Finding recurrent RNA structural networks with fast maximal common subgraphs of edge-colored graphs

Abstract

MotivationsRNA tertiary structure is crucial to its many non-coding molecular functions. RNA architecture is shaped by its secondary structure composed of stems, stacked canonical base pairs, enclosing loops. While stems are captured by free-energy models, loops composed of non-canonical base pairs are not. Nor are distant interactions linking together those secondary structure elements (SSEs). Databases of conserved 3D geometries (a.k.a. modules) not captured by energetic models are lever-aged for structure prediction and design, but the computational complexity has limited their study to local elements, loops, and recently to those covering pairs of SSEs. Systematically capturing recurrent patterns on a large scale is a main challenge in the study of RNA structures. ResultsIn this paper, we present an efficient algorithm to compute maximal isomorphisms in edge colored graphs. This framework is well suited to RNA structures and allows us to generalize previous approaches. In particular, we apply our techniques to find for the first time modules spanning more than 2 SSEs, while improving speed a hundredfold. We extract all recurrent base pair networks among all non-redundant RNA tertiary structures and identify a module connecting 36 different SSEs common to the 23S ribosome of E. Coli and Thermus thermophilus. We organize this information as a hierarchy of modules sharing similarities in their structure, which can serve as a basis for future research on the emergence of structural patterns. Availabilityhttp://csb.cs.mcgill.ca/carnaval2