Machine learning-powered antibiotics phenotypic drug discovery
| Autor: | Roland Schmucki, Asha Ivy Jacob, Fethallah Benmansour, Christian Lerner, Andrea Araujo Del Rosario, Tobias Heckel, Andreas Maunz, Clive S. Mason, Luise Wolf, Marco Prunotto, Sannah Jensen Zoffmann, Michael Prummer, Hoa Hue Truong, Mark Burcin, Haiyuan Ding, Rita Blum Marti, Kenneth Bradley, Maarten Vercruysse, Kurt Amrein |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.drug_class Computer science Chemical structure Antibiotics Drug Evaluation Preclinical lcsh:Medicine Machine learning computer.software_genre Article Machine Learning 03 medical and health sciences 0302 clinical medicine Drug Discovery High-Throughput Screening Assays medicine Humans Potency lcsh:Science Multidisciplinary Bacteria business.industry Drug discovery lcsh:R Chemical space Anti-Bacterial Agents 030104 developmental biology High-content screening Classical pharmacology lcsh:Q Artificial intelligence business computer 030217 neurology & neurosurgery Primary screening |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019) Scientific Reports, 9 (1) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-39387-9 |
| Popis: | Identification of novel antibiotics remains a major challenge for drug discovery. The present study explores use of phenotypic readouts beyond classical antibacterial growth inhibition adopting a combined multiparametric high content screening and genomic approach. Deployment of the semi-automated bacterial phenotypic fingerprint (BPF) profiling platform in conjunction with a machine learning-powered dataset analysis, effectively allowed us to narrow down, compare and predict compound mode of action (MoA). The method identifies weak antibacterial hits allowing full exploitation of low potency hits frequently discovered by routine antibacterial screening. We demonstrate that BPF classification tool can be successfully used to guide chemical structure activity relationship optimization, enabling antibiotic development and that this approach can be fruitfully applied across species. The BPF classification tool could be potentially applied in primary screening, effectively enabling identification of novel antibacterial compound hits and differentiating their MoA, hence widening the known antibacterial chemical space of existing pharmaceutical compound libraries. More generally, beyond the specific objective of the present work, the proposed approach could be profitably applied to a broader range of diseases amenable to phenotypic drug discovery. Scientific Reports, 9 (1) ISSN:2045-2322 |
| Databáze: | OpenAIRE |
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