Advancing our understanding of biological phenomena can be carried out through two complementary approaches: modeling and simulation of biological processes and bioinformatic analysis of genomic data. Modeling and simulation serves to provide tests of the plausibility and robustness of proposed biological mechanisms, and they can suggest previously unknown but experimentally testable hypotheses from known biological interactions. Bioinformatic analysis strives to discover meaningful patterns from genomic and other data that serve as hypotheses about the structure and function of genome features and their relationship among organisms. This dissertation addresses the challenge of both approaches through modeling and simulation of limb chondrogenesis and novel algorithms and computational tools for multiple organism comparative genomics.