Fast and systematic genome-wide discovery of regulatory elements using network-level conservation

Olivier Elemento
Genomics Institute, Princeton University

I will describe a powerful alignment-free computational approach for discovering globally conserved regulatory elements between two genomes. The method works by scoring comprehensive lists of k-mers for network-level conservation. Using efficient string-matching algorithms, our implementation runs in time approximately proportional to the combined size of the genomes. Using this approach on the upstream regions (promoters) of yeast, worm, fly and mammalian genes, we obtained a large number of known and novel putative transcriptional regulatory elements. Many of these are validated by independent biological observations, have spatial and/or orientation biases, are co-conserved with other elements and show surprising conservation across large phylogenetic distances. We then applied the same approach to the 3'UTRs of worm and fly genes, in search for post-transcriptional regulatory elements. Surprisingly, many of the highly conserved elements we discovered are complementary to the 5' extremity of microRNAs. Finally, we found candidate novel microRNAs that may target the novel highly conserved sites our method discovered.

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