Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures
Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogen...
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Veröffentlicht in: | Science (American Association for the Advancement of Science) 2014-04, Vol.344 (6180), p.208-211 |
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creator | Lee, Anna Y. St.Onge, Robert P. Proctor, Michael J. Wallace, Iain M. Nile, Aaron H. Spagnuolo, Paul A. Jitkova, Yulia Gronda, Marcela Wu, Yan Kim, Moshe K. Cheung-Ong, Kahlin Torres, Nikko P. Spear, Eric D. Han, Mitchell K. L. Schlecht, Ulrich Suresh, Sundari Duby, Geoffrey Heisler, Lawrence E. Surendra, Anuradha Fung, Eula Urbanus, Malene L. Gebbia, Marinella Lissina, Elena Miranda, Molly Chiang, Jennifer H. Aparicio, Ana Maria Zeghouf, Mahel Davis, Ronald W. Cherfils, Jacqueline Boutry, Marc Kaiser, Chris A. Cummins, Carolyn L. Trimble, William S. Brown, Grant W. Schimmer, Aaron D. Bankaitis, Vytas A. Nislow, Corey Bader, Gary D. Giaever, Guri |
description | Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes. |
doi_str_mv | 10.1126/science.1250217 |
format | Article |
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L. ; Schlecht, Ulrich ; Suresh, Sundari ; Duby, Geoffrey ; Heisler, Lawrence E. ; Surendra, Anuradha ; Fung, Eula ; Urbanus, Malene L. ; Gebbia, Marinella ; Lissina, Elena ; Miranda, Molly ; Chiang, Jennifer H. ; Aparicio, Ana Maria ; Zeghouf, Mahel ; Davis, Ronald W. ; Cherfils, Jacqueline ; Boutry, Marc ; Kaiser, Chris A. ; Cummins, Carolyn L. ; Trimble, William S. ; Brown, Grant W. ; Schimmer, Aaron D. ; Bankaitis, Vytas A. ; Nislow, Corey ; Bader, Gary D. ; Giaever, Guri</creator><creatorcontrib>Lee, Anna Y. ; St.Onge, Robert P. ; Proctor, Michael J. ; Wallace, Iain M. ; Nile, Aaron H. ; Spagnuolo, Paul A. ; Jitkova, Yulia ; Gronda, Marcela ; Wu, Yan ; Kim, Moshe K. ; Cheung-Ong, Kahlin ; Torres, Nikko P. ; Spear, Eric D. ; Han, Mitchell K. L. ; Schlecht, Ulrich ; Suresh, Sundari ; Duby, Geoffrey ; Heisler, Lawrence E. ; Surendra, Anuradha ; Fung, Eula ; Urbanus, Malene L. ; Gebbia, Marinella ; Lissina, Elena ; Miranda, Molly ; Chiang, Jennifer H. ; Aparicio, Ana Maria ; Zeghouf, Mahel ; Davis, Ronald W. ; Cherfils, Jacqueline ; Boutry, Marc ; Kaiser, Chris A. ; Cummins, Carolyn L. ; Trimble, William S. ; Brown, Grant W. ; Schimmer, Aaron D. ; Bankaitis, Vytas A. ; Nislow, Corey ; Bader, Gary D. ; Giaever, Guri</creatorcontrib><description>Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1250217</identifier><identifier>PMID: 24723613</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Biochemical mechanisms ; bioinformatics ; Biosynthesis ; Cell Line, Tumor ; Cells - drug effects ; Cellular biology ; chemical compounds ; Chemicals ; Drug Evaluation, Preclinical - methods ; Drug Resistance - genetics ; Exosomes ; Gene Regulatory Networks ; Genes ; Genetics ; Genome-Wide Association Study - methods ; Genomics ; Haploinsufficiency ; homozygosity ; Humans ; Molecules ; Pharmacogenetics ; physiology ; Proteins ; proteomics ; Saccharomyces cerevisiae - drug effects ; Saccharomyces cerevisiae - genetics ; Signatures ; Small Molecule Libraries - pharmacology ; Yeasts</subject><ispartof>Science (American Association for the Advancement of Science), 2014-04, Vol.344 (6180), p.208-211</ispartof><rights>Copyright © 2014 American Association for the Advancement of Science</rights><rights>Copyright © 2014, American Association for the Advancement of Science</rights><rights>Copyright 2014 by the American Association for the Advancement of Science; all rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c542t-7ef61d7e7e169e8680e455d5ef7870f335741a5c194cdc1c98a38df8153a514c3</citedby><cites>FETCH-LOGICAL-c542t-7ef61d7e7e169e8680e455d5ef7870f335741a5c194cdc1c98a38df8153a514c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24743624$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24743624$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24723613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Anna Y.</creatorcontrib><creatorcontrib>St.Onge, Robert P.</creatorcontrib><creatorcontrib>Proctor, Michael J.</creatorcontrib><creatorcontrib>Wallace, Iain M.</creatorcontrib><creatorcontrib>Nile, Aaron H.</creatorcontrib><creatorcontrib>Spagnuolo, Paul A.</creatorcontrib><creatorcontrib>Jitkova, Yulia</creatorcontrib><creatorcontrib>Gronda, Marcela</creatorcontrib><creatorcontrib>Wu, Yan</creatorcontrib><creatorcontrib>Kim, Moshe K.</creatorcontrib><creatorcontrib>Cheung-Ong, Kahlin</creatorcontrib><creatorcontrib>Torres, Nikko P.</creatorcontrib><creatorcontrib>Spear, Eric D.</creatorcontrib><creatorcontrib>Han, Mitchell K. L.</creatorcontrib><creatorcontrib>Schlecht, Ulrich</creatorcontrib><creatorcontrib>Suresh, Sundari</creatorcontrib><creatorcontrib>Duby, Geoffrey</creatorcontrib><creatorcontrib>Heisler, Lawrence E.</creatorcontrib><creatorcontrib>Surendra, Anuradha</creatorcontrib><creatorcontrib>Fung, Eula</creatorcontrib><creatorcontrib>Urbanus, Malene L.</creatorcontrib><creatorcontrib>Gebbia, Marinella</creatorcontrib><creatorcontrib>Lissina, Elena</creatorcontrib><creatorcontrib>Miranda, Molly</creatorcontrib><creatorcontrib>Chiang, Jennifer H.</creatorcontrib><creatorcontrib>Aparicio, Ana Maria</creatorcontrib><creatorcontrib>Zeghouf, Mahel</creatorcontrib><creatorcontrib>Davis, Ronald W.</creatorcontrib><creatorcontrib>Cherfils, Jacqueline</creatorcontrib><creatorcontrib>Boutry, Marc</creatorcontrib><creatorcontrib>Kaiser, Chris A.</creatorcontrib><creatorcontrib>Cummins, Carolyn L.</creatorcontrib><creatorcontrib>Trimble, William S.</creatorcontrib><creatorcontrib>Brown, Grant W.</creatorcontrib><creatorcontrib>Schimmer, Aaron D.</creatorcontrib><creatorcontrib>Bankaitis, Vytas A.</creatorcontrib><creatorcontrib>Nislow, Corey</creatorcontrib><creatorcontrib>Bader, Gary D.</creatorcontrib><creatorcontrib>Giaever, Guri</creatorcontrib><title>Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. 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ispartof | Science (American Association for the Advancement of Science), 2014-04, Vol.344 (6180), p.208-211 |
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language | eng |
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source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
subjects | Biochemical mechanisms bioinformatics Biosynthesis Cell Line, Tumor Cells - drug effects Cellular biology chemical compounds Chemicals Drug Evaluation, Preclinical - methods Drug Resistance - genetics Exosomes Gene Regulatory Networks Genes Genetics Genome-Wide Association Study - methods Genomics Haploinsufficiency homozygosity Humans Molecules Pharmacogenetics physiology Proteins proteomics Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - genetics Signatures Small Molecule Libraries - pharmacology Yeasts |
title | Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T12%3A35%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mapping%20the%20Cellular%20Response%20to%20Small%20Molecules%20Using%20Chemogenomic%20Fitness%20Signatures&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Lee,%20Anna%20Y.&rft.date=2014-04-11&rft.volume=344&rft.issue=6180&rft.spage=208&rft.epage=211&rft.pages=208-211&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.1250217&rft_dat=%3Cjstor_pubme%3E24743624%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1514780901&rft_id=info:pmid/24723613&rft_jstor_id=24743624&rfr_iscdi=true |