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
Hauptverfasser: 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
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container_end_page 211
container_issue 6180
container_start_page 208
container_title Science (American Association for the Advancement of Science)
container_volume 344
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
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1095-9203
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4254748
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