title: Topograph, a software platform for precursor enrichment corrected global protein turnover measurements.
abstract: Defects in protein turnover have been implicated in a broad range of diseases, but current proteomics methods of measuring protein turnover are limited by the software tools available. Conventional methods require indirect approaches to differentiate newly synthesized protein when synthesized from partially labeled precursor pools. To address this, we have developed Topograph, a software platform which calculates the fraction of peptides that are from newly synthesized proteins and their turnover rates. A unique feature of Topograph is the ability to calculate amino acid precursor pool enrichment levels which allows for accurate calculations when the precursor pool is not fully labeled, and the approach used by Topograph is applicable regardless of the stable isotope label used. We validate the Topograph algorithms using data acquired from a mouse labeling experiment and demonstrate the influence that precursor pool corrections can have on protein turnover measurements.
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hsieh
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shulman
authors.forename: Dao-Fu
authors.initials: DF
authors.lastname: Dai
authors.forename: Evelyn S
authors.initials: ES
authors.lastname: Vincow
authors.forename: Pabalu P
authors.initials: PP
authors.lastname: Karunadharma
authors.forename: Leo
authors.initials: L
authors.lastname: Pallanck
authors.forename: Peter S
authors.initials: PS
authors.lastname: Rabinovitch
authors.forename: Michael J
authors.initials: MJ
authors.lastname: MacCoss
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012984:Software
chemical_list: D000596:Amino Acids; D024101:Mitochondrial Proteins; D010455:Peptides