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

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.