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J Proteome Res. 2015 Dec 4;14(12):4976-84. doi: 10.1021/acs.jproteome.5b00476. Epub 2015 Nov 5.

Appraisal of the Missing Proteins Based on the mRNAs Bound to Ribosomes.

Xu S1, Zhou R1, Ren Z1, Zhou B1, Lin Z1, Hou G1,2, Deng Y1,2, Zi J1, Lin L1, Wang Q1,2, Liu X1, Xu X1, Wen B1, Liu S1,2.

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BGI-Shenzhen , 11 Build, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences , BeiChen West Road, Beijing 100101, China.


Considering the technical limitations of mass spectrometry in protein identification, the mRNAs bound to ribosomes (RNC-mRNA) are assumed to reflect the mRNAs participating in the translational process. The RNC-mRNA data are reasoned to be useful for appraising the missing proteins. A set of the multiomics data including free-mRNAs, RNC-mRNAs, and proteomes was acquired from three liver cancer cell lines. On the basis of the missing proteins in neXtProt (release 2014-09-19), the bioinformatics analysis was carried out in three phases: (1) finding how many neXtProt missing proteins have or do not have RNA-seq and/or MS/MS evidence, (2) analyzing specific physicochemical and biological properties of the missing proteins that lack both RNA-seq and MS/MS evidence, and (3) analyzing the combined properties of these missing proteins. Total of 1501 missing proteins were found by neither RNC-mRNA nor MS/MS in the three liver cancer cell lines. For these missing proteins, some are expected higher hydrophobicity, unsuitable detection, or sensory functions as properties at the protein level, while some are predicted to have nonexpressing chromatin structures on the corresponding gene level. With further integrated analysis, we could attribute 93% of them (1391/1501) to these causal factors, which result in the expression products scarcely detected by RNA-seq or MS/MS.


DNase I hypersensitivity site, undetectable proteins; ENCODE; MS/MS, DHS; RNA-seq; RNC-mRNA; mRNA; missing protein

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