Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities

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 p...

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Main Authors: Sébastien Leblanc, Marie A. Brunet, Jean-François Jacques, Amina M. Lekehal, Andréa Duclos, Alexia Tremblay, Alexis Bruggeman-Gascon, Sondos Samandi, Mylène Brunelle, Alan A. Cohen, Michelle S. Scott, Xavier Roucou
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Genomics, Proteomics & Bioinformatics
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Online Access:http://www.sciencedirect.com/science/article/pii/S1672022922001243
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author Sébastien Leblanc
Marie A. Brunet
Jean-François Jacques
Amina M. Lekehal
Andréa Duclos
Alexia Tremblay
Alexis Bruggeman-Gascon
Sondos Samandi
Mylène Brunelle
Alan A. Cohen
Michelle S. Scott
Xavier Roucou
author_facet Sébastien Leblanc
Marie A. Brunet
Jean-François Jacques
Amina M. Lekehal
Andréa Duclos
Alexia Tremblay
Alexis Bruggeman-Gascon
Sondos Samandi
Mylène Brunelle
Alan A. Cohen
Michelle S. Scott
Xavier Roucou
author_sort Sébastien Leblanc
collection DOAJ
description 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 high-throughput 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.
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spelling doaj.art-7063003343fe4f088a982f401b17848e2023-12-30T04:42:50ZengElsevierGenomics, Proteomics & Bioinformatics1672-02292023-06-01213515534Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein CommunitiesSébastien Leblanc0Marie A. Brunet1Jean-François Jacques2Amina M. Lekehal3Andréa Duclos4Alexia Tremblay5Alexis Bruggeman-Gascon6Sondos Samandi7Mylène Brunelle8Alan A. Cohen9Michelle S. Scott10Xavier Roucou11Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada; PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec City, QC G1V 0A6, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada; PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec City, QC G1V 0A6, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada; PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec City, QC G1V 0A6, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada; PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec City, QC G1V 0A6, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada; PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec City, QC G1V 0A6, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada; PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec City, QC G1V 0A6, CanadaDepartment of Family Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1E 4K8, Canada; PROTEO, Quebec Network for Research on Protein Function, Structure, and Engineering, Quebec City, QC G1V 0A6, Canada; Corresponding author.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 high-throughput 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.http://www.sciencedirect.com/science/article/pii/S1672022922001243Alternative proteinProtein networkProtein–protein interactionPseudogeneAffinity purification mass spectrometry
spellingShingle Sébastien Leblanc
Marie A. Brunet
Jean-François Jacques
Amina M. Lekehal
Andréa Duclos
Alexia Tremblay
Alexis Bruggeman-Gascon
Sondos Samandi
Mylène Brunelle
Alan A. Cohen
Michelle S. Scott
Xavier Roucou
Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities
Genomics, Proteomics & Bioinformatics
Alternative protein
Protein network
Protein–protein interaction
Pseudogene
Affinity purification mass spectrometry
title Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities
title_full Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities
title_fullStr Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities
title_full_unstemmed Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities
title_short Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities
title_sort newfound coding potential of transcripts unveils missing members of human protein communities
topic Alternative protein
Protein network
Protein–protein interaction
Pseudogene
Affinity purification mass spectrometry
url http://www.sciencedirect.com/science/article/pii/S1672022922001243
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