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Preclinical validation of therapeutic targets predicted by tensor factorization on heterogeneous graphs
- Source :
- Scientific Reports, Vol 10, Iss 1, Pp 1-19 (2020), Scientific Reports
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- Incorrect drug target identification is a major obstacle in drug discovery. Only 15% of drugs advance from Phase II to approval, with ineffective targets accounting for over 50% of these failures1–3. Advances in data fusion and computational modeling have independently progressed towards addressing this issue. Here, we capitalize on both these approaches with Rosalind, a comprehensive gene prioritization method that combines heterogeneous knowledge graph construction with relational inference via tensor factorization to accurately predict disease-gene links. Rosalind demonstrates an increase in performance of 18%-50% over five comparable state-of-the-art algorithms. On historical data, Rosalind prospectively identifies 1 in 4 therapeutic relationships eventually proven true. Beyond efficacy, Rosalind is able to accurately predict clinical trial successes (75% recall at rank 200) and distinguish likely failures (74% recall at rank 200). Lastly, Rosalind predictions were experimentally tested in a patient-derived in-vitro assay for Rheumatoid arthritis (RA), which yielded 5 promising genes, one of which is unexplored in RA.
- Subjects :
- Computer science
Drug target
Drug Evaluation, Preclinical
Inference
lcsh:Medicine
Machine learning
computer.software_genre
Article
Arthritis, Rheumatoid
Bayes' theorem
Drug Development
Target identification
Drug Discovery
Computer Graphics
Humans
Computer Simulation
lcsh:Science
Gene
Multidisciplinary
business.industry
Drug discovery
Rank (computer programming)
lcsh:R
Computational Biology
Bayes Theorem
Clinical trial
Identification (information)
Data integration
lcsh:Q
Artificial intelligence
business
computer
Algorithms
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....dc3bc291fac20ad8e1e0ef7a152b79aa