Abstract

Frequent subgraph mining is a useful method for extracting meaningful patterns from a set of graphs or a single large graph. Here, the graph represents all possible RNA structures and interactions. Patterns that are significantly more frequent in this graph over a random graph are extracted. We hypothesize that these patterns are most likely to represent biological mechanisms. The graph representation used is a directed dual graph, extended to handle intermolecular interactions. The graph is sampled for subgraphs, which are labeled using a canonical labeling method and counted. The resulting patterns are compared to those created from a randomized dataset and scored. The algorithm was applied to the mitochondrial genome of the kinetoplastid species Trypanosoma brucei, which has a unique RNA editing mechanism. The most significant patterns contain two stem-loops, indicative of gRNA, and represent interactions of these structures with target mRNA.

Highlights

  • In most organisms the process of protein synthesis is well understood

  • We presented a novel framework for the discovery of RNA elements. It is an adaptation of frequent subgraph mining techniques on a large directed dual graph, representing all possible complementary sequences

  • This is the first instance of dual graphs being used in this way and the first application of frequent subgraph mining for this problem

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Summary

Introduction

In most organisms the process of protein synthesis is well understood. Deoxyribonucleic acid (DNA) is transcribed into messenger ribonucleic acids (mRNA), which are translated into polypeptides that fold to create proteins. There are a few families of organisms where the process deviates from the norm. The mRNA produced from the mitochondrial DNA of this family cannot be directly translated into protein but must be prepared by a process called RNA editing. This process is mediated by short RNA molecules called guide RNA (gRNA) [1]. Another closely related family, Diplonema, has a unique editing system in its mitochondria. In this case the genes are fragmented into “modules” which are transcribed separately and assembled by an unknown mechanism [2]

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