A Primer on Regression Methods for Decoding cis-Regulatory Logic 英文参考文献.docVIP

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A Primer on Regression Methods for Decoding cis-Regulatory Logic 英文参考文献.doc

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A Primer on Regression Methods for Decoding cis-Regulatory Logic 英文参考文献

Education APrimeronRegressionMethodsforDecodingcis- RegulatoryLogic DebopriyaDas1*,MatteoPellegrini2,JoeW.Gray1,3 1Life Sciences Division, Ernest O. Lawrence Berkeley National Laboratory, Berkeley, California, United States of America, 2Department of Molecular, Cell, and DevelopmentalBiology,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica,3ComprehensiveCancerCenter,UniversityofCaliforniaSan Francisco,SanFrancisco,California,UnitedStatesofAmerica Introduction Importanceofcis-Regulatory Elements expectedtranscriptionalresponseofgenes due to the binding of TFs to their promoters. While such methods have gathered popularity in the computational domain, they remain largely obscure to the broader biology community. The purpose of this tutorial is to bridge this gap. We will focus on transcriptional duce the regression method, let us first proceed by dividing the genes into two groups, according to whether a gene has thewordinitspromoterornot.Ifundera biological condition the expression levels of genes in these two groups are signifi- cantlydifferentfromeachother,itimplies thatthecis-elementismostlikelyboundby its cognate TF, which is regulating its target genes. In other words, the cis- element is active. However, if there is no significant difference in expression be- tweenthesetwogroups,then,analogously, the cis-element is likely inactive. Further- more, if the genes with the cis-motif have higher expression levels on average than thosewithoutthemotif,thentheTFisan activator, and in the reverse situation an inhibitor.ThecaseoftheMCBelement,a G1/Sregulatoroftheyeastcell-cycle[8], isillustratedinFigure1B.Weobservethat there is indeed a statistically significant association between the presence of the MCB element and mRNA expression in theG1/Sphaseofthecell-cycle(p,1.0e- 16),butnotintheG2/Mphase(p=0.02). Furthermore, this analysis indicates that theMCBelementhasanactivatingrolein theG1/Sphase,asexpected[8]. The rapidly emerging field o