A program to automate the comparative analysis of RNA secondary structure

Roderic D. M. Page (

What is it? Circles is an experimental Windows 95/98/NT program for inferring RNA secondary structure using the comparative method. It provides a user-friendly interface to Jack Tabaska's maximum weight matching programs. The user can read in an alignment in FASTA, Clustal, or NEXUS format, compute a maximum weight matching, and export one or more secondary structures in standard formats.

Availability and requirements


Circles is available here as a self extracting executable file for Windows 95/98/NT.

Click on the icon to download your copy.

Release history 15 May 2000 Version 0.1.0
First release.

Documentation An online manual is available here.

Motivation Comparative analysis is the preferred method of inferring RNA secondary structure, but its use requires considerable expertise and manual effort. As the importance of secondary structure for accurate sequence alignment and phylogenetic analysis becomes increasingly realised, the need for secondary structure models for diverse taxonomic groups becomes more pressing. Maximum weight matching (MWM) is graph-theoretic approach to inferring RNA secondary structure that shows considerable promise. It takes as input a set of base pairing scores that can be derived from a range of sources, such as free energy considerations, mutual information, or experimental data. These data can be represented as a folding graph where the vertices are alignment positions, and the lines or edges connecting a pair of vertices are given a weight proportional to the amount of evidence for that pairing. A matching is a subgraph of the folding graph in which no vertex is connected to more than one other vertex. The matching with the greatest total edge weight is the taken to be the best estimate of the RNA structure. This matching can include information on both secondary and tertiary structure, such as pseudoknots. MWM can greatly speed up the process of comparative structure analysis of RNA sequences, and has been tested successfully on tRNA, SRP RNA, and 16S rRNA sequences.

Background reading and links

For background on maximum weight matching see JE Tabaska, RB Cary, HN Gabow and GD Stormo (1998), "An RNA folding method capable of identifying pseudoknots and base triples," Bioinformatics 14, 691-699.

A general overview of the comparative analysis of RNA structure is provided by Robin Gutell's Web site.

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