A 2-sample variant of TELiS [63] identified upstream signal transduction pathways driving differential gene expression [41]. Primary analyses compared the prevalence of vertebrate V$GR_Q6 and V$CREL_01 TFBMs from the TRANSFAC database [64] in promoters of genes over-expressed in high- versus low-lonely individuals. Primary analyses utilized default scan parameters [41] and identified differences in TFBM prevalence using p values from an independent sample t-test with Welch's correction for heteroscedasticity [65]. To assess the robustness of results to technical variations, sensitivity analyses examined parametric variations of promoter length (-300 bp relative to RefSeq transcription start site, -600 bp, and -1,000 bp to +200), and motif match stringency (MatSim = 0.80, 0.90, 0.95) [41]. Sensitivity analyses also tested the impact of increasing stringency in the definition of differential gene expression (capture based on 1.5-fold change, corresponding to 5% FDR) [59].
