MSLN and cancer: This limitation precludes grouping by cell-intrinsic expression of genes of interest such as MSLN. To address this “chicken and egg” problem, we develop a histoepigenetic analysis method that expands on the EDec method in two ways: (1) It integrates within an iterative procedure a two-way clustering step with deconvolution to separate PDAC tumors based on cancer-cell-specific expression of a gene of interest such as MSLN; (2) It estimates a network of genes potentially interacting with the gene of interest.