Recent proteogenomic approaches have led to the discovery that regions of the transcriptome previously annotated as non-coding regions[i.e.,untranslated regions(UTRs),open reading frames overlapping annotated coding s...Recent proteogenomic approaches have led to the discovery that regions of the transcriptome previously annotated as non-coding regions[i.e.,untranslated regions(UTRs),open reading frames overlapping annotated coding sequences in a different reading frame,and non-coding RNAs]frequently encode proteins,termed alternative proteins(altProts).This suggests that previously identified protein–protein interaction(PPI)networks are partially incomplete because altProts are not present in conventional protein databases.Here,we used the proteogenomic resource OpenProt and a combined spectrum-and peptide-centric analysis for the re-analysis of a highthroughput human network proteomics dataset,thereby revealing the presence of 261 altProts in the network.We found 19 genes encoding both an annotated(reference)and an alternative protein interacting with each other.Of the 117 altProts encoded by pseudogenes,38 are direct interactors of reference proteins encoded by their respective parental genes.Finally,we experimentally validate several interactions involving altProts.These data improve the blueprints of the human PPI network and suggest functional roles for hundreds of altProts.展开更多
基金supported by the Canadian Institutes for Health Research(CIHR)(Grant No.PJT175322)by a Canada Research Chair in Functional Proteomics and Discovery of Novel Proteins to Xavier Roucou.
文摘Recent proteogenomic approaches have led to the discovery that regions of the transcriptome previously annotated as non-coding regions[i.e.,untranslated regions(UTRs),open reading frames overlapping annotated coding sequences in a different reading frame,and non-coding RNAs]frequently encode proteins,termed alternative proteins(altProts).This suggests that previously identified protein–protein interaction(PPI)networks are partially incomplete because altProts are not present in conventional protein databases.Here,we used the proteogenomic resource OpenProt and a combined spectrum-and peptide-centric analysis for the re-analysis of a highthroughput human network proteomics dataset,thereby revealing the presence of 261 altProts in the network.We found 19 genes encoding both an annotated(reference)and an alternative protein interacting with each other.Of the 117 altProts encoded by pseudogenes,38 are direct interactors of reference proteins encoded by their respective parental genes.Finally,we experimentally validate several interactions involving altProts.These data improve the blueprints of the human PPI network and suggest functional roles for hundreds of altProts.