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| Prediction of mechanisms of action of antibacterial compounds by gene expression profiling |
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| Author(s): Hutter B, Schaab C, Albrecht S, Borgmann M, Brunner NA, Freiberg C, Ziegelbauer K, Rock CO, Ivanov I, Loferer H |
| Source: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Volume: 48 Issue: 8 Pages: 2838-2844 Published: AUG 2004 |
| Times Cited: 54 References: 34 |
| Abstract: We have generated a database of expression profiles carrying the transcriptional responses of the model organism Bacillus subtilis following treatment with 37 well-characterized antibacterial compounds of different classes. The database was used to build a predictor for the assignment of the mechanisms of action (MoAs) of antibacterial compounds by the use of support vector machines. This predictor was able to correctly classify the MoA class for most compounds tested. Furthermore, we provide evidence that the in vivo MoA of hexachlorophene does not match the MoA predicted from in vitro data, a situation frequently faced in drug discovery. A database of this kind may facilitate the prioritization of novel antibacterial entities in drug discovery programs. Potential applications and limitations are discussed. |
| Document Type: Article |
| Language: English |
| Reprint Address: Loferer, H (reprint author), GPC Biotech AG, Fraunhoferstr 20, D-8152 Munich, Germany |
Addresses:
1. GPC Biotech AG, D-8152 Munich, Germany 2. Bayer AG, Wuppertal, Germany 3. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA |
| Publisher: AMER SOC MICROBIOLOGY, 1752 N ST NW, WASHINGTON, DC 20036-2904 USA |
| Subject Category: Microbiology; Pharmacology & Pharmacy |
| IDS Number: 842IV |
| ISSN: 0066-4804 |
| DOI: 10.1128/AAC.48.8.2838-2844.2004 |
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