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Cell-Type-Specific Predictive Network Yields Novel Insights into Mouse Embryonic Stem Cell Self-Renewal and Cell Fate

Figure 6

Advantages of Statistically Principled Approach. A.

The iScMiD Core20 subnetwork of transcription factors used as bait in the 12 studies included in the iScMiD integrated mESC database [34], [35], recreated as an undirected graph using edges available from the iScMiD website. In the iScMiD network, all edges have equal weight and all high-throughput data is considered equally reliable, hence the authors note there may be many false positives. B. The fully connected clique of mESC network posteriors for the iScMiD Core20 transcription factors predicts connections not shown in iScMiD and reveals potential false positives as not all connections are equally supported by the evidential data. For comparison, we checked underlying data for two edges, highlighted in yellow, one of which is not supported in the iScMiD subnetwork (Suz12– Sox2), and one which is only weakly supported in our mESC-only network (Suz12– Myc). C. Contrasting detailed information about underlying data supporting the strong functional linkage between Suz12Sox2 (Edge Weight: 0.9998) versus the weak linkage between Suz12Myc (Edge Weight: 0.0007) shows that top supporting datasets vary from edge to edge and that the strength of dataset contribution to edge weight may differ significantly. (Highlighted rows are datasets that support both edges.).

Figure 6