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Inference of molecular mechanisms of transcriptional regulation from co-expression data


 Co-expression analysis can be used to identify transcription factors and/or lncRNAs that directly regulate transcription of a gene. When all samples are in the same state, a transcription factor has to co-fluctuate with the target gene to be identifiable as regulatory. Co-fluctuation implies that a regulatory factor binds with intermediate strength. The binding is not too strong to make a factor constantly bound and not too weak to make a factor irrelevant. It follows that variables defining the binding of a factor are not all independent. For example, for transcription factors the following variables were suggested: expression level, binding strength and binding site accessibility. Any one of these variables can be made dependent. Relations between variable contain information about molecular mechanisms. This is true for regulatory lncRNAs as well. The significant difference is that the list of regulatory lncRNAs is unknown. Because of that, lncRNAs that were identified regulating transcription of a gene can only be compared to random lncRNAs. A method to distinguish regulatory lncRNAs by gene coverage was proposed.