title: MSProGene: integrative proteogenomics beyond six-frames and single nucleotide polymorphisms.
abstract: Ongoing advances in high-throughput technologies have facilitated accurate proteomic measurements and provide a wealth of information on genomic and transcript level. In proteogenomics, this multi-omics data is combined to analyze unannotated organisms and to allow more accurate sample-specific predictions. Existing analysis methods still mainly depend on six-frame translations or reference protein databases that are extended by transcriptomic information or known single nucleotide polymorphisms (SNPs). However, six-frames introduce an artificial sixfold increase of the target database and SNP integration requires a suitable database summarizing results from previous experiments. We overcome these limitations by introducing MSProGene, a new method for integrative proteogenomic analysis based on customized RNA-Seq driven transcript databases. MSProGene is independent from existing reference databases or annotated SNPs and avoids large six-frame translated databases by constructing sample-specific transcripts. In addition, it creates a network combining RNA-Seq and peptide information that is optimized by a maximum-flow algorithm. It thereby also allows resolving the ambiguity of shared peptides for protein inference. We applied MSProGene on three datasets and show that it facilitates a database-independent reliable yet accurate prediction on gene and protein level and additionally identifies novel genes.
  
  
  METHODS
  MSProGene is written in Java and Python. It is open source and available at http://sourceforge.net/projects/msprogene/.
authors.affiliation: Research Group Bioinformatics (NG4), Robert Koch Institute, 13353 Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Zickmann
authors.affiliation: Research Group Bioinformatics (NG4), Robert Koch Institute, 13353 Berlin, Germany.
authors.forename: Bernhard Y
authors.initials: BY
authors.lastname: Renard
mesh_terms: D000465:Algorithms; D000818:Animals; D001473:Bartonella / Q000235:genetics; D030541:Databases, Genetic; D005370:Filarioidea / Q000235:genetics; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods*; D013058:Mass Spectrometry; D010455:Peptides / Q000737:chemistry; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D017423:Sequence Analysis, RNA; D012984:Software
chemical_list: D010455:Peptides; D011506:Proteins