Inferring latent temporal progression and regulatory networks from cross-sectional transcriptomic data of cancer samples
Fig 4
Reconstructing EMT regulatory networks during bladder cancer progression.
(a) Expression patterns of the EMT regulatory genes along with the inferred latent-temporal progression of conventional urothelial carcinoma (UC) to aggressive sarcomatoid urothelial bladder cancer (SARC). (b) UC-specific network with edges unique to the UC network. (c) SARC-specific network with edges unique to the SARC network. Different colors of nodes in the network denote genes in different pathways (S1 Table). (d) Reconstructed expression dynamics of ACSS1, PTPN12 and CDH1. ACSS1 and PTPN12 have largest out-degree values in the UC-specific network and SARC-specific network, respectively. CDH1 is a marker gene of epithelial state during EMT. (e) A decrease in EMT score indicated a transition from epithelial to mesenchymal state during the progression of UC to SARC. The EMT score for each tumor sample was calculated as weighted sum of expression levels of 73 EMT-signature genes as introduced in [39]. Positive EMT score corresponds to the epithelial phenotype while negative score to mesenchymal phenotype. Wilcoxon rank sum test (one-tailed) p value was calculated to assess the statistical significance.