Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling
A. Finding a network of interactions that link phosphorylation events and differentially transcribed genes can be formulated as an optimization problem on a protein interactome. The objective function (equation in box) represents a balance between excluding nodes for which there is experimental evidence (phosphorylated proteins as yellow circles and transcription factors as blue triangles) and including edges weighted by reliability. The light grey rectangle containing edges from transcription factors to target mRNAs indicates these edges are not directly included in the interactome. Instead, they are used to infer the activity of transcription factor candidates (see Materials and Methods). The optimal solution to the PCST problem connects the phoshoprotein termini and the transcription factor termini by reliable interactions (red lines) that may involve nodes not explicitly observed in the experimental data (Steiner nodes; dark grey circles). TF: transcription factor. DHS: differentially hypersensitive. DE: differential expression. The superscripts a to e correspond to the superscript labels of input data types in B. B. The input datasets from U87MG EGFRvIII-expressing cells used in this study.