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Wu WS and Li WH  (2008) Identifying gene regulatory modules of heat shock response in yeast. BMC Genomics 9:439

Abstract: ABSTRACT: BACKGROUND: A gene regulatory module (GRM) is a set of genes that is regulated by the same set of transcription factors (TFs). By organizing the genome into GRMs, a living cell can coordinate the activities of many genes in response to various internal and external stimuli. Therefore, identifying GRMs is helpful for understanding gene regulation. RESULTS: Integrating transcription factor binding site (TFBS), mutant, ChIP-chip, and heat shock time series gene expression data, we develop a method, called Heat-Inducible Module Identification Algorithm (HIMIA), for reconstructing GRMs of yeast heat shock response. Unlike previous module inference tools which are static statistics-based methods, HIMIA is a dynamic system model-based method that utilizes the dynamic nature of time series gene expression data. HIMIA identifies 29 GRMs, which in total contain 182 heat-inducible genes regulated by 12 heat-responsive TFs. Using various types of published data, we validate the biological relevance of the identified GRMs. Our analysis suggests that different combinations of a fairly small number of heat-responsive TFs regulate a large number of genes involved in heat shock response and that there may exist crosstalk between heat shock response and other cellular processes. Using HIMIA, we identify 68 uncharacterized genes that may be involved in heat shock response and we also identify their plausible heat-responsive regulators. Furthermore, HIMIA is capable of assigning the regulatory roles of the TFs that regulate GRMs and Cst6, Hsf1, Msn2, Msn4, and Yap1 are found to be activators of several GRMs. In addition, HIMIA refines two clusters of genes involved in heat shock response and provides a better understanding of how the complex expression program of heat shock response is regulated. Finally, we show that HIMIA outperforms four current module inference tools (GRAM, MOFA, ReMoDisvovery, and SAMBA), and we conduct two randomization tests to show that the output of HIMIA is statistically meaningful. CONCLUSIONS: HIMIA is effective for reconstructing GRMs of yeast heat shock response. Indeed, many of the reconstructed GRMs are in agreement with previous studies. Further, HIMIA predicts several interesting new modules and novel TF combinations. Our study shows that integrating multiple types of data is a powerful approach to studying complex biological systems.

Status: Published Type: Journal Article PubMed ID: 18811975

Topics addressed in this paper

Number of different genes curated to this paper: 192

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
ADD37 AFR1 AGX1 AHA1 AIM17 ALD4 ALG13 APE1 ARA1 ASI1
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Topics Genes linked to topics (#11 - 20 )
ATG12 ATG8 BAG7 BDH1 BXI1 CAD1 CHS3 CNL1 COA6 COQ6
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Topics Genes linked to topics (#21 - 30 )
COS5 COX20 CPR6 CRG1 CST6 CTL1 CTT1 CWP1 CYC7 DAK1
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Function/Process blue ball
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Topics Genes linked to topics (#31 - 40 )
DAP1 DDR48 DER1 DIG1 DOS2 ECI1 ECM38 ECM4 EMI1 ERO1
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Topics Genes linked to topics (#41 - 50 )
EUG1 FAA1 FAA4 FIS1 FLC2 FMP46 GAD1 GDH3 GFA1 GLK1
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Topics Genes linked to topics (#51 - 60 )
GLO1 GLO2 GLO4 GMC1 GOR1 GPH1 GRE3 GRX1 GSY2 GTT1
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Topics Genes linked to topics (#61 - 70 )
GUT2 HAC1 HBT1 HFD1 HKR1 HSF1 HSP10 HSP104 HSP12 HSP31
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Topics Genes linked to topics (#71 - 80 )
HSP60 HSP78 HXK1 HXT6 HXT7 IKS1 IRC24 ITC1 JEM1 KCH1
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Topics Genes linked to topics (#81 - 90 )
KEG1 KNS1 KTR2 LCB5 LHS1 LIN1 MAK32 MCD4 MGR1 MOH1
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Topics Genes linked to topics (#91 - 100 )
MPD1 MRPS16 MSC1 MSN2 MSN4 MSP1 MTD1 MTF2 NCA2 NCE103
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Function/Process blue ball blue ball
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Topics Genes linked to topics (#101 - 110 )
NTH1 PBI2 PCA1 PDE1 PDR15 PER33 PIR3 PNC1 PRM5 PRX1
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Regulation of 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 (#111 - 120 )
PST2 PTP2 PYC1 RBK1 RIM11 RIM20 RLM1 RNR3 ROX1 RPF1
Additional Literature blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Function/Process blue ball blue ball
Regulation of blue ball blue ball blue ball blue ball blue ball blue ball blue ball blue ball
Regulatory Role blue ball blue ball

Topics Genes linked to topics (#121 - 130 )
RRT8 RTC3 SCJ1 SCS3 SDS24 SEC1 SEC59 SFK1 SIL1 SLT2
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Topics Genes linked to topics (#131 - 140 )
SNZ1 SOH1 SPG3 SPG5 SPI1 SRL3 SSA1 SSA4 SSE2 STE12
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Function/Process blue ball
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Topics Genes linked to topics (#141 - 150 )
STF2 TES1 TKL2 TPS1 TSA2 TSL1 UBC8 UBI4 UBX3 UGA1
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Topics Genes linked to topics (#151 - 160 )
ULI1 UME6 YAP1 YAT1 YBL071C YBR056W YBR137W YBR139W YCL042W YDL057W
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Topics Genes linked to topics (#161 - 170 )
YDL073W YDL124W YER079W YET2 YGP1 YHR138C YIL108W YJL045W YJL068C YJR096W
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Topics Genes linked to topics (#171 - 180 )
YJR107W YKE2 YKE4 YKL091C YKL151C YLL056C YLL058W YLR050C YLR126C YLR345W
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Topics Genes linked to topics (#181 - 190 )
YMR090W YMR173W-A YNL155W YNL200C YOR052C YOR292C YPL071C YPL088W YRO2 YSC84
Additional Literature 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 (#191 - 192 )
YSP3 YTP1
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