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Predicting “pain genes”: multi-modal data integration using probabilistic classifiers and interaction networks

Abstract:
Accurate identification of pain-related genes remains challenging due to the complex nature of pain pathophysiology and the subjective nature of pain reporting in humans, or inferring pain states in animals on the basis of behaviour. Here, we use a machine learning approach to identify possible “pain genes”. Labelling was based on a gold-standard list of genes with validated involvement across pain conditions, and was trained on a selection of -omics, protein-protein interaction network features, and biological function readouts for each gene. Multiple classifiers were trained, and the top-performing model was selected to predict a “pain score” per gene. The top ranked genes were validated against pain-related human SNPs to validate against human genetics studies. Functional analysis revealed JAK2/STAT3 signal, ErbB, and Rap1 signalling pathways as promising targets for further exploration, while network topological features contribute significantly to the identification of “pain” genes. As such, a network based on top-ranked genes was constructed to reveal previously uncharacterised pain-related genes including CHRFAM7A and UNC79. These analyses can be further explored using the linked open-source database at https://livedataoxford.shinyapps.io/drg-directory/, which is accompanied by a freely accessible code template and user guide for wider adoption across disciplines. Together, the novel insights into pain pathogenesis can indicate promising directions for future experimental research.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1093/bioadv/vbae156

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author
ORCID:
0000-0001-9237-5878
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Clinical Neurosciences
Role:
Author


More from this funder
Funder identifier:
https://ror.org/001aqnf71
Grant:
MR/W002388/1


Publisher:
Oxford University Press
Journal:
Bioinformatics Advances More from this journal
Volume:
4
Issue:
1
Article number:
vbae156
Publication date:
2024-10-18
Acceptance date:
2024-10-15
DOI:
EISSN:
2635-0041


Language:
English
Keywords:
Pubs id:
2041760
Local pid:
pubs:2041760
Deposit date:
2024-10-25

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