{"doi":"10.1038/s41540-024-00449-y","title":"Network medicine informed multiomics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis","abstract":null,"journal":"npj Systems Biology and Applications","year":2024,"id":613137,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":556876,"name":"Jielin Xu","orcid":null,"position":1,"is_corresponding":false},{"id":109686,"name":"Ranjan Dutta","orcid":"0000-0001-8502-4455","position":2,"is_corresponding":false},{"id":1579334,"name":"Bruce Trapp","orcid":null,"position":3,"is_corresponding":false},{"id":247916,"name":"Andrew A. Pieper","orcid":"0000-0001-6299-6577","position":4,"is_corresponding":false},{"id":69831,"name":"Feixiong Cheng","orcid":"0000-0002-1736-2847","position":5,"is_corresponding":false},{"id":1579333,"name":"Mucen Yu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Network medicine informed multiomics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis","abstract":"Amyotrophic Lateral Sclerosis (ALS) is a devastating, immensely complex neurodegenerative disease by lack of effective treatments. We developed a network medicine methodology via integrating human brain multi-omics data to prioritize drug targets and repurposable treatments for ALS. We leveraged non-coding ALS loci effects from genome-wide associated studies (GWAS) on human brain expression quantitative trait loci (QTL) (eQTL), protein QTL (pQTL), splicing QTL (sQTL), methylation QTL (meQTL), and histone acetylation QTL (haQTL). Using a network-based deep learning framework, we identified 105 putative ALS-associated genes enriched in known ALS pathobiological pathways. Applying network proximity analysis of predicted ALS-associated genes and drug-target networks under the human protein-protein interactome (PPI) model, we identified potential repurposable drugs (i.e., Diazoxide and Gefitinib) for ALS. Subsequent validation established preclinical evidence for top-prioritized drugs. In summary, we presented a network-based multi-omics framework to identify drug targets and repurposable treatments for ALS and other neurodegenerative disease if broadly applied.","is_dataset_classified":null,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39500920","pmcid":"PMC11538253","openalex_id":"https://openalex.org/W4404057823","authors":[],"funders":[{"funder_name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","grant_id":"U01AG073323","title":null},{"funder_name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","grant_id":"R01AG084250","title":null},{"funder_name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","grant_id":"R01AG066707","title":null},{"funder_name":"U.S. Department of Health & Human Services | NIH | National Institute 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