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PreprintCited by 3Bioinformatics and Genomic NetworksGenomics and Phylogenetic StudiesRNA Research and Splicing

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Selecting genes for analysis using historically contingent progress: from RNA changes to protein-protein interactions

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Lalit, Farhaan, Jose, Antony M·2024·Nucleic Acids Research
DOI 10.1101/2024.05.01.592119PMC PMC11717427

Preprint — published as 10.1093/nar/gkae1246 · Paper page

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Abstract

Progress in biology has generated numerous lists of genes that share some property. But advancing from these lists of genes to understanding their roles is slow and unsystematic. Here we use RNA silencing in C. elegans to illustrate an approach for prioritizing genes for detailed study given limited resources. The partially subjective relationships between genes forged by both deduced functional relatedness and biased progress in the field was captured as mutual information and used to cluster genes that were frequently identified yet remain understudied. Some proteins encoded by these understudied genes are predicted to physically interact with known regulators of RNA silencing, suggesting feedback regulation. Predicted interactions with proteins that act in other processes and the clustering of studied genes among the most frequently perturbed suggest regulatory links connecting RNA silencing to other processes like the cell cycle and asymmetric cell division. Thus, among the gene products altered when a process is perturbed could be regulators of that process acting to restore homeostasis, which provides a way to use RNA sequencing to identify candidate protein-protein interactions. Together, the analysis of perturbed transcripts and potential interactions of the proteins they encode could help prioritize candidate regulators of any process.

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Metadata

Authors
Lalit, F., & Jose, A. M.
Affiliations
University of Maryland, College Park (US)
Corresponding author
Jose, Antony M
ORCID
Jose, Antony M
Venue
Nucleic Acids Research
Publisher
openRxiv
Published
2024-05-03
Volume
53
Issue
1
ISSN
0305-1048 (ISSN-L)
DOI
10.1101/2024.05.01.592119
PMC
PMC11717427
OpenAlex
W4406212263
Cited by
3
References
3
Citations by year
2026: 2 · 2024: 1
FWCI
0.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation (2120895)
  • National Institutes of Health
  • Graduate School, University of Maryland
  • National Institute of General Medical Sciences (R01GM124356)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
gene prioritization, RNA silencing, Caenorhabditis elegans, mutual information, gene clustering, protein-protein interaction, RNA sequencing, feedback regulation, cell cycle, asymmetric cell division, gene regulatory networks, homeostasis, RNA interference

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