Systems-level network modeling of Small Cell Lung Cancer subtypes identifies master regulators and destabilizers
Fig 6
Similar analysis in mouse tumors.
A. Ai. TKO (Rb1, Tp53, P130 floxed) mouse tumors showing a high proportion of NE and NEv2 subtypes. Aii. As described in [15], these mouse tumors were generated by crossing Rb1 fl/fl Trp53 fl/fl (RP) animals to knockin Lox-Stop-Lox (LSL)-MycT58A-IRES-Luciferase mice. These Rb1 fl/fl Trp53 fl/fl Myc LSL/LSL (RPM) mice have overexpressed Myc and have been shown to be driven towards a variant phenotype, which is corroborated in this CIBERSORT analysis. It is clear that RPM mice contain greater portions of NEv1 compared to the tumors in Ai., which seems to correspond to the Aurora-Kinase-inhibitor-sensitive, Myc-high phenotype published by Mollaoglu et al. B. t-SNE plots of single cell RNA-seq from two TKO mouse tumors. The k-nearest neighbors (kNN) with k = 10 was computed for each mouse cell to predict subtypes of individual cell using signature genes of each subtype. If at least 8 of the 10 nearest human cell line neighbors for a mouse cell were of one subtype, the cell was assigned that subtype. Large amounts of intratumoral and intertumoral heterogeneity are evident.