Large-scale molecular data has revolutionized the field of biology. However,such data come with considerable challenges in experimental design, computational modeling, and interpretation. Here I present three papers which take advantage of large-scale molecular data and advance the statistical methods for identifying biologically relevant features. The first paper relates epistatic interactions identified using gene knockouts to those identified using naturally occurring genetic variants. These interactions are further integrated with physical interaction data to produce a functional cellular map of yeast. The second paper implements genetic and physical interaction alignment in a user-friendly and interactive software package. The third paper investigates the effect of aging on the human methylome. Together, these works represent my principal contribution to the biological community to date and form the basis of my dissertation