Genome-wide transcriptional analysis provides a comprehensive molecular representation of cellular activity, suggesting that mRNA expression profiling could serve as a practical universal functional bioassay. High-throughput gene-expression profiling solutions raise the possibility of capturing the consequences of small-molecule and genetic perturbations at library scale, and associating these disparate perturbagens with each other and external organic phenotypes to discover decisive functional connections between drugs, genes and diseases. The talk will describe our technology platform, analysis methods and interpretive tools, and illustrate how the expression profiles of a large collection of bioactive small molecules can be used to reveal mechanisms of action of novel compounds, annotate complex phenotypes, and identify potential therapeutics. Exposing our data and search algorithms to the global biomedical-research community through a freely-accessible self-service webtool has also demonstrated the principle and value of digitizing, distributing, and democratizing the small-molecule screening process. The idea that a comparable system populated with expression profiles of a pharmaceutical company’s proprietary small-molecule library could serve as an efficient open-innovation platform will be discussed.