Fig. 6

Network analysis using key molecules in VL pathogenesis. We prioritized five DEGs (STAT1, MYC, PRKCD, PTPN6, and FGFR2) based on combined transcriptional- (VL-blood and skin) as well as in silico bioinformatics-based analyses. These 5 molecules/proteins were used as seed nodes to construct a network using the shortest path algorithm with a 2-step connection. Proteins are ordered according to their cellular localization from left to right. All five prioritized molecules are reaction hubs (blue ovals) where curated interactions are observed with both positive (green lines) and negative effects (red lines) directly to and from (direction of arrow) the hubs with several objects in the VL-blood profile as well as the larger human proteome database. (a) Portions of several canonical pathways are included in the network (in cyan), (b) a few canonical pathway portions have been traced including PTPN6-MYC-ELK1, Collagen 1-alpha11/beta1integrin-MYC, PTPN6-JAK2-BCL2 (in magenta) that are involved in immune regulation and inflammation and others such as CASP8-Cytochrome c-CASP9, Apo2L-DR5-BAX (in orange), are associated with apoptosis and survival. Gene expression data from both VL-blood and skin profiles are overlaid on the same network. The up- and down-stream interactions revealed by our network analyses may be leveraged to assess and validate functional consequences of targeting the 5 molecules by therapeutic drugs in future investigations. See Fig. 4 for legend