Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action
Abstract We present a cross‐species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug score...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-12-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb.2010.107 |
| _version_ | 1826990429867868160 |
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| author | Laura Kapitzky Pedro Beltrao Theresa J Berens Nadine Gassner Chunshui Zhou Arthur Wüster Julie Wu M Madan Babu Stephen J Elledge David Toczyski R Scott Lokey Nevan J Krogan |
| author_facet | Laura Kapitzky Pedro Beltrao Theresa J Berens Nadine Gassner Chunshui Zhou Arthur Wüster Julie Wu M Madan Babu Stephen J Elledge David Toczyski R Scott Lokey Nevan J Krogan |
| author_sort | Laura Kapitzky |
| collection | DOAJ |
| description | Abstract We present a cross‐species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug scores (or D‐scores), identifying mutants that are either sensitive or resistant to particular compounds. We found that compound–functional module relationships are more conserved than individual compound–gene interactions between these two species. Furthermore, we observed that combining data from both species allows for more accurate prediction of MoA. Finally, using this platform, we identified a novel small molecule that acts as a DNA damaging agent and demonstrate that its MoA is conserved in human cells. |
| first_indexed | 2024-03-07T16:44:59Z |
| format | Article |
| id | doaj.art-2f5a0ad2ef864d9bbc46df89f6b00810 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2025-02-18T08:20:24Z |
| publishDate | 2010-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-2f5a0ad2ef864d9bbc46df89f6b008102024-11-03T12:54:53ZengSpringer NatureMolecular Systems Biology1744-42922010-12-016111310.1038/msb.2010.107Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of actionLaura Kapitzky0Pedro Beltrao1Theresa J Berens2Nadine Gassner3Chunshui Zhou4Arthur Wüster5Julie Wu6M Madan Babu7Stephen J Elledge8David Toczyski9R Scott Lokey10Nevan J Krogan11Department of Cellular and Molecular Pharmacology, QB3 Institute, University of CaliforniaDepartment of Cellular and Molecular Pharmacology, QB3 Institute, University of CaliforniaDepartment of Biochemistry and Biophysics, Cancer Research Institute, University of CaliforniaUCSC Chemical Screening Center, University of CaliforniaDepartment of Genetics, Harvard University Medical School, and Division of Genetics, Howard Hughes Medical Institute, Brigham and Women's HospitalDepartment of Cellular and Molecular Pharmacology, QB3 Institute, University of CaliforniaDepartment of Cellular and Molecular Pharmacology, QB3 Institute, University of CaliforniaMRC Laboratory of Molecular BiologyDepartment of Genetics, Harvard University Medical School, and Division of Genetics, Howard Hughes Medical Institute, Brigham and Women's HospitalDepartment of Biochemistry and Biophysics, Cancer Research Institute, University of CaliforniaUCSC Chemical Screening Center, University of CaliforniaDepartment of Cellular and Molecular Pharmacology, QB3 Institute, University of CaliforniaAbstract We present a cross‐species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug scores (or D‐scores), identifying mutants that are either sensitive or resistant to particular compounds. We found that compound–functional module relationships are more conserved than individual compound–gene interactions between these two species. Furthermore, we observed that combining data from both species allows for more accurate prediction of MoA. Finally, using this platform, we identified a novel small molecule that acts as a DNA damaging agent and demonstrate that its MoA is conserved in human cells.https://doi.org/10.1038/msb.2010.107chemogenomicsevolutionmodularity |
| spellingShingle | Laura Kapitzky Pedro Beltrao Theresa J Berens Nadine Gassner Chunshui Zhou Arthur Wüster Julie Wu M Madan Babu Stephen J Elledge David Toczyski R Scott Lokey Nevan J Krogan Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action Molecular Systems Biology chemogenomics evolution modularity |
| title | Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action |
| title_full | Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action |
| title_fullStr | Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action |
| title_full_unstemmed | Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action |
| title_short | Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action |
| title_sort | cross species chemogenomic profiling reveals evolutionarily conserved drug mode of action |
| topic | chemogenomics evolution modularity |
| url | https://doi.org/10.1038/msb.2010.107 |
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