| dc.contributor.author | Mucen Yu | |
| dc.contributor.author | Jielin Xu | |
| dc.contributor.author | Ranjan Dutta | |
| dc.contributor.author | Bruce Trapp | |
| dc.contributor.author | Andrew A. Pieper | |
| dc.contributor.author | Feixiong Cheng | |
| dc.contributor.other | Cleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic | |
| dc.contributor.other | Cleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic | |
| dc.contributor.other | Department of Neuroscience, Lerner Research Institute, Cleveland Clinic | |
| dc.contributor.other | Department of Neuroscience, Lerner Research Institute, Cleveland Clinic | |
| dc.contributor.other | Brain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland Medical Center | |
| dc.contributor.other | Cleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic | |
| dc.date.accessioned | 2024-11-10T12:31:07Z | |
| dc.date.available | 2025-10-02T05:21:36Z | |
| dc.date.issued | 01-11-2024 | |
| dc.identifier.issn | - | |
| dc.identifier.uri | https://doi.org/10.1038/s41540-024-00449-y | |
| dc.description.abstract | 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. | |
| dc.format | - | |
| dc.language.iso | EN | |
| dc.publisher | Nature Portfolio | |
| dc.relation.uri | ['https://www.cabidigitallibrary.org/journal/ab', 'https://www.cabidigitallibrary.org/journal/ab/aims-and-scope', 'https://www.cabidigitallibrary.org/journal/ab/submission-guidelines'] | |
| dc.rights | ['CC BY', 'CC0'] | |
| dc.subject | ['agriculture', 'food security', 'environment', 'plant science', 'animal science', 'agroecology', 'Agriculture (General)', 'S1-972'] | |
| dc.subject.lcc | Biology (General) | |
| dc.title | Network medicine informed multiomics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis | |
| dc.type | Article | |
| dc.description.pages | 1-9 | |
| dc.description.doi | 10.1038/s41540-024-00449-y | |
| dc.title.journal | npj Systems Biology and Applications | |
| dc.identifier.e-issn | 2056-7189 | |
| dc.identifier.oai | oai:doaj.org/journal:5c2c7a5d865c4837b4a0266377e13533 | |
| dc.journal.info | Volume 10, Issue 1 | |
