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Sample heterogeneity can have a considerable effect on transcription factor binding site detection. While manual separation techniques can be used to isolate a cell type of interest from heterogeneous samples, such techniques are challenging and can change intra-cellular interactions, including protein-DNA binding. Computational deconvolution methods have emerged as an alternative strategy to study heterogeneous samples and numerous methods have been proposed to analyze gene expression.
(Rautio and Lahdesmaki, 2015) MixChIP: a probabilistic method for cell type specific protein-DNA binding analysis. BMC Bioinformatics.