Title | GAIT-GM integrative cross-omics analyses reveal cholinergic defects in a C. elegans model of Parkinson's disease. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | McIntyre, LM, Huertas, F, Morse, AM, Kaletsky, R, Murphy, CT, Kalia, V, Miller, GW, Moskalenko, O, Conesa, A, Mor, DE |
Journal | Sci Rep |
Volume | 12 |
Issue | 1 |
Pagination | 3268 |
Date Published | 2022 02 28 |
ISSN | 2045-2322 |
Keywords | Animals, Caenorhabditis elegans, Cholinergic Agents, Cholinergic Neurons, Disease Models, Animal, Dopamine, Parkinson Disease |
Abstract | <p>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.</p> |
DOI | 10.1038/s41598-022-07238-9 |
Alternate Journal | Sci Rep |
PubMed ID | 35228596 |
PubMed Central ID | PMC8885929 |
Grant List | U2CES030167 / / Office of Extramural Research, National Institutes of Health / R21HG011280Project / NH / NIH HHS / United States U24 DK097209 / DK / NIDDK NIH HHS / United States R03 CA222444 / CA / NCI NIH HHS / United States U2C ES030163 / ES / NIEHS NIH HHS / United States R01 ES023839 / ES / NIEHS NIH HHS / United States DP1 GM119167 / GM / NIGMS NIH HHS / United States F32 AG062036 / AG / NIA NIH HHS / United States |