ABSTRACT
RESULTS: We have developed LeTICE (Learning Transcriptional networks from the Integration of ChIP-chip and Expression data), an algorithm for learning a transcriptional network from ChIP-chip and expression data. The network is specified by a binary matrix of transcription factor (TF)-gene interactions partitioning genes into modules and a background of genes that are not involved in the transcriptional regulation. We define a likelihood of a network, and then search for the network optimizing the likelihood. We applied LeTICE to the location and expression data from yeast cells grown in rich media to learn the transcriptional network specific to the yeast cell cycle. It found 12 condition-specific TFs and 15 modules each of which is highly represented with functions related to particular phases of cell-cycle regulation. AVAILABILITY: Our algorithm is available at http://linus.nci.nih.gov/Data/YounA/LeTICE.zip
Subject(s)
Algorithms , Computational Biology/methods , Gene Regulatory Networks , Cell Cycle/genetics , Cell Cycle/physiology , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Gene Expression Profiling , Gene Expression Regulation , Oligonucleotide Array Sequence Analysis , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Positron Emission Tomography was used to measure global and regional cardiac beta-adrenergic function in 19 normal subjects and 9 congestive heart failure patients. [(11)C]-meta-hydroxyephedrine was used to image norepinephrine transporter function as an indicator of pre-synaptic function and [(11)C]-CGP12177 was used to measure cell surface beta-receptor density as an indicator of post-synaptic function. Pre-synaptic, but not post-synaptic, function was significantly different between normals and CHF patients. Pre-synaptic function was well matched to post-synaptic function in the normal hearts but significantly different and poorly matched in the CHF patients studied. This imaging technique can help us understand regional sympathetic function in cardiac disease.
