RECeSS · Robust Explainable Controllable Standard for drug Screening
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2023-05-01 → 2025-04-30
- EU contribution
- €189,687
- Participants
- 2
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Robust Explainable Controllable Standard for drug Screening
Drug development pipelines follow a stringent, costly, and time-consuming process to ensure patients’ safety. In 2024, those pipelines lasted 10 to 15 years, and the cost of their different steps, from drug (re)discovery to clinical trials, amounted to 500 million to 2 billion euros. Despite the significant resources spent during development, almost 24% of late-stage drug candidates could not obtain marketing authorization from the European Medicine Agency between 2013 and 2021. Most of the reported reasons for failure of marketization are related to late detection of toxic side effects or low evidence for efficacy compared to the standard-of-care treatment. Compared to the increasing cost of pipelines, the high failure rate exerts considerable pressure upon patients, healthcare services, and pharma companies, especially those related to rare or neglected tropical diseases, for which funds or data might be insufficient. Drug repurposing, or repositioning, is a strategy to overcome some of the difficulties in in novo pipelines by focusing the drug discovery efforts on already available chemical compounds (for instance, therapeutic drugs or tool molecules). However, drug repurposing proves to be challenging in the face of a lack of information about drug-disease indications and noisy, high-dimensional, and missing biological data. The RECeSS project is a transnational project between Germany and France, gathering machine learning and systems biology experts to implement drug repurposing for real-life resources. We aspire to provide an end-to-end approach to drug repurposing, from data collection and analysis across multiple diseases and candidate treatments to the risk-aware prediction of promising drug candidates.
Data: CORDIS, © European Union
Project objective
In 2021, drug development pipelines last 10 years in average, and cost around $2 billion, while facing high failure rates, as only around 10% of Phase 0 drug candidates reach the commercialization stage. These issues can be mitigated through drug repurposing, where existent compounds are systematically screened for new therapeutic indications. Collaborative filtering is a semi-supervised learning framework that leverages known drug-disease matchings to make novel recommendations. However, prior works cannot be leveraged because of their lack of focus on human oversight and robustness to biological data.This project aims at bridging the gap between drug research and collaborative filtering by implementing a RECeSS classifier, that is (1) Robust: deals with class imbalance in drug-disease matchings, and missing drug/disease features, by semi-supervised learning;(2) Explainable: connects predicted matchings to perturbed biological pathways through enrichment analyses, based on the learnt importance of features in the model;(3) Controllable: guarantees a bound on the false positive rate using an adaptive learning scheme;(4) Standard: algorithms are trained and tested by a standardized open-source pipeline.Predicted matchings will be independently validated by structure-based methods. This innovative interdisciplinary project relies on a solid basis of newly curated data (up to 1,386 drugs, 1,599 diseases, 12 feature types). It is primarily supervised by Pr. Olaf Wolkenhauer, at SBI Rostock, whose team has an expertise in drug repurposing, in systems biology and data imbalance in machine learning. This project will help the fellow develop new skills, and enhance her professional maturity in academia.In the short term, this would yield the first method that fully integrates biological interpretation and risk assessment to collaborative filtering-based repurposing. Long-term outcomes might help define sustainable and transparent drug development for rare diseases.
Original text from CORDIS.
Participants
Links
- View on CORDIS
- DOI: 10.3030/101102016
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e516e72922&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5fd6ee91d&appId=PPGMS
Data: CORDIS, © European Union