title: Comparative analysis of algorithms for next-generation sequencing read alignment.
abstract: BACKGROUND
  The advent of next-generation sequencing (NGS) techniques presents many novel opportunities for many applications in life sciences. The vast number of short reads produced by these techniques, however, pose significant computational challenges. The first step in many types of genomic analysis is the mapping of short reads to a reference genome, and several groups have developed dedicated algorithms and software packages to perform this function. As the developers of these packages optimize their algorithms with respect to various considerations, the relative merits of different software packages remain unclear. However, for scientists who generate and use NGS data for their specific research projects, an important consideration is choosing the software that is most suitable for their application.
  
  
  RESULTS
  With a view to comparing existing short read alignment software, we develop a simulation and evaluation suite, Seal, which simulates NGS runs for different configurations of various factors, including sequencing error, indels and coverage. We also develop criteria to compare the performances of software with disparate output structure (e.g. some packages return a single alignment while some return multiple possible alignments). Using these criteria, we comprehensively evaluate the performances of Bowtie, BWA, mr- and mrsFAST, Novoalign, SHRiMP and SOAPv2, with regard to accuracy and runtime.
  
  
  CONCLUSIONS
  We expect that the results presented here will be useful to investigators in choosing the alignment software that is most suitable for their specific research aims. Our results also provide insights into the factors that should be considered to use alignment results effectively. Seal can also be used to evaluate the performance of algorithms that use deep sequencing data for various purposes (e.g. identification of genomic variants).
  
  
  BACKGROUND
  Seal is available as open source at http://compbio.case.edu/seal/.
  
  
  BACKGROUND
  matthew.ruffalo@case.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, OH 44106, USA. matthew.ruffalo@case.edu
authors.forename: Matthew
authors.initials: M
authors.lastname: Ruffalo
authors.forename: Thomas
authors.initials: T
authors.lastname: LaFramboise
authors.forename: Mehmet
authors.initials: M
authors.lastname: Koyutürk
mesh_terms: D000465:Algorithms; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054643:INDEL Mutation; D016415:Sequence Alignment / Q000379:methods*; D012984:Software