Selecting genes for analysis using historically contingent progress: from RNA changes to protein–protein interactions
Open accessPublished 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
- ORCID
- Jose, Antony M
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2025-01-07
- Volume
- 53
- Issue
- 1
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC11717427
- OpenAlex
- W4406212263
- Cited by
- 3
- References
- 87
- Citations by year
- 2026: 2 · 2024: 1
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- 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 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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