variants involving multiple mismatches and long indels. We present computational methods for fast detection of complex variants and splicing in short reads, based on a successively constrained search process of merging and filtering position lists from a genomic index. Our methods are implemented in GSNAP (Genomic Short-read Nucleotide Alignment Program), which can align both single- and paired-end reads as short as 14 nt and of arbitrarily long length. It can detect short- and long-distance splicing, including interchromosomal splicing, in individual reads, using probabilistic models or a database of known splice sites. Our program also permits SNP-tolerant alignment to a reference space of all possible combinations of major and minor alleles, and can align reads from bisulfite-treated DNA for the study of methylation state. Results: In comparison testing, GSNAP has speeds comparable to existing programs, especially in reads of ≥70 nt and is fastest in detecting complex variants with four or more mismatches or insertions of 1–9 nt and deletions of 1–30 nt. Although SNP tolerance does not increase alignment yield substantially, it affects alignment results in 7–8% of transcriptional reads, typically by revealing alternate genomic mappings for a read. Simulations of bisulfite-converted DNA show a decrease in identifying genomic positions uniquely in 6% of 36 nt reads and 3% of 70 nt reads. Availability: Source code in C and utility programs in Perl are freely available for download as part of the GMAP package at http://share.gene.com/gmap. Contact: twu@gene.com

Bibliography

Wu, T. D., & Nacu, S. (2010). Fast and SNP-tolerant detection of complex variants and splicing in short reads. Bioinformatics, 26(7), 873â881.

Authors 2

Thomas D. Wu (first)
Serban Nacu (additional)

References 33 Referenced 1,715

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Dates

Type	When
Created	15 years, 6 months ago (Feb. 10, 2010, 10:43 p.m.)
Deposited	2 years, 7 months ago (Jan. 25, 2023, 3:06 a.m.)
Indexed	29 minutes ago (Sept. 3, 2025, 5:34 a.m.)
Issued	15 years, 6 months ago (Feb. 10, 2010)
Published	15 years, 6 months ago (Feb. 10, 2010)
Published Online	15 years, 6 months ago (Feb. 10, 2010)
Published Print	15 years, 5 months ago (April 1, 2010)

Funders 0

None

BibTeX

@article{Wu_2010, title={Fast and SNP-tolerant detection of complex variants and splicing in short reads}, volume={26}, ISSN={1367-4803}, url={http://dx.doi.org/10.1093/bioinformatics/btq057}, DOI={10.1093/bioinformatics/btq057}, number={7}, journal={Bioinformatics}, publisher={Oxford University Press (OUP)}, author={Wu, Thomas D. and Nacu, Serban}, year={2010}, month=feb, pages={873–881} }

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