Structural alignment of pseudoknotted RNA

Authors:
Banu Dost;Buhm Han;Shaojie Zhang;Vineet Bafna
Affiliations:
Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA;Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA;Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA;Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA
Venue:
RECOMB'06 Proceedings of the 10th annual international conference on Research in Computational Molecular Biology
Year:
2006

Citing 7
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Abstract

In this paper, we address the problem of discovering novel non-coding RNA (ncRNA) using primary sequence, and secondary structure conservation, focusing on ncRNA families with pseudo-knotted structures. Our main technical result is an efficient algorithm for computing an optimum structural alignment of an RNA sequence against a genomic substring. This algorithm finds two applications. First, by scanning a genome, we can identify novel (homologous) pseudoknotted ncRNA, and second, we can infer the secondary structure of the target aligned sequence. We test an implementation of our algorithm (Pal), and show that it has near-perfect behavior for predicting the structure of many known pseudoknots. Additionally, it can detect the true homologs with high sensitivity and specificity in controlled tests. We also use Pal to search entire viral genome and mouse genome for novel homologs of some viral, and eukaryotic pseudoknots respectively. In each case, we have found strong support for novel homologs.