Identification of small molecule aggregators from large compound libraries by support vector machines
(c) 2009 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 31(2010), 4 vom: 01. März, Seite 752-63 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2010
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Small Molecule Libraries |
| Zusammenfassung: | (c) 2009 Wiley Periodicals, Inc. Small molecule aggregators non-specifically inhibit multiple unrelated proteins, rendering them therapeutically useless. They frequently appear as false hits and thus need to be eliminated in high-throughput screening campaigns. Computational methods have been explored for identifying aggregators, which have not been tested in screening large compound libraries. We used 1319 aggregators and 128,325 non-aggregators to develop a support vector machines (SVM) aggregator identification model, which was tested by four methods. The first is five fold cross-validation, which showed comparable aggregator and significantly improved non-aggregator identification rates against earlier studies. The second is the independent test of 17 aggregators discovered independently from the training aggregators, 71% of which were correctly identified. The third is retrospective screening of 13M PUBCHEM and 168K MDDR compounds, which predicted 97.9% and 98.7% of the PUBCHEM and MDDR compounds as non-aggregators. The fourth is retrospective screening of 5527 MDDR compounds similar to the known aggregators, 1.14% of which were predicted as aggregators. SVM showed slightly better overall performance against two other machine learning methods based on five fold cross-validation studies of the same settings. Molecular features of aggregation, extracted by a feature selection method, are consistent with published profiles. SVM showed substantial capability in identifying aggregators from large libraries at low false-hit rates |
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| Beschreibung: | Date Completed 16.04.2010 Date Revised 03.02.2010 published: Print Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.21347 |