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PreprintCited by 81Advanced Proteomics Techniques and ApplicationsBioinformatics and Genomic NetworksGene expression and cancer classification

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Experimental reproducibility limits the correlation between mRNA and protein abundances in tumour proteomic profiles

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Upadhya, Swathi Ramachandra, Ryan, Colm J.·2021·Cell Reports Methods
DOI 10.1101/2021.09.22.461108PMC PMC9499981

Preprint — published as 10.1016/j.crmeth.2022.100288 · Paper page

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Abstract

Large-scale studies of human proteomes have revealed only a moderate correlation between mRNA and protein abundances. It is unclear to what extent this moderate correlation reflects post-transcriptional regulation and to what extent it reflects measurement error. Here, by analysing replicate profiles of tumours and cell lines, we show that there is considerable variation in the reproducibility of measurements of transcripts and proteins from individual genes. Proteins with more reproducible measurements tend to have higher mRNA-protein correlation, suggesting that measurement reproducibility accounts for a substantial fraction of the unexplained variation between mRNA and protein abundances. The reproducibility of individual proteins is somewhat consistent across studies and we exploit this to develop an aggregate reproducibility score that explains a substantial amount of the variation in mRNA-protein correlation across multiple studies. Finally, we show that pathways previously reported to have higher-than-average mRNA-protein correlation may simply contain members that can be more reproducibly quantified.

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Metadata

Authors
Upadhya, S. R., & Ryan, C. J.
Affiliations
University College Dublin (IE)
Corresponding author
Ryan, Colm J.
ORCID
Venue
Cell Reports Methods
Publisher
openRxiv
Published
2021-09-22
Volume
2
Issue
9
Pages
100288-100288
ISSN
2667-2375 (ISSN-L)
DOI
10.1101/2021.09.22.461108
PMC
PMC9499981
OpenAlex
W4296605715
Cited by
81
References
1
Citations by year
2026: 31 · 2025: 20 · 2024: 20 · 2023: 8 · 2022: 2
FWCI
4.52
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell Reports Methods (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University College Dublin
  • Irish Research Council (Laureate Awards 2017/2018, 2017/2018)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Keywords
mRNA-protein correlation, measurement reproducibility, cancer proteomics, post-transcriptional regulation, gene expression profiling, proteomic profiling, measurement error, cancer cell lines
MeSH terms
Gene Expression Regulation, Humans, Neoplasms, RNA, Messenger, Reproducibility of Results, Proteomics

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