title: Unveiling alterative splice diversity from human oligodendrocyte proteome data.
abstract: Oligodendrocytes produce and maintain the myelin sheath of axons in the central nervous system. Because misassembled myelin sheaths have been associated with brain disorders such as multiple sclerosis and schizophrenia, recent advances have been made towards the description of the oligodendrocyte proteome. The identification of splice variants represented in the proteome is as important as determining the level of oligodendrocyte-associated proteins. Here, we used an oligodendrocyte proteome dataset deposited in ProteomeXchange to search against a customized protein sequence file containing computationally predicted splice variants. Our approach resulted in the identification of 39 splice variants, including one variant from the GTPase KRAS gene and another from the human glutaminase gene family. We also detected the mRNA expression of five selected splice variants and demonstrated that a fraction of these have their canonical proteins participating in direct protein-protein interactions. In conclusion, we believe our findings contribute to the molecular characterization of oligodendrocytes and may encourage other research groups working with central nervous system disorders to investigate the biological significance of these splice variants. The splice variants identified in this study may encode proteins that could be targeted in novel treatment strategies and diagnostic methods.
  
  
  
  Several disorders of the central nervous system (CNS) are associated with misassembled myelin sheaths, which are produced and maintained by oligodendrocytes (OL). Recently, the OL proteome has been explored to identify key proteins and molecular functions associated with CNS disorders. We developed an innovative approach to select, with a higher level of confidence, a relevant list of splice variants from a proteome dataset and detected the mRNA expression of five selected variants: EEF1D, KRAS, MFF, SDR39U1, and SUGT1. We also described splice variants extracted from OL proteome data. Among the splice variants identified, some are from genes previously linked to CNS and related disorders. Our findings may contribute to oligodendrocyte characterization and encourage other research groups to investigate the biological role of splice variants and to improve current treatments and diagnostic methods for CNS disorders.
authors.affiliation: Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ, Brazil; Bioinformatics Unit, Clinical Research Coordination, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
authors.forename: Raphael
authors.initials: R
authors.lastname: Tavares
authors.affiliation: Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ, Brazil; Bioinformatics Unit, Clinical Research Coordination, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Wajnberg
authors.affiliation: Bioinformatics Unit, Clinical Research Coordination, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
authors.forename: Nicole de Miranda
authors.initials: NM
authors.lastname: Scherer
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências (LNBio), CNPEM, Campinas, SP, Brazil.
authors.forename: Bianca Alves
authors.initials: BA
authors.lastname: Pauletti
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Cassoli
authors.affiliation: Clinical Research Coordination, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
authors.forename: Carlos Gil
authors.initials: CG
authors.lastname: Ferreira
authors.affiliation: Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências (LNBio), CNPEM, Campinas, SP, Brazil.
authors.forename: Adriana Franco
authors.initials: AF
authors.lastname: Paes Leme
authors.affiliation: Department of Immunobiology, Fluminense Federal University (UFF), Niterói, RJ, Brazil; Program of Cellular Biology, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
authors.forename: Patricia Savio
authors.initials: PS
authors.lastname: de Araujo-Souza
authors.affiliation: Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martins-de-Souza
authors.affiliation: Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ, Brazil; Bioinformatics Unit, Clinical Research Coordination, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil. Electronic address: passetti@fiocruz.br.
authors.forename: Fabio
authors.initials: F
authors.lastname: Passetti
mesh_terms: D017398:Alternative Splicing; D015415:Biomarkers; D002493:Central Nervous System Diseases / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D030562:Databases, Protein; D005972:Glutaminase / Q000235:genetics; D006801:Humans; D009836:Oligodendroglia / Q000737:chemistry*; D020543:Proteome / Q000032:analysis*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: D015415:Biomarkers; C117307:KRAS protein, human; D020543:Proteome; D005972:Glutaminase; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Alternative splicing; Bioinformatics; Oligodendrocytes; Proteogenomics; Proteomics