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Pediatrics Department

Aab Institute

Summary of Research Interests:

Research in the Mathews lab spans the fields of Computational Biology and Bioinformatics. We are interested in predicting RNA structure and we develop computational tools for targeting RNA with pharmaceuticals and for using RNA as a pharmaceutical (Mathews et al., 1999a).

In collaboration with Doug Turner and Michael Zuker, we have developed software that predicts secondary structure, i.e. the canonical base pairs (Mathews et al., 2004; Mathews et al., 1999b). On average, 73% of base pairs are correctly predicted in a set of diverse sequences with known structures. This accuracy can be improved by constraining the structure prediction using data derived from experiments.

We have also developed software that uses a partition function to predict base pairing probabilities (Mathews, 2004). Using this algorithm, secondary structures can be color annotated according to pairing probability to graphically demonstrate both high probability pairs and low probability pairs that are, on average, not as accurate.

Finally, we are developing methods to predict a secondary structure common to multiple sequences (Mathews & Turner, 2002). The accuracy of structure predictions is dramatically improved by using the information contained in multiple sequences. For example, for a set of poorly predicted 5S rRNA sequences, the average accuracy of base pair prediction improves from 47.8% to 86.4% when the structure common to two sequences is determined.

Recent Publications:

1. Mathews, D. H. Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization. RNA 10:1178-1190, 2004

2. Mathews, D. H., Burkard, M. E., Freier, S. M., Wyatt, J. R. & Turner, D. H. Predicting oligonucleotide affinity to nucleic acid targets. RNA 5:1458-1469, 1999a

3. Mathews, D. H., Disney, M. D., Childs, J. L., Schroeder, S. J., Zuker, M. & Turner, D. H. Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc Natl Acad Sci USA 101:7287-7292, 2004

4. Mathews, D. H., Sabina, J., Zuker, M. & Turner, D. H. Expanded sequence dependence of thermodynamic parameters provides improved prediction of RNA secondary structure. J Mol Biol 288:911-940, 1999b

5. Mathews, D. H. & Turner, D. H. Dynalign: An algorithm for finding the secondary structure common to two RNA sequences. J Mol Biol 317:191-203, 2002

    

LAST MODIFIED: Jan 2005
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