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

Shaohang Xu1, Ruo Zhou1, Zhe Ren1

  • 1BGI-Shenzhen , 11 Build, Beishan Industrial Zone, Yantian District, Shenzhen 518083, China.

Journal of Proteome Research
|October 27, 2015
PubMed

Insights

Ribosome-bound mRNA (RNC-mRNA) data helps identify missing proteins in liver cancer. Analysis revealed that 93% of these unobserved proteins are difficult to detect due to protein properties or gene expression levels.

Area of Science:

  • Proteomics
  • Transcriptomics
  • Bioinformatics

Background:

  • Mass spectrometry has limitations in identifying all proteins.
  • Ribosome-bound mRNA (RNC-mRNA) profiles can indicate actively translated genes.
  • Understanding missing proteins is crucial for comprehensive proteome analysis.

Purpose of the Study:

  • To investigate the reasons behind 'missing proteins' in liver cancer cell lines.
  • To analyze proteins lacking both RNA-seq and MS/MS evidence.
  • To correlate protein properties and gene-level factors with detection difficulties.

Main Methods:

  • Acquisition of multi-omics data: free-mRNAs, RNC-mRNAs, and proteomes from three liver cancer cell lines.
  • Bioinformatic analysis of missing proteins listed in neXtProt (release 2014-09-19).
  • Evaluation of RNA-seq and MS/MS evidence, physicochemical properties, and gene chromatin structures.

Main Results:

  • 1501 proteins were not detected by either RNC-mRNA or MS/MS.
  • Missing proteins exhibited properties like high hydrophobicity, unsuitable detection characteristics, or sensory functions.
  • Gene-level analysis indicated non-expressing chromatin structures for some missing proteins.
  • 93% of the missing proteins were attributed to detection challenges (protein or gene level).

Conclusions:

  • RNC-mRNA data combined with proteomic and transcriptomic analyses can help explain missing proteins.
  • Protein hydrophobicity, detection limitations, and gene regulatory factors contribute to proteins being 'missing' in omics datasets.
  • This study provides insights into the biological and technical reasons for incomplete proteome coverage in liver cancer.
Keywords:
DNase I hypersensitivity site, undetectable proteinsENCODEMS/MS, DHSRNA-seqRNC-mRNAmRNAmissing protein

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