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David Mathews

TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentBiochemistry and Biophysics
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester NY 14642
Other Positions
TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentBiostatistics and Computational Biology

 
 Overview
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.

 
 Selected Publications
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  1. Stern HA, Mathews DH. Accelerating calculations of RNA secondary structure partition functions using GPUs. Algorithms Mol Biol. 2013; 8(1):29.
    View in: PubMed
  2. Bellaousov S, Reuter JS, Seetin MG, Mathews DH. RNAstructure: web servers for RNA secondary structure prediction and analysis. Nucleic Acids Res. 2013 Jul 1; 41(Web Server issue):W471-4.
    View in: PubMed
  3. Hajdin CE, Bellaousov S, Huggins W, Leonard CW, Mathews DH, Weeks KM. Accurate SHAPE-directed RNA secondary structure modeling, including pseudoknots. Proc Natl Acad Sci U S A. 2013 Apr 2; 110(14):5498-503.
    View in: PubMed
  4. Shen M, Bellaousov S, Hiller M, de La Grange P, Creamer TP, Malina O, Sperling R, Mathews DH, Stoilov P, Stamm S. Pyrvinium pamoate changes alternative splicing of the serotonin receptor 2C by influencing its RNA structure. Nucleic Acids Res. 2013 Apr 1; 41(6):3819-32.
    View in: PubMed
  5. Leonard CW, Hajdin CE, Karabiber F, Mathews DH, Favorov OV, Dokholyan NV, Weeks KM. Principles for Understanding the Accuracy of SHAPE-Directed RNA Structure Modeling. Biochemistry. 2013 Jan 29; 52(4):588-95.
    View in: PubMed
  6. Schmidt K, Xu Z, Mathews DH, Butler JS. Air proteins control differential TRAMP substrate specificity for nuclear RNA surveillance. RNA. 2012 Oct; 18(10):1934-45.
    View in: PubMed
  7. Seetin MG, Mathews DH. TurboKnot: rapid prediction of conserved RNA secondary structures including pseudoknots. Bioinformatics. 2012 Mar 15; 28(6):792-8.
    View in: PubMed
  8. Seetin MG, Mathews DH. RNA structure prediction: an overview of methods. Methods Mol Biol. 2012; 905:99-122.
    View in: PubMed
  9. Xu Z, Almudevar A, Mathews DH. Statistical evaluation of improvement in RNA secondary structure prediction. Nucleic Acids Res. 2012 Feb; 40(4):e26.
    View in: PubMed
  10. Rocca-Serra P, Bellaousov S, Birmingham A, Chen C, Cordero P, Das R, Davis-Neulander L, Duncan CD, Halvorsen M, Knight R, Leontis NB, Mathews DH, Ritz J, Stombaugh J, Weeks KM, Zirbel CL, Laederach A. Sharing and archiving nucleic acid structure mapping data. RNA. 2011 Jul; 17(7):1204-12.
    View in: PubMed
  11. Noble E, Mathews DH, Chen JL, Turner DH, Takimoto T, Kim B. Biophysical analysis of influenza A virus RNA promoter at physiological temperatures. J Biol Chem. 2011 Jul 1; 286(26):22965-70.
    View in: PubMed
  12. Vockenhuber MP, Sharma CM, Statt MG, Schmidt D, Xu Z, Dietrich S, Liesegang H, Mathews DH, Suess B. Deep sequencing-based identification of small non-coding RNAs in Streptomyces coelicolor. RNA Biol. 2011 May-Jun; 8(3):468-77.
    View in: PubMed
  13. Harmanci AO, Sharma G, Mathews DH. TurboFold: iterative probabilistic estimation of secondary structures for multiple RNA sequences. BMC Bioinformatics. 2011; 12:108.
    View in: PubMed
  14. Liu B, Diamond JM, Mathews DH, Turner DH. Fluorescence competition and optical melting measurements of RNA three-way multibranch loops provide a revised model for thermodynamic parameters. Biochemistry. 2011 Feb 8; 50(5):640-53.
    View in: PubMed
  15. Xu Z, Mathews DH. Multilign: an algorithm to predict secondary structures conserved in multiple RNA sequences. Bioinformatics. 2011 Mar 1; 27(5):626-32.
    View in: PubMed
  16. Nasrallah CA, Mathews DH, Huelsenbeck JP. Quantifying the impact of dependent evolution among sites in phylogenetic inference. Syst Biol. 2011 Jan; 60(1):60-73.
    View in: PubMed
  17. Underwood JG, Uzilov AV, Katzman S, Onodera CS, Mainzer JE, Mathews DH, Lowe TM, Salama SR, Haussler D. FragSeq: transcriptome-wide RNA structure probing using high-throughput sequencing. Nat Methods. 2010 Dec; 7(12):995-1001.
    View in: PubMed
  18. Andronescu M, Condon A, Hoos HH, Mathews DH, Murphy KP. Computational approaches for RNA energy parameter estimation. RNA. 2010 Dec; 16(12):2304-18.
    View in: PubMed
  19. Bellaousov S, Mathews DH. ProbKnot: fast prediction of RNA secondary structure including pseudoknots. RNA. 2010 Oct; 16(10):1870-80.
    View in: PubMed
  20. Mathews DH, Moss WN, Turner DH. Folding and finding RNA secondary structure. Cold Spring Harb Perspect Biol. 2010 Dec; 2(12):a003665.
    View in: PubMed
  21. Reuter JS, Mathews DH. RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics. 2010; 11:129.
    View in: PubMed
  22. Liu B, Mathews DH, Turner DH. RNA pseudoknots: folding and finding. F1000 Biol Rep. 2010; 2:8.
    View in: PubMed
  23. Mathews DH. Using OligoWalk to identify efficient siRNA sequences. Methods Mol Biol. 2010; 629:109-21.
    View in: PubMed
  24. Piekna-Przybylska D, DiChiacchio L, Mathews DH, Bambara RA. A sequence similar to tRNA 3 Lys gene is embedded in HIV-1 U3-R and promotes minus-strand transfer. Nat Struct Mol Biol. 2010 Jan; 17(1):83-9.
    View in: PubMed
  25. Turner DH, Mathews DH. NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure. Nucleic Acids Res. 2010 Jan; 38(Database issue):D280-2.
    View in: PubMed
  26. Rigby ST, Van Nostrand KP, Rose AE, Gorelick RJ, Mathews DH, Bambara RA. Factors that determine the efficiency of HIV-1 strand transfer initiated at a specific site. J Mol Biol. 2009 Dec 11; 394(4):694-707.
    View in: PubMed
  27. Lu ZJ, Gloor JW, Mathews DH. Improved RNA secondary structure prediction by maximizing expected pair accuracy. RNA. 2009 Oct; 15(10):1805-13.
    View in: PubMed
  28. Harmanci AO, Sharma G, Mathews DH. Stochastic sampling of the RNA structural alignment space. Nucleic Acids Res. 2009 Jul; 37(12):4063-75.
    View in: PubMed
  29. Deigan KE, Li TW, Mathews DH, Weeks KM. Accurate SHAPE-directed RNA structure determination. Proc Natl Acad Sci U S A. 2009 Jan 6; 106(1):97-102.
    View in: PubMed
  30. Hart JM, Kennedy SD, Mathews DH, Turner DH. NMR-assisted prediction of RNA secondary structure: identification of a probable pseudoknot in the coding region of an R2 retrotransposon. J Am Chem Soc. 2008 Aug 6; 130(31):10233-9.
    View in: PubMed
  31. Lu ZJ, Mathews DH. OligoWalk: an online siRNA design tool utilizing hybridization thermodynamics. Nucleic Acids Res. 2008 Jul 1; 36(Web Server issue):W104-8.
    View in: PubMed
  32. Lu ZJ, Mathews DH. Fundamental differences in the equilibrium considerations for siRNA and antisense oligodeoxynucleotide design. Nucleic Acids Res. 2008 Jun; 36(11):3738-45.
    View in: PubMed
  33. Wilkinson KA, Gorelick RJ, Vasa SM, Guex N, Rein A, Mathews DH, Giddings MC, Weeks KM. High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states. PLoS Biol. 2008 Apr 29; 6(4):e96.
    View in: PubMed
  34. Harmanci AO, Sharma G, Mathews DH. PARTS: probabilistic alignment for RNA joinT secondary structure prediction. Nucleic Acids Res. 2008 Apr; 36(7):2406-17.
    View in: PubMed
  35. Lu ZJ, Mathews DH. Efficient siRNA selection using hybridization thermodynamics. Nucleic Acids Res. 2008 Feb; 36(2):640-7.
    View in: PubMed
  36. Shankar N, Xia T, Kennedy SD, Krugh TR, Mathews DH, Turner DH. NMR reveals the absence of hydrogen bonding in adjacent UU and AG mismatches in an isolated internal loop from ribosomal RNA. Biochemistry. 2007 Nov 6; 46(44):12665-78.
    View in: PubMed
  37. Andronescu M, Condon A, Hoos HH, Mathews DH, Murphy KP. Efficient parameter estimation for RNA secondary structure prediction. Bioinformatics. 2007 Jul 1; 23(13):i19-28.
    View in: PubMed
  38. Tyagi R, Mathews DH. Predicting helical coaxial stacking in RNA multibranch loops. RNA. 2007 Jul; 13(7):939-51.
    View in: PubMed
  39. Harmanci AO, Sharma G, Mathews DH. Efficient pairwise RNA structure prediction using probabilistic alignment constraints in Dynalign. BMC Bioinformatics. 2007; 8:130.
    View in: PubMed
  40. Mathews DH, Turner DH, Zuker M. RNA secondary structure prediction. Curr Protoc Nucleic Acid Chem. 2007 Mar; Chapter 11:Unit 11.2.
    View in: PubMed
  41. Lu ZJ, Turner DH, Mathews DH. A set of nearest neighbor parameters for predicting the enthalpy change of RNA secondary structure formation. Nucleic Acids Res. 2006; 34(17):4912-24.
    View in: PubMed
  42. Duan S, Mathews DH, Turner DH. Interpreting oligonucleotide microarray data to determine RNA secondary structure: application to the 3' end of Bombyx mori R2 RNA. Biochemistry. 2006 Aug 15; 45(32):9819-32.
    View in: PubMed
  43. Kierzek E, Mathews DH, Ciesielska A, Turner DH, Kierzek R. Nearest neighbor parameters for Watson-Crick complementary heteroduplexes formed between 2'-O-methyl RNA and RNA oligonucleotides. Nucleic Acids Res. 2006; 34(13):3609-14.
    View in: PubMed
  44. Mathews DH, Turner DH. Prediction of RNA secondary structure by free energy minimization. Curr Opin Struct Biol. 2006 Jun; 16(3):270-8.
    View in: PubMed
  45. Uzilov AV, Keegan JM, Mathews DH. Detection of non-coding RNAs on the basis of predicted secondary structure formation free energy change. BMC Bioinformatics. 2006; 7:173.
    View in: PubMed
  46. Mathews DH. RNA secondary structure analysis using RNAstructure. Curr Protoc Bioinformatics. 2006 Mar; Chapter 12:Unit 12.6.
    View in: PubMed
  47. 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. The RNA Ontology Consortium: an open invitation to the RNA community. RNA. 2006 Apr; 12(4):533-41.
    View in: PubMed
  48. Mathews DH. Revolutions in RNA secondary structure prediction. J Mol Biol. 2006 Jun 9; 359(3):526-32.
    View in: PubMed
  49. Mathews DH, Case DA. Nudged elastic band calculation of minimal energy paths for the conformational change of a GG non-canonical pair. J Mol Biol. 2006 Apr 14; 357(5):1683-93.
    View in: PubMed
  50. Kierzek E, Ciesielska A, Pasternak K, Mathews DH, Turner DH, Kierzek R. The influence of locked nucleic acid residues on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes. Nucleic Acids Res. 2005; 33(16):5082-93.
    View in: PubMed
  51. Mathews DH. Predicting a set of minimal free energy RNA secondary structures common to two sequences. Bioinformatics. 2005 May 15; 21(10):2246-53.
    View in: PubMed
  52. Mathews D. Predicting the secondary structure common to two RNA sequences with Dynalign. Curr Protoc Bioinformatics. 2004 Dec; Chapter 12:Unit 12.4.
    View in: PubMed
  53. Mathews DH. Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization. RNA. 2004 Aug; 10(8):1178-90.
    View in: PubMed
  54. Ruschak AM, Mathews DH, Bibillo A, Spinelli SL, Childs JL, Eickbush TH, Turner DH. Secondary structure models of the 3' untranslated regions of diverse R2 RNAs. RNA. 2004 Jun; 10(6):978-87.
    View in: PubMed
  55. Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH. Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc Natl Acad Sci U S A. 2004 May 11; 101(19):7287-92.
    View in: PubMed
  56. Matveeva OV, Mathews DH, Tsodikov AD, Shabalina SA, Gesteland RF, Atkins JF, Freier SM. Thermodynamic criteria for high hit rate antisense oligonucleotide design. Nucleic Acids Res. 2003 Sep 1; 31(17):4989-94.
    View in: PubMed
  57. Mathews DH, Turner DH. Use of chemical modification to elucidate RNA folding pathways. Curr Protoc Nucleic Acid Chem. 2002 Aug; Chapter 11:Unit 11.9.
    View in: PubMed
  58. Mathews DH, Turner DH. Dynalign: an algorithm for finding the secondary structure common to two RNA sequences. J Mol Biol. 2002 Mar 22; 317(2):191-203.
    View in: PubMed
  59. Mathews DH, Turner DH. Experimentally derived nearest-neighbor parameters for the stability of RNA three- and four-way multibranch loops. Biochemistry. 2002 Jan 22; 41(3):869-80.
    View in: PubMed
  60. Diamond JM, Turner DH, Mathews DH. Thermodynamics of three-way multibranch loops in RNA. Biochemistry. 2001 Jun 12; 40(23):6971-81.
    View in: PubMed
  61. Mathews DH, Burkard ME, Freier SM, Wyatt JR, Turner DH. Predicting oligonucleotide affinity to nucleic acid targets. RNA. 1999 Nov; 5(11):1458-69.
    View in: PubMed
  62. Mathews DH, Sabina J, Zuker M, Turner DH. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol. 1999 May 21; 288(5):911-40.
    View in: PubMed
  63. Mathews DH, Banerjee AR, Luan DD, Eickbush TH, Turner DH. Secondary structure model of the RNA recognized by the reverse transcriptase from the R2 retrotransposable element. RNA. 1997 Jan; 3(1):1-16.
    View in: PubMed
  64. Li Y, Bevilacqua PC, Mathews D, Turner DH. Thermodynamic and activation parameters for binding of a pyrene-labeled substrate by the Tetrahymena ribozyme: docking is not diffusion-controlled and is driven by a favorable entropy change. Biochemistry. 1995 Nov 7; 34(44):14394-9.
    View in: PubMed
  65. Walter AE, Turner DH, Kim J, Lyttle MH, Müller P, Mathews DH, Zuker M. Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding. Proc Natl Acad Sci U S A. 1994 Sep 27; 91(20):9218-22.
    View in: PubMed

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