Graduate Program Information
My Contact Information

Assistant Professor of Biochemistry and Biophysics
Ph.D. University of Rochester 2002
M.D. University of Rochester 2003

Our understanding of the role of RNA in cellular processes has expanded enormously over the last two decades. Originally, RNA was understood to participate in protein expression as a carrier of genetic information (mRNA) and as an adapter molecule (tRNA) for reading the code. Then RNA was discovered to catalyze reactions, including self-splicing, phosphodiester bond cleavage, and peptide bond formation. RNA is now known to play functions in diverse cellular processes, such as development, immunity, RNA editing and modification, and post-transcriptional gene regulation. RNA is also an important player in many diseases, including Prader-Willi, b-thalassemia, and myotonic dystrophy. RNA sequences can be evolved in vitro to catalyze many reactions that are not part of the natural repertoire. Antisense and RNAi can be used to modulate gene expression.

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 (University of Rochester) and Michael Zuker (RPI), 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.

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Recent Publications

Lu ZJ, Mathews DH (2008) Fundamental differences in the equilibrium considerations for siRNA and antisense oligodeoxynucleotide design. Nucleic Acids Res,

Lu ZJ, Mathews DH (2008) OligoWalk: an online siRNA design tool utilizing hybridization thermodynamics. Nucleic Acids Res, 36:W104-8

Lu ZJ, Mathews DH (2008) Efficient siRNA selection using hybridization thermodynamics. Nucleic Acids Res, 36:640-7

Hart JM, Kennedy SD, Mathews DH, Turner DH (2008) NMR-assisted prediction of RNA secondary structure: identification of a probable pseudoknot in the coding region of an R2 retrotransposon. J Am Chem Soc, 130:10233-9

Wilkinson KA, Gorelick RJ, Vasa SM, Guex N, Rein A, Mathews DH, Giddings MC, Weeks KM (2008) High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states. PLoS Biol, 6:e96

Harmanci AO, Sharma G, Mathews DH (2008) PARTS: probabilistic alignment for RNA joinT secondary structure prediction. Nucleic Acids Res, 36:2406-17

Andronescu M, Condon A, Hoos HH, Mathews DH, Murphy KP (2007) Efficient parameter estimation for RNA secondary structure prediction. Bioinformatics, 23:i19-28

Tyagi R, Mathews DH (2007) Predicting helical coaxial stacking in RNA multibranch loops. Rna, 13:939-51

Harmanci AO, Sharma G, Mathews DH (2007) Efficient pairwise RNA structure prediction using probabilistic alignment constraints in Dynalign. BMC Bioinformatics, 8:130

Uzilov AV, Keegan JM, Mathews DH (2006) Detection of non-coding RNAs on the basis of predicted secondary structure formation free energy change. BMC Bioinformatics, 7:173

Mathews DH (2006) Revolutions in RNA secondary structure prediction. J Mol Biol, 359:526-32

Mathews DH, Turner DH (2006) Prediction of RNA secondary structure by free energy minimization. Curr Opin Struct Biol, 16:270-8

Duan S, Mathews DH, Turner DH (2006) Interpreting oligonucleotide microarray data to determine RNA secondary structure: application to the 3' end of Bombyx mori R2 RNA. Biochemistry, 45:9819-32

Mathews DH, Case DA (2006) Nudged elastic band calculation of minimal energy paths for the conformational change of a GG non-canonical pair. J Mol Biol, 357:1683-93

Leontis NB, Altman RB, Berman HM, Brenner SE, Brown JW, Engelke DR, Harvey SC, Holbrook SR, Jossinet F, Lewis SE, Major F, Mathews DH, Richardson JS, Williamson JR, Westhof E (2006) The RNA Ontology Consortium: an open invitation to the RNA community. RNA, 12:533-41

Kierzek E, Mathews DH, Ciesielska A, Turner DH, Kierzek R (2006) Nearest neighbor parameters for Watson-Crick complementary heteroduplexes formed between 2'-O-methyl RNA and RNA oligonucleotides. Nucleic Acids Res, 34:3609-14

Lu ZJ, Turner DH, Mathews DH (2006) A set of nearest neighbor parameters for predicting the enthalpy change of RNA secondary structure formation. Nucleic Acids Res, 34:4912-24

Mathews DH (2005) Predicting a set of minimal free energy RNA secondary structures common to two sequences. Bioinformatics, 21:2246-53

Kierzek E, Ciesielska A, Pasternak K, Mathews DH, Turner DH, Kierzek R (2005) The influence of locked nucleic acid residues on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes. Nucleic Acids Res, 33:5082-93

Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH (2004) Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc Natl Acad Sci U S A, 101:7287-92

Ruschak AM, Mathews DH, Bibillo A, Spinelli SL, Childs JL, Eickbush TH, Turner DH (2004) Secondary structure models of the 3' untranslated regions of diverse R2 RNAs. RNA, 10:978-87

Mathews DH (2004) Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization. RNA, 10:1178-90

Mathews DH, Turner DH (2002) Dynalign: an algorithm for finding the secondary structure common to two RNA sequences. J Mol Biol, 317:191-203

Mathews DH, Burkard ME, Freier SM, Wyatt JR, Turner DH (1999) Predicting oligonucleotide affinity to nucleic acid targets. RNA, 5:1458-69

Mathews DH, Sabina J, Zuker M, Turner DH (1999) Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol, 288:911-40

Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:

Ph.D. in Biochemistry
Ph.D. in Biophysics

Ph.D. candidates in my laboratory may also be affiliated with these programs:

Contact Information

E-Mail: David_Mathews@urmc.rochester.edu

David Mathews
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center 3-6830
Telephone: (585) 275-1734; Fax: (585) 275-6007