Evidence map›Paper›PMID 39500920›Full record

ArticleNPJ systems biology and applications2024

Network medicine informed multiomics integration identifies drug targets and repurposable medicines for Amyotrophic Lateral Sclerosis.

Mucen Yu, Jielin Xu, Ranjan Dutta, Bruce Trapp, Andrew A Pieper, Feixiong Cheng

Abstract read
In one paragraph

Article in NPJ systems biology and applications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Mucen YuCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Jielin XuCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Ranjan DuttaDepartment of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Bruce TrappDepartment of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Andrew A PieperBrain Health Medicines Center, Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA.
Feixiong ChengCleveland Clinic Genome Center, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. chengf@ccf.org.ORCID 0000-0002-1736-2847

Funding

Endophenotype Network-based Approaches to Prediction and Population-based Validation of In Silico Drug Repurposing for Alzheimer's DiseaseR01AG066707 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng · 2020 to 2026
$4.9M
TREM2 Genotype-Informed Drug Repurposing and Combination Therapy Design for Alzheimer’s DiseaseR01AG076448 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng, Li Gan · 2022 to 2026
$4.0M
Alzheimer's MultiOme Data Repurposing: Artificial Intelligence, Network Medicine, and Therapeutics DiscoveryU01AG073323 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BEKRIS, LYNN, CHENG, FEIXIONG · 2021 to 2025
$4.0M
Alzheimer's Disease and Related Dementia-like Sequelae of SARS-CoV-2 Infection: Virus-Host Interactome, Neuropathobiology, and Drug RepurposingRF1AG082211 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI CHENG, FEIXIONG, PIEPER, ANDREW A · 2023 to 2023
$2.4M
Characterize neuronal and glial cell-specific vulnerability to proteinopathies in Alzheimer's disease using multimodal single-nuclei genomic and epigenomic approachesR01AG082118 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BONAKDARPOUR, BORNA, CHENG, FEIXIONG · 2023 to 2025
$2.4M
Dark GPCR signaling underlying the Microbiome-Gut-Brain Axis for Alzheimer's Disease and Related DementiaRF1NS133812 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI BROWN, JONATHAN MARK, CHENG, FEIXIONG · 2023 to 2023
$2.3M
Microglial Activation and Inflammatory Endophenotypes Underlying Sex Differences of Alzheimer’s DiseaseR01AG084250 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng, Justin D. Lathia · 2023 to 2026
$2.2M
Multimodal single-cell genomic and epigenomic analyses elucidate Alzheimer’s sexual dimorphism in human immune systems agingR56AG074001 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI BEKRIS, LYNN, CHENG, FEIXIONG · 2021 to 2021
$1.2M
Precision Medicine Digital Twins for Alzheimer’s Target and Drug Discovery and LongevityR21AG083003 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI CHENG, FEIXIONG · 2023 to 2023
$483k
NIA NIH HHS R01 AG066707NIA NIH HHS R01 AG076448NIA NIH HHS R01 AG082118NIA NIH HHS R01 AG084250NIA NIH HHS R21 AG083003NIA NIH HHS R56 AG074001NIA NIH HHS RF1 AG082211NIA NIH HHS U01 AG073323NINDS NIH HHS RF1 NS133812U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) RF1NS133812U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG066707U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG076448U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG082118U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG084250U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R21AG083003U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) RF1AG082211U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01AG073323
6 · The paper itself

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.

Indexed as

Amyotrophic Lateral SclerosisQuantitative Trait LociDrug RepositioningGenome-Wide Association StudyGenomicsHumansMultiomicsProtein Interaction Maps

Identifiers

PMID39500920
PMCPMC11538253

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.