WNT-1/2B/3A/4/5A : Time Behavioural Study of 3rd Order Combinations in WNT3A Stimulated HEK 293 Cells

The WNT proteins are a family of a number of cysteine-rich glycoproteins which activate signal transduction cascades via three different pathways, the canonical WNT pathway, the noncanonical planar cell polarity (PCP) pathway, and the noncanonical WNT/Ca2+ pathway. Here, a time behavioural study of 3rd order WNT combinations in WNT3A stimulated HEK 293 cells is presented. Gujral and MacBeath [1] provides a quantitative, and dynamic study of WNT3A-mediated stimulation of HEK 293 cells, where they record time based expression profiles of several response genes which correlated significantly with proliferation and migration. By monitoring the dynamics of gene expression using self-organizing maps, they identified clusters of genes that exhibit similar expression dynamics and uncovered previously unrecognized positive and negative feedback loops. However, their study depicts/uses singular measurements of individual gene expression at different time snapshots/points to infer the system wide analysis of the pathway. At any particular time point, it is often the case that genes are working synergistically in combinations, even though their expression measurements are singular in nature. Here, I • enumerate and rank all 2415 WNT (particular family member) related 3rd order combinations in a forest of 71C3 combinations using four different sensitivity methods; • show the conserved rankings for WNT-X-X combinations, which point to existence of biological synergy of some of these combinations across the different sensitivity methods; and • study the behaviour of some of these combinations related to WNT3A response genes that are ranked by the machine learning search engine (Sinha [2]) in time. Patterns of combinations emerge, some of which have been tested in wet lab, while others require further wet lab analysis.