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

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

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Lalit, Farhaan, Jose, Antony M·2025·Nucleic Acids Research

Published version of a preprint

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 Caenorhabditis 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 were 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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Authors
Lalit, F., & Jose, A. M.
Affiliations
University of Maryland, College Park (US)
Corresponding author
Jose, Antony M
Venue
Nucleic Acids Research
Published
2025-01-07
Volume
53
Issue
1
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W4406212263
Cited by
3
References
87
Citations by year
2026: 2 · 2024: 1
FWCI
0.41
Type
journal article
Language
en
Open access
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 Institutes of Health (R01GM124356)
  • National Science Foundation (2120895])
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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