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Chunk #102 — Online Methods — 11. Predicting regulators active in each tissue / cell type / lineage

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Integrative analysis of 111 reference human epigenomes.
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We compute an expression score for each enhancer module and transcription factor as the Pearson correlation between the TF expression across cell types with expression data (quantile-normalized log(RPKM) with zeros replaced by log(0.0005)) and the ‘center’ of a module. For each enhancer module, its center is defined as a vector of length 111, containing the fraction of regions in that module called as (any type of) enhancer in each of the 111 epigenomes analyzed. This expression score is meant to act as the “expression” of a transcription factor within a module of cell types. We then compute an expression-enrichment value for each transcription factor as the correlation of this expression score and the enrichment of the corresponding motif across enhancer modules. The top 40 motifs in terms of their absolute expression-enrichment correlation and the clusters with log2 enrichment or depletion of at least log2=1.5 for at least one motif are shown in Fig. 8 and Extended Data 8a (only one motif is shown in Fig. 8 for each factor).