Literature DB >> 24723613

Mapping the cellular response to small molecules using chemogenomic fitness signatures.

Anna Y Lee1, Robert P St Onge, Michael J Proctor, Iain M Wallace, Aaron H Nile, Paul A Spagnuolo, Yulia Jitkova, Marcela Gronda, Yan Wu, Moshe K Kim, Kahlin Cheung-Ong, Nikko P Torres, Eric D Spear, Mitchell K L Han, Ulrich Schlecht, Sundari Suresh, Geoffrey Duby, Lawrence E Heisler, Anuradha Surendra, Eula Fung, Malene L Urbanus, Marinella Gebbia, Elena Lissina, Molly Miranda, Jennifer H Chiang, Ana Maria Aparicio, Mahel Zeghouf, Ronald W Davis, Jacqueline Cherfils, Marc Boutry, Chris A Kaiser, Carolyn L Cummins, William S Trimble, Grant W Brown, Aaron D Schimmer, Vytas A Bankaitis, Corey Nislow, Gary D Bader, Guri Giaever.   

Abstract

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.

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Year:  2014        PMID: 24723613      PMCID: PMC4254748          DOI: 10.1126/science.1250217

Source DB:  PubMed          Journal:  Science        ISSN: 0036-8075            Impact factor:   47.728


  22 in total

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Authors:  Meredith M Rainey; Daniel Korostyshevsky; Sean Lee; Ethan O Perlstein
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2.  Discovery of drug mode of action and drug repositioning from transcriptional responses.

Authors:  Francesco Iorio; Roberta Bosotti; Emanuela Scacheri; Vincenzo Belcastro; Pratibha Mithbaokar; Rosa Ferriero; Loredana Murino; Roberto Tagliaferri; Nicola Brunetti-Pierri; Antonella Isacchi; Diego di Bernardo
Journal:  Proc Natl Acad Sci U S A       Date:  2010-08-02       Impact factor: 11.205

Review 3.  Drug-induced phospholipidosis.

Authors:  Nora Anderson; Jürgen Borlak
Journal:  FEBS Lett       Date:  2006-09-05       Impact factor: 4.124

4.  The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease.

Authors:  Justin Lamb; Emily D Crawford; David Peck; Joshua W Modell; Irene C Blat; Matthew J Wrobel; Jim Lerner; Jean-Philippe Brunet; Aravind Subramanian; Kenneth N Ross; Michael Reich; Haley Hieronymus; Guo Wei; Scott A Armstrong; Stephen J Haggarty; Paul A Clemons; Ru Wei; Steven A Carr; Eric S Lander; Todd R Golub
Journal:  Science       Date:  2006-09-29       Impact factor: 47.728

5.  The chemical genomic portrait of yeast: uncovering a phenotype for all genes.

Authors:  Maureen E Hillenmeyer; Eula Fung; Jan Wildenhain; Sarah E Pierce; Shawn Hoon; William Lee; Michael Proctor; Robert P St Onge; Mike Tyers; Daphne Koller; Russ B Altman; Ronald W Davis; Corey Nislow; Guri Giaever
Journal:  Science       Date:  2008-04-18       Impact factor: 47.728

6.  Compound prioritization methods increase rates of chemical probe discovery in model organisms.

Authors:  Iain M Wallace; Malene L Urbanus; Genna M Luciani; Andrew R Burns; Mitchell K L Han; Hao Wang; Kriti Arora; Lawrence E Heisler; Michael Proctor; Robert P St Onge; Terry Roemer; Peter J Roy; Carolyn L Cummins; Gary D Bader; Corey Nislow; Guri Giaever
Journal:  Chem Biol       Date:  2011-10-28

7.  Genomic profiling of drug sensitivities via induced haploinsufficiency.

Authors:  G Giaever; D D Shoemaker; T W Jones; H Liang; E A Winzeler; A Astromoff; R W Davis
Journal:  Nat Genet       Date:  1999-03       Impact factor: 38.330

8.  Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis.

Authors:  M Fang; B G Kearns; A Gedvilaite; S Kagiwada; M Kearns; M K Fung; V A Bankaitis
Journal:  EMBO J       Date:  1996-12-02       Impact factor: 11.598

9.  The genetic landscape of a cell.

Authors:  Michael Costanzo; Anastasia Baryshnikova; Jeremy Bellay; Yungil Kim; Eric D Spear; Carolyn S Sevier; Huiming Ding; Judice L Y Koh; Kiana Toufighi; Sara Mostafavi; Jeany Prinz; Robert P St Onge; Benjamin VanderSluis; Taras Makhnevych; Franco J Vizeacoumar; Solmaz Alizadeh; Sondra Bahr; Renee L Brost; Yiqun Chen; Murat Cokol; Raamesh Deshpande; Zhijian Li; Zhen-Yuan Lin; Wendy Liang; Michaela Marback; Jadine Paw; Bryan-Joseph San Luis; Ermira Shuteriqi; Amy Hin Yan Tong; Nydia van Dyk; Iain M Wallace; Joseph A Whitney; Matthew T Weirauch; Guoqing Zhong; Hongwei Zhu; Walid A Houry; Michael Brudno; Sasan Ragibizadeh; Balázs Papp; Csaba Pál; Frederick P Roth; Guri Giaever; Corey Nislow; Olga G Troyanskaya; Howard Bussey; Gary D Bader; Anne-Claude Gingras; Quaid D Morris; Philip M Kim; Chris A Kaiser; Chad L Myers; Brenda J Andrews; Charles Boone
Journal:  Science       Date:  2010-01-22       Impact factor: 47.728

10.  Forchlorfenuron alters mammalian septin assembly, organization, and dynamics.

Authors:  Qicong Hu; W James Nelson; Elias T Spiliotis
Journal:  J Biol Chem       Date:  2008-08-18       Impact factor: 5.157

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  106 in total

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Journal:  J Biol Chem       Date:  2018-12-04       Impact factor: 5.157

2.  Dark chemical matter as a promising starting point for drug lead discovery.

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Journal:  Nat Chem Biol       Date:  2015-10-19       Impact factor: 15.040

Review 3.  Functional genomics to uncover drug mechanism of action.

Authors:  Sebastian M B Nijman
Journal:  Nat Chem Biol       Date:  2015-11-17       Impact factor: 15.040

4.  Mitochondrial ClpX Activates a Key Enzyme for Heme Biosynthesis and Erythropoiesis.

Authors:  Julia R Kardon; Yvette Y Yien; Nicholas C Huston; Diana S Branco; Gordon J Hildick-Smith; Kyu Y Rhee; Barry H Paw; Tania A Baker
Journal:  Cell       Date:  2015-05-07       Impact factor: 41.582

5.  Structural elements that govern Sec14-like PITP sensitivities to potent small molecule inhibitors.

Authors:  Danish Khan; Kaitlyn R McGrath; Oleksandra Dorosheva; Vytas A Bankaitis; Ashutosh Tripathi
Journal:  J Lipid Res       Date:  2016-02-26       Impact factor: 5.922

Review 6.  Emerging and evolving concepts in gene essentiality.

Authors:  Giulia Rancati; Jason Moffat; Athanasios Typas; Norman Pavelka
Journal:  Nat Rev Genet       Date:  2017-10-16       Impact factor: 53.242

7.  MOSAIC: a chemical-genetic interaction data repository and web resource for exploring chemical modes of action.

Authors:  Justin Nelson; Scott W Simpkins; Hamid Safizadeh; Sheena C Li; Jeff S Piotrowski; Hiroyuki Hirano; Yoko Yashiroda; Hiroyuki Osada; Minoru Yoshida; Charles Boone; Chad L Myers
Journal:  Bioinformatics       Date:  2018-04-01       Impact factor: 6.937

8.  Target Identification and Mechanism of Action of Picolinamide and Benzamide Chemotypes with Antifungal Properties.

Authors:  Verena Pries; Christina Nöcker; Danish Khan; Philipp Johnen; Zebin Hong; Ashutosh Tripathi; Anna-Lena Keller; Michael Fitz; Francesca Perruccio; Ireos Filipuzzi; Sasikala Thavam; Thomas Aust; Ralph Riedl; Slava Ziegler; Fulvia Bono; Gabriel Schaaf; Vytas A Bankaitis; Herbert Waldmann; Dominic Hoepfner
Journal:  Cell Chem Biol       Date:  2018-01-04       Impact factor: 8.116

9.  Systematic Gene-to-Phenotype Arrays: A High-Throughput Technique for Molecular Phenotyping.

Authors:  Philipp A Jaeger; Lilia Ornelas; Cameron McElfresh; Lily R Wong; Randolph Y Hampton; Trey Ideker
Journal:  Mol Cell       Date:  2018-01-18       Impact factor: 17.970

10.  Derivatives of the Antimalarial Drug Mefloquine Are Broad-Spectrum Antifungal Molecules with Activity against Drug-Resistant Clinical Isolates.

Authors:  Marhiah C Montoya; Sarah Beattie; Kathryn M Alden; Damian J Krysan
Journal:  Antimicrob Agents Chemother       Date:  2020-02-21       Impact factor: 5.191

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