Biology has traditionally been a low-throughput science, where gleaning insights into processes has been slow and expensive. However, with advances in DNA synthesis and sequencing, as well as high-content imaging, biology is quickly becoming a data-driven discipline, in which thousands of biological hypotheses can be answered in a single test tube. I will first highlight the technologies that have enabled this revolution. I will then discuss these advances in the context of understanding natural genetic variation with computational models and their application in predicting the effects of mutations and designing new sets of sequences with desirable properties.