Evidence mapPaperPMID 36594024Full record

ArticleiScience2023

Synthesize heterogeneous biological knowledge via representation learning for Alzheimer's disease drug repurposing.

Kang-Lin Hsieh, German Plascencia-Villa, Ko-Hong Lin, George Perry, Xiaoqian Jiang, Yejin Kim

Open access · goldAbstract read
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
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

8 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. DALK: Dynamic Co-Augmentation of LLMs and KG to answer Alzheimer's Disease Questions with Scientific Literature.Findings of ACL. EMNLP. Conference on Empirical Methods in Natural Language Processing · 2024
    Article
  7. Article
  8. Integrating Comorbidity Knowledge for Alzheimer's Disease Drug Repurposing using Multi-task Graph Neural Network.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Kang-Lin HsiehCenter for Secure Artificial Intelligence for Healthcare, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
German Plascencia-VillaDepartment of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, TX 78729, USA.
Ko-Hong LinCenter for Secure Artificial Intelligence for Healthcare, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
George PerryDepartment of Neuroscience, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, TX 78729, USA.
Xiaoqian JiangCenter for Secure Artificial Intelligence for Healthcare, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Yejin KimCenter for Secure Artificial Intelligence for Healthcare, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
The University of Texas Health Science Center at Houston · USThe University of Texas at San Antonio · US

Funding

NIA NIH HHS R01 AG066749
6 · The paper itself

Abstract

Developing drugs for treating Alzheimer's disease has been extremely challenging and costly due to limited knowledge of underlying mechanisms and therapeutic targets. To address the challenge in AD drug development, we developed a multi-task deep learning pipeline that learns biological interactions and AD risk genes, then utilizes multi-level evidence on drug efficacy to identify repurposable drug candidates. Using the embedding derived from the model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, efficacy in preclinical models, population-based treatment effects, and clinical trials. We mechanistically validated the top-ranked candidates in neuronal cells, identifying drug combinations with efficacy in reducing oxidative stress and safety in maintaining neuronal viability and morphology. Our neuronal response experiments confirmed several biologically efficacious drug combinations. This pipeline showed that harmonizing heterogeneous and complementary data/knowledge, including human interactome, transcriptome patterns, experimental efficacy, and real-world patient data shed light on the drug development of complex diseases.

Indexed as

Artificial intelligenceDrugsNeuroscience

Identifiers

PMID36594024
PMCPMC9804117
OpenAlexW4310136297

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.