GAIT-GM integrative cross-omics analyses reveal cholinergic defects in a C. elegans model of Parkinson's disease. Author Lauren McIntyre, Francisco Huertas, Alison Morse, Rachel Kaletsky, Coleen Murphy, Vrinda Kalia, Gary Miller, Olexander Moskalenko, Ana Conesa, Danielle Mor Publication Year 2022 Type Journal Article Abstract Parkinson's disease (PD) is a disabling neurodegenerative disorder in which multiple cell types, including dopaminergic and cholinergic neurons, are affected. The mechanisms of neurodegeneration in PD are not fully understood, limiting the development of therapies directed at disease-relevant molecular targets. C. elegans is a genetically tractable model system that can be used to disentangle disease mechanisms in complex diseases such as PD. Such mechanisms can be studied combining high-throughput molecular profiling technologies such as transcriptomics and metabolomics. However, the integrative analysis of multi-omics data in order to unravel disease mechanisms is a challenging task without advanced bioinformatics training. Galaxy, a widely-used resource for enabling bioinformatics analysis by the broad scientific community, has poor representation of multi-omics integration pipelines. We present the integrative analysis of gene expression and metabolite levels of a C. elegans PD model using GAIT-GM, a new Galaxy tool for multi-omics data analysis. Using GAIT-GM, we discovered an association between branched-chain amino acid metabolism and cholinergic neurons in the C. elegans PD model. An independent follow-up experiment uncovered cholinergic neurodegeneration in the C. elegans model that is consistent with cholinergic cell loss observed in PD. GAIT-GM is an easy to use Galaxy-based tool for generating novel testable hypotheses of disease mechanisms involving gene-metabolite relationships. Keywords Animals, Disease Models, Animal, Caenorhabditis elegans, Dopamine, Parkinson Disease, Cholinergic Agents, Cholinergic Neurons Journal Sci Rep Volume 12 Issue 1 Pages 3268 Date Published 2022 Feb 28 ISSN Number 2045-2322 DOI 10.1038/s41598-022-07238-9 Alternate Journal Sci Rep PMCID PMC8885929 PMID 35228596 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML