Open AccessChemogenomic profiling predicts antifungal synergies
Author(s) -
Jansen Gregor,
Lee Anna Y,
Epp Elias,
Fredette Amélie,
Surprenant Jamie,
Harcus Doreen,
Scott Michelle,
Tan Elaine,
Nishimura Tamiko,
Whiteway Malcolm,
Hallett Michael,
Thomas David Y
Publication year - 2009
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2009.95
Subject(s) - biology , profiling (computer programming) , computational biology , antifungal , bioinformatics , microbiology and biotechnology , computer science , operating system
Chemotherapies, HIV infections, and treatments to block organ transplant rejection are creating a population of immunocompromised individuals at serious risk of systemic fungal infections. Since single‐agent therapies are susceptible to failure due to either inherent or acquired resistance, alternative therapeutic approaches such as multi‐agent therapies are needed. We have developed a bioinformatics‐driven approach that efficiently predicts compound synergy for such combinatorial therapies. The approach uses chemogenomic profiles in order to identify compound profiles that have a statistically significant degree of similarity to a fluconazole profile. The compounds identified were then experimentally verified to be synergistic with fluconazole and with each other, in both Saccharomyces cerevisiae and the fungal pathogen Candida albicans. Our method is therefore capable of accurately predicting compound synergy to aid the development of combinatorial antifungal therapies.