v-jun avian sarcoma virus 17 oncogene homolog / Jun proto-oncogene, AP-1 transcription factor subunit (JUN) : Time behavioural study of 3rd order combinations in WNT3A stimulated HEK 293 cells

JUN encode the transcription factor Jun. The structure of activator protein (AP1) is a heterodimer composed of proteins belonging to the c-FOS, c-JUN, ATF and JDP families. Both JUN and its heterodimerization partners in AP1 formation, are subject to regulation by diverse extracellular stimuli, like peptide growth factors, pro-inflammatory cytokines, oxidative and other forms of cellular stress, and UV irradiation. 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 of- ten 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 JUN related 3rd order combinations in a forest of 71C3 combinations using four different sensitivity methods; • show the conserved rankings for JUN-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.