The pathSCREENER is a genetically encoded screening assay and combines barcoded pathway activity assays with multiplexed genetic interference screening to deconvolute gene networks in mode-of-action studies.
For example, a neuronal activity reporter that expresses unique RNA molecular barcodes can be coupled to a pooled shRNA or sgRNA/CRISPRi library to identify targets, which modulate neuronal activity. In such a screening approach, inactivation of a positive modulator of activity-dependent neuronal signaling decreases the neuronal activity reporter (Fig. 1, center panel). By contrast, inactivation of a negative modulator of activity-dependent neuronal signaling increases the neuronal activity reporter (Fig. 1, right panel).
An example of Phenogenomic Target Deconvolution for complex brain disorders:
Applying the pathSCREENER assay allows identify novel targets and to deconvolute gene networks impacting on brain disorders (Fig. 2).