title: Proteogenomics: Integrating Next-Generation Sequencing and Mass Spectrometry to Characterize Human Proteomic Variation.
abstract: Mass spectrometry-based proteomics has emerged as the leading method for detection, quantification, and characterization of proteins. Nearly all proteomic workflows rely on proteomic databases to identify peptides and proteins, but these databases typically contain a generic set of proteins that lack variations unique to a given sample, precluding their detection. Fortunately, proteogenomics enables the detection of such proteomic variations and can be defined, broadly, as the use of nucleotide sequences to generate candidate protein sequences for mass spectrometry database searching. Proteogenomics is experiencing heightened significance due to two developments: (a) advances in DNA sequencing technologies that have made complete sequencing of human genomes and transcriptomes routine, and (b) the unveiling of the tremendous complexity of the human proteome as expressed at the levels of genes, cells, tissues, individuals, and populations. We review here the field of human proteogenomics, with an emphasis on its history, current implementations, the types of proteomic variations it reveals, and several important applications.
authors.affiliation: Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215; email: gloriam_sheynkman@dfci.harvard.edu.|Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.|Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706; email: mshort@chem.wisc.edu , cesnik@wisc.edu.
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Sheynkman
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706; email: mshort@chem.wisc.edu , cesnik@wisc.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Shortreed
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706; email: mshort@chem.wisc.edu , cesnik@wisc.edu.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cesnik
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706; email: mshort@chem.wisc.edu , cesnik@wisc.edu.|Genome Center of Wisconsin, University of Wisconsin, Madison, Wisconsin 53706; email: smith@chem.wisc.edu.
authors.forename: Lloyd M
authors.initials: LM
authors.lastname: Smith
mesh_terms: D001483:Base Sequence / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D013058:Mass Spectrometry; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D000071696:Proteogenomics
chemical_list: D011506:Proteins
keywords: alternative splicing; customized protein databases; genetic variation; isoforms; novel splice junction; polymorphism; proteoform; proteomics; sample-specific databases; single amino acid variant