RRC ID 80892
Author Ribeiro C, Farmer CK, de Magalhães JP, Freitas AA.
Title Predicting lifespan-extending chemical compounds for C. elegans with machine learning and biologically interpretable features.
Journal Aging (Albany NY)
Abstract Recently, there has been a growing interest in the development of pharmacological interventions targeting ageing, as well as in the use of machine learning for analysing ageing-related data. In this work, we use machine learning methods to analyse data from DrugAge, a database of chemical compounds (including drugs) modulating lifespan in model organisms. To this end, we created four types of datasets for predicting whether or not a compound extends the lifespan of C. elegans (the most frequent model organism in DrugAge), using four different types of predictive biological features, based on: compound-protein interactions, interactions between compounds and proteins encoded by ageing-related genes, and two types of terms annotated for proteins targeted by the compounds, namely Gene Ontology (GO) terms and physiology terms from the WormBase's Phenotype Ontology. To analyse these datasets, we used a combination of feature selection methods in a data pre-processing phase and the well-established random forest algorithm for learning predictive models from the selected features. In addition, we interpreted the most important features in the two best models in light of the biology of ageing. One noteworthy feature was the GO term "Glutathione metabolic process", which plays an important role in cellular redox homeostasis and detoxification. We also predicted the most promising novel compounds for extending lifespan from a list of previously unlabelled compounds. These include nitroprusside, which is used as an antihypertensive medication. Overall, our work opens avenues for future work in employing machine learning to predict novel life-extending compounds.
Volume 15(13)
Pages 6073-6099
Published 2023-7-13
DOI 10.18632/aging.204866
PII 204866
PMID 37450404
PMC PMC10373959
MeSH Aging Algorithms Caenorhabditis elegans* / drug effects Caenorhabditis elegans* / genetics Caenorhabditis elegans* / physiology Databases, Pharmaceutical Gene Ontology Glutathione / analysis Longevity* / drug effects Machine Learning* Oxidation-Reduction
C.elegans tm344