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

Bioinformatics (Oxford, England) - Tập 26 Số 7 - Trang 873-881 - 2010
Thomas D. Wu1, Şerban Nacu1
1Department of Bioinformatics, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA

Tóm tắt

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:  [email protected]

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Tài liệu tham khảo

Bhangale, 2005, Comprehensive identification and characterization of diallelic insertion-deletion polymorphisms in 330 human candidate genes, Hum. Mol. Genet., 14, 59, 10.1093/hmg/ddi006

Bona, 2008, Optimal spliced alignments of short sequence reads, Bioinformatics, 24, i174, 10.1093/bioinformatics/btn300

Burrows, 1994, A block-sorting lossless data compression algorithm, Technical Report 124.

Canales, 2006, Evaluation of DNA microarray results with quantitative gene expression platforms, Nat. Biotechnol., 24, 1115, 10.1038/nbt1236

Cao, 2002, Locus-specific control of asymmetric and CpNpG methylation by the DRM and CMT3 methyltransferase genes, Proc. Natl Acad. Sci., 99, 16491, 10.1073/pnas.162371599

Deng, 2009, Targeted bisulfite sequencing reveals changes in DNA methylation associated with nuclear reprogramming, Nat. Biotechnol., 27, 353, 10.1038/nbt.1530

Dintilhac, 2004, A conserved non-homeodomain Hoxa9 isoform interacting with CBP is co-expressed with the ‘typical’ Hoxa9 protein during embryogenesis, Gene Expression Patterns, 4, 215, 10.1016/j.modgep.2003.08.006

Goll, 2005, Eukaryotic cytosine methyltransferases, Annu. Rev. Biochem., 74, 481, 10.1146/annurev.biochem.74.010904.153721

Hampton, 2009, A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome, Genome Res., 19, 167, 10.1101/gr.080259.108

Hwang, 1980, A simple algorithm for merging two disjoint linearly ordered sets, SIAM J. Comput., 1, 31, 10.1137/0201004

Jiang, 2008, SeqMap: mapping massive amount of oligonucleotides to the genome, Bioinformatics, 24, 2395, 10.1093/bioinformatics/btn429

Kent, 2002, BLAT—the BLAST-like alignment tool, Genome Research, 12, 656

Knuth, 1973, The Art of Computer Programming: Sorting and Searching

Langmead, 2009, Ultrafast and memory-efficient alignment of short dna sequences to the human genome, Genome Biology, 10, R25, 10.1186/gb-2009-10-3-r25

Li, 2009, Fast and accurate short read alignment with Burrows-Wheeler Transform, Bioinformatics, 25, 1754, 10.1093/bioinformatics/btp324

Li, 2008, Mapping short DNA sequencing reads and calling variants using mapping quality scores, Genome Res., 18, 1851, 10.1101/gr.078212.108

Li, 2008, SOAP: short oligonucleotide alignment program, Bioinformatics, 24, 713, 10.1093/bioinformatics/btn025

Li, 2009, SOAP2: an improved ultrafast tool for short read alignment, Bioinformatics, 25, 1966, 10.1093/bioinformatics/btp336

Lister, 2009, Finding the fifth base: Genome-wide sequencing of cytosine methylation, Genome Research, 19, 959, 10.1101/gr.083451.108

Manber, 1993, Suffix arrays: a new method for on-line string searches, SIAM J. Comput., 22, 935, 10.1137/0222058

Manske, 2009, SNP-o-matic, Bioinformatics, 25, 2434, 10.1093/bioinformatics/btp403

Nethercote, 2007, Valgrind: a framework for heavyweight dynamic binary instrumentation, Proceedings of the 2007 ACM SIGPLAN Conference on Programming Language Design and Implementation, 89, 10.1145/1250734.1250746

Ning, 2001, SSAHA: a fast search method for large DNA databases, Genome Res., 11, 1725, 10.1101/gr.194201

Rasmussen, 2006, Efficient q-gram filters for finding all ε-matches over a given length, J. Comput. Biol., 13, 296, 10.1089/cmb.2006.13.296

Rumble, 2009, SHRiMP: accurate mapping of color-space reads, PLoS Comput. Biol., 5, e1000386, 10.1371/journal.pcbi.1000386

Sherry, 2001, dbSNP: the NCBI database of genetic variation, Nucleic Acids Res., 29, 308, 10.1093/nar/29.1.308

Smith, 2008, Using quality scores and longer reads improves accuracy of Solexa read mapping, BMC Bioinformatics, 9, 128, 10.1186/1471-2105-9-128

Trapnell, 2009, TopHat: discovering splice junctions with RNA-Seq, Bioinformatics, 25, 1105, 10.1093/bioinformatics/btp120

Wang, 2008, Alternative isoform regulation in human tissue transcriptomes, Nature, 456, 470, 10.1038/nature07509

Weber, 2002, Human diallelic insertion/deletion polymorphisms, Am. J. Hum. Genet., 71, 854, 10.1086/342727

Weese, 2009, RazerS—fast read mapping with sensitivity control, Genome Res., 19, 1646, 10.1101/gr.088823.108

Wu, 2005, GMAP: a genomic mapping and alignment program for mRNA and EST sequences, Bioinformatics, 21, 1859, 10.1093/bioinformatics/bti310

Yeo, 2004, Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals, J. Comput. Biol., 11, 377, 10.1089/1066527041410418

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Thông tin xuất bản

Bioinformatics (Oxford, England)

Tập 26 Số 7

873-881

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