Motivation: The biological significance of genomic features is often context dependent. Annotating a particular dataset with existing external data can provide insight into function.
Results: We present CruzDB, a fast and intuitive programmatic interface to the University of California, Santa Cruz (UCSC) genome browser that facilitates integrative analyses of diverse local and remotely hosted datasets. We showcase the syntax of CruzDB using microRNA binding sites as examples, and further demonstrate its utility with three biological discoveries. First, DNA replication timing is stratified in gene regions-exons tend to replicate early and introns late during S phase. Second, several non-coding variants associated with cognitive functions map to lincRNA transcripts of relevant function, suggesting potential function of these regulatory RNAs in neuronal diseases. Third, lamina-associated genomic regions are highly enriched in olfaction-related genes, indicating a role of nuclear organization in their regulation.