After DNA damage, cells can either proliferate, undergo cell death, or enter a senescent state. Multiple survival and stress signaling pathways need to integrate information at the single-cell level to choose amongst these phenotypic outcomes. Here I present data implicating multiple MAP Kinase pathways as modulators of cell fate, and discuss the development of a multi-omics experimental and computational approach to better understand potential signaling mechanisms that differentiate cell fates under heterogeneous contexts.

Tiling screens using CRISPR-Cas technologies provide a powerful approach to map regulatory elements to phenotypes of interest. Here we present CRISPR-SURF, a deconvolution framework to identify functional regulatory regions in the genome from data generated by CRISPR-Cas nuclease, CRISPR interference (CRISPRi), or CRISPR activation (CRISPRa) tiling screens. We validated CRISPR-SURF on previously published and new data, identifying both experimentally validated and new potential regulatory elements.