Network-assisted target identification for haploinsufficiency and homozygous profiling screens.
Chemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale. Drug target identification and elucidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain difficult. Here, we present GIT (Genetic Interaction N...
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Public Library of Science (PLoS)
2017-06-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005553&type=printable |
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| author | Sheng Wang Jian Peng |
| author_facet | Sheng Wang Jian Peng |
| author_sort | Sheng Wang |
| collection | DOAJ |
| description | Chemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale. Drug target identification and elucidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain difficult. Here, we present GIT (Genetic Interaction Network-Assisted Target Identification), a network analysis method for drug target identification in haploinsufficiency profiling (HIP) and homozygous profiling (HOP) screens. With the drug-induced phenotypic fitness defect of the deletion of a gene, GIT also incorporates the fitness defects of the gene's neighbors in the genetic interaction network. On three genome-scale yeast chemical genomic screens, GIT substantially outperforms previous scoring methods on target identification on HIP and HOP assays, respectively. Finally, we showed that by combining HIP and HOP assays, GIT further boosts target identification and reveals potential drug's mechanism of action. |
| format | Article |
| id | doaj-art-9f838babd1fc46e79703f6665c25faef |
| institution | Kabale University |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2017-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-9f838babd1fc46e79703f6665c25faef2025-01-24T05:30:55ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582017-06-01136e100555310.1371/journal.pcbi.1005553Network-assisted target identification for haploinsufficiency and homozygous profiling screens.Sheng WangJian PengChemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale. Drug target identification and elucidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain difficult. Here, we present GIT (Genetic Interaction Network-Assisted Target Identification), a network analysis method for drug target identification in haploinsufficiency profiling (HIP) and homozygous profiling (HOP) screens. With the drug-induced phenotypic fitness defect of the deletion of a gene, GIT also incorporates the fitness defects of the gene's neighbors in the genetic interaction network. On three genome-scale yeast chemical genomic screens, GIT substantially outperforms previous scoring methods on target identification on HIP and HOP assays, respectively. Finally, we showed that by combining HIP and HOP assays, GIT further boosts target identification and reveals potential drug's mechanism of action.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005553&type=printable |
| spellingShingle | Sheng Wang Jian Peng Network-assisted target identification for haploinsufficiency and homozygous profiling screens. PLoS Computational Biology |
| title | Network-assisted target identification for haploinsufficiency and homozygous profiling screens. |
| title_full | Network-assisted target identification for haploinsufficiency and homozygous profiling screens. |
| title_fullStr | Network-assisted target identification for haploinsufficiency and homozygous profiling screens. |
| title_full_unstemmed | Network-assisted target identification for haploinsufficiency and homozygous profiling screens. |
| title_short | Network-assisted target identification for haploinsufficiency and homozygous profiling screens. |
| title_sort | network assisted target identification for haploinsufficiency and homozygous profiling screens |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005553&type=printable |
| work_keys_str_mv | AT shengwang networkassistedtargetidentificationforhaploinsufficiencyandhomozygousprofilingscreens AT jianpeng networkassistedtargetidentificationforhaploinsufficiencyandhomozygousprofilingscreens |