Enhanced Missing Proteins Detection in NCI60 Cell Lines Using an Integrative Search Engine Approach

The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this...

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Published inJournal of proteome research Vol. 16; no. 12; pp. 4374 - 4390
Main Authors Guruceaga, Elizabeth, Garin-Muga, Alba, Prieto, Gorka, Bejarano, Bartolomé, Marcilla, Miguel, Marín-Vicente, Consuelo, Perez-Riverol, Yasset, Casal, J. Ignacio, Vizcaíno, Juan Antonio, Corrales, Fernando J, Segura, Victor
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 01.12.2017
Subjects
Cell Line, Tumor
Humans
Knowledge Bases
Proteins - analysis
Proteome - analysis
Proteomics - methods
Search Engine
Software
integration of search engines
missing proteins
peptide detectability
C-HPP
NCI60
CCLE
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Summary:The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments. In this work, we used all the proteomic experiments from the NCI60 cell lines and applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem. This workflow benefits from the complementarity of these search engines to increase the proteome coverage. Five missing proteins C-HPP guidelines compliant were identified, although further validation is needed. Moreover, 165 missing proteins were detected with only one unique peptide, and their functional analysis supported their participation in cellular pathways as was also proposed in other studies. Finally, we performed a combined analysis of the gene expression levels and the proteomic identifications from the common cell lines between the NCI60 and the CCLE project to suggest alternatives for further validation of missing protein observations.
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ISSN:1535-3893
1535-3907
DOI:10.1021/acs.jproteome.7b00388