Integration of screening and informatics is core to both target discovery and drug discovery in pharmaceutical research. My lab is involved in the creation and analysis of data generated by screening compounds, siRNA, shRNA, cDNA and CRISPR. These different but complementary approaches to interrogating biology are applied in a variety of disease-relevant phenotypic assays as well as large-scale cell profiling. Our goal is to make inferences about cellular pathways and networks dysregulated in disease by applying statistics and prior knowledge to screening data. Historically, my lab has united the disciplines of cheminformatics and bioinformatics to address problems such as compound target identification and prediction of drug side effects from chemical structure. We use large-scale correlations of compound features or compound bioactivity profiles to gain insight into compound mechanism-of-action, which leads to a better understanding of assay biology. More recently, we are mining genome-wide RNAi screening data to better understand perturbagen behavior, which has led to greater understanding about siRNA and miRNA cellular function. Additionally, by combining loss-of-function screening with cancer cell line genetic features, we are learning about synthetic lethal relationships that can be exploited for therapeutics. Finally, we apply large-scale knock-down screening to the problem of compound target identification in a lab setting where lab experimentalists and computational analysts work side-by-side. Quantifying epistasis between compounds and siRNA combinations will remain an active area of investigation.