title: HMMSplicer: a tool for efficient and sensitive discovery of known and novel splice junctions in RNA-Seq data.
abstract: BACKGROUND
  High-throughput sequencing of an organism's transcriptome, or RNA-Seq, is a valuable and versatile new strategy for capturing snapshots of gene expression. However, transcriptome sequencing creates a new class of alignment problem: mapping short reads that span exon-exon junctions back to the reference genome, especially in the case where a splice junction is previously unknown.
  
  
  RESULTS
  Here we introduce HMMSplicer, an accurate and efficient algorithm for discovering canonical and non-canonical splice junctions in short read datasets. HMMSplicer identifies more splice junctions than currently available algorithms when tested on publicly available A. thaliana, P. falciparum, and H. sapiens datasets without a reduction in specificity.
  
  
  CONCLUSIONS
  HMMSplicer was found to perform especially well in compact genomes and on genes with low expression levels, alternative splice isoforms, or non-canonical splice junctions. Because HHMSplicer does not rely on pre-built gene models, the products of inexact splicing are also detected. For H. sapiens, we find 3.6% of 3' splice sites and 1.4% of 5' splice sites are inexact, typically differing by 3 bases in either direction. In addition, HMMSplicer provides a score for every predicted junction allowing the user to set a threshold to tune false positive rates depending on the needs of the experiment. HMMSplicer is implemented in Python. Code and documentation are freely available at http://derisilab.ucsf.edu/software/hmmsplicer.
authors.affiliation: Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Dimon
authors.forename: Katherine
authors.initials: K
authors.lastname: Sorber
authors.forename: Joseph L
authors.initials: JL
authors.lastname: DeRisi
mesh_terms: D000465:Algorithms; D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D006801:Humans; D010963:Plasmodium falciparum / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D022821:RNA Splice Sites