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Parsons AB, et al.  (2004) Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways. Nat Biotechnol 22(1):62-9

Abstract: Bioactive compounds can be valuable research tools and drug leads, but it is often difficult to identify their mechanism of action or cellular target. Here we investigate the potential for integration of chemical-genetic and genetic interaction data to reveal information about the pathways and targets of inhibitory compounds. Taking advantage of the existing complete set of yeast haploid deletion mutants, we generated drug-hypersensitivity (chemical-genetic) profiles for 12 compounds. In addition to a set of compound-specific interactions, the chemical-genetic profiles identified a large group of genes required for multidrug resistance. In particular, yeast mutants lacking a functional vacuolar H(+)-ATPase show multidrug sensitivity, a phenomenon that may be conserved in mammalian cells. By filtering chemical-genetic profiles for the multidrug-resistant genes and then clustering the compound-specific profiles with a compendium of large-scale genetic interaction profiles, we were able to identify target pathways or proteins. This method thus provides a powerful means for inferring mechanism of action.

Status: Published Type: Journal Article PubMed ID: 14661025

Topics addressed in this paper

Number of different genes curated to this paper: 84

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
ARV1 BEM1 BEM2 BRE1 BRE2 BTS1 BUD25 CAX4 CHO2 CIK1
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Large-scale genetic interaction yg ball
Large-scale phenotype analysis yg ball
Omics yg ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball

Topics Genes linked to topics (#11 - 20 )
CIN1 CIN2 CIN4 CLB3 CNB1 CSF1 CUE1 DAP1 DCC1 DRS2
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball

Topics Genes linked to topics (#21 - 30 )
DYN1 DYN3 ELM1 ERG11 FKS1 GAS1 GET1 GET2 GIM4 GIM5
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#31 - 40 )
GRS1 GYP1 HCM1 JNM1 KEX2 KRE1 MAD2 MAD3 MCM21 MNN11
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball

Topics Genes linked to topics (#41 - 50 )
NPR2 OPI3 PAC2 PDR16 PMT2 RGP1 RIM20 RPN4 SAC1 SCS7
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball

Topics Genes linked to topics (#51 - 60 )
SLA1 SLT2 SMI1 SPF1 SSH1 SUM1 TUB2 UBC7 UBP6 UBX2
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
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Topics Genes linked to topics (#61 - 70 )
VAC14 VAN1 VMA10 VMA11 VMA16 VMA2 VMA21 VMA22 VMA3 VMA4
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball

Topics Genes linked to topics (#71 - 80 )
VMA5 VMA6 VMA7 VPH2 VPS1 VPS24 VPS29 VPS61 VPS63 YHR045W
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Strains/Constructs blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball

Topics Genes linked to topics (#81 - 84 )
YKL118W YPR089W YPT31 YPT6
Additional Literature blue ball blue ball blue ball
Genetic Interactions blue ball blue ball blue ball blue ball
Primary Literature blue ball
Strains/Constructs blue ball blue ball blue ball blue ball
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