Using Sequence-Specific Chemical and Structural Properties of DNA to Predict Transcription Factor Binding Sites

Bauer, Amy L.; Hlavacek, William S.; Unkefer, Pat J.; Mu, Fangping

doi:10.1371/journal.pcbi.1001007

Title: Using Sequence-Specific Chemical and Structural Properties of DNA to Predict Transcription Factor Binding Sites

Journal Article · Thu Nov 18 00:00:00 EST 2010 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.1001007· OSTI ID:1627207

Bauer, Amy L. ^[1]; Hlavacek, William S. ^[1]; Unkefer, Pat J. ^[2]; Mu, Fangping ^[1]

Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division. Theoretical Biology and Biophysics Group
Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Bioscience Division. National Stable Isotope Resource

An important step in understanding gene regulation is to identify the DNA binding sites recognized by each transcription factor (TF). Conventional approaches to prediction of TF binding sites involve the definition of consensus sequences or position-specific weight matrices and rely on statistical analysis of DNA sequences of known binding sites. Here, we present a method called SiteSleuth in which DNA structure prediction, computational chemistry, and machine learning are applied to develop models for TF binding sites. In this approach, binary classifiers are trained to discriminate between true and false binding sites based on the sequence-specific chemical and structural features of DNA. These features are determined via molecular dynamics calculations in which we consider each base in different local neighborhoods. For each of 54 TFs in Escherichia coli, for which at least five DNA binding sites are documented in RegulonDB, the TF binding sites and portions of the non-coding genome sequence are mapped to feature vectors and used in training. According to cross-validation analysis and a comparison of computational predictions against ChIP-chip data available for the TF Fis, SiteSleuth outperforms three conventional approaches: Match, MATRIX SEARCH, and the method of Berg and von Hippel. SiteSleuth also outperforms QPMEME, a method similar to SiteSleuth in that it involves a learning algorithm. The main advantage of SiteSleuth is a lower false positive rate.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1627207

Journal Information:: PLoS Computational Biology (Online), Vol. 6, Issue 11; ISSN 1553-7358

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (43)

Selection of DNA binding sites by regulatory proteins Berg, Otto G.; von Hippel, Peter H. Journal of Molecular Biology, Vol. 193, Issue 4 https://doi.org/10.1016/0022-2836(87)90354-8	journal	February 1987
MatInspector and beyond: promoter analysis based on transcription factor binding sites Cartharius, K.; Frech, K.; Grote, K. Bioinformatics, Vol. 21, Issue 13 https://doi.org/10.1093/bioinformatics/bti473	journal	April 2005
A Biophysical Approach to Transcription Factor Binding Site Discovery Djordjevic, M. Genome Research, Vol. 13, Issue 11 https://doi.org/10.1101/gr.1271603	journal	November 2003
MATCHTM: a tool for searching transcription factor binding sites in DNA sequences Kel, A. E. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg585	journal	July 2003
Comparative analysis of methods for representing and searching for transcription factor binding sites Osada, R.; Zaslavsky, E.; Singh, M. Bioinformatics, Vol. 20, Issue 18 https://doi.org/10.1093/bioinformatics/bth438	journal	August 2004
Matlnd and Matlnspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data Quandt, Kerstin; Frech, Kornelie; Karas, Holger Nucleic Acids Research, Vol. 23, Issue 23 https://doi.org/10.1093/nar/23.23.4878	journal	January 1995
DNA binding sites: representation and discovery Stormo, G. D. Bioinformatics, Vol. 16, Issue 1 https://doi.org/10.1093/bioinformatics/16.1.16	journal	January 2000
Ab Initio Prediction of Transcription Factor Targets Using Structural Knowledge Kaplan, Tommy; Friedman, Nir; Margalit, Hanah PLoS Computational Biology, Vol. 1, Issue 1 https://doi.org/10.1371/journal.pcbi.0010001	journal	June 2005
Toward an atomistic model for predicting transcription-factor binding sites Endres, Robert G.; Schulthess, Thomas C.; Wingreen, Ned S. Proteins: Structure, Function, and Bioinformatics, Vol. 57, Issue 2 https://doi.org/10.1002/prot.20199	journal	June 2004
Protein-DNA binding specificity predictions with structural models Morozov, A. V. Nucleic Acids Research, Vol. 33, Issue 18 https://doi.org/10.1093/nar/gki875	journal	October 2005
Connecting protein structure with predictions of regulatory sites Morozov, A. V.; Siggia, E. D. Proceedings of the National Academy of Sciences, Vol. 104, Issue 17, p. 7068-7073 https://doi.org/10.1073/pnas.0701356104	journal	April 2007
Universal protein-binding microarrays for the comprehensive characterization of the DNA-binding specificities of transcription factors Berger, Michael F.; Bulyk, Martha L. Nature Protocols, Vol. 4, Issue 3 https://doi.org/10.1038/nprot.2008.195	journal	March 2009
Genome-wide analysis of Fis binding in Escherichia coli indicates a causative role for A-/AT-tracts Cho, B. -K.; Knight, E. M.; Barrett, C. L. Genome Research, Vol. 18, Issue 6 https://doi.org/10.1101/gr.070276.107	journal	May 2008
A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors Maerkl, S. J.; Quake, S. R. Science, Vol. 315, Issue 5809 https://doi.org/10.1126/science.1131007	journal	January 2007
Protein-DNA Recognition Patterns and Predictions Sarai, Akinori; Kono, Hidetoshi Annual Review of Biophysics and Biomolecular Structure, Vol. 34, Issue 1 https://doi.org/10.1146/annurev.biophys.34.040204.144537	journal	June 2005
Indirect readout: detection of optimized subsequences and calculation of relative binding affinities using different DNA elastic potentials Becker, Nils B.; Wolff, Lars; Everaers, Ralf Nucleic Acids Research, Vol. 34, Issue 19 https://doi.org/10.1093/nar/gkl683	journal	October 2006
Predicting indirect readout effects in protein-DNA interactions Zhang, Y.; Xi, Z.; Hegde, R. S. Proceedings of the National Academy of Sciences, Vol. 101, Issue 22 https://doi.org/10.1073/pnas.0402319101	journal	May 2004
ReadOut: structure-based calculation of direct and indirect readout energies and specificities for protein-DNA recognition Ahmad, S.; Kono, H.; Arauzo-Bravo, M. J. Nucleic Acids Research, Vol. 34, Issue Web Server https://doi.org/10.1093/nar/gkl104	journal	July 2006
Intermolecular and Intramolecular Readout Mechanisms in Protein–DNA Recognition Michael Gromiha, M.; Siebers, Jörg G.; Selvaraj, Samuel Journal of Molecular Biology, Vol. 337, Issue 2 https://doi.org/10.1016/j.jmb.2004.01.033	journal	March 2004
RegulonDB (version 6.0): gene regulation model of Escherichia coli K-12 beyond transcription, active (experimental) annotated promoters and Textpresso navigation Gama-Castro, S.; Jimenez-Jacinto, V.; Peralta-Gil, M. Nucleic Acids Research, Vol. 36, Issue Database https://doi.org/10.1093/nar/gkm994	journal	December 2007
Chromatin Immunoprecipitation for Determining the Association of Proteins with Specific Genomic Sequences In Vivo Aparicio, Oscar; Geisberg, Joseph V.; Struhl, Kevin Current Protocols in Cell Biology, Vol. 23, Issue 1 https://doi.org/10.1002/0471143030.cb1707s23	journal	June 2004
Simulation and modeling of nucleic acid structure, dynamics and interactions Cheatham, Thomas E. Current Opinion in Structural Biology, Vol. 14, Issue 3 https://doi.org/10.1016/j.sbi.2004.05.001	journal	June 2004
Recent advances in the study of nucleic acid flexibility by molecular dynamics Orozco, Modesto; Noy, Agnes; Pérez, Alberto Current Opinion in Structural Biology, Vol. 18, Issue 2 https://doi.org/10.1016/j.sbi.2008.01.005	journal	April 2008
Molecular Dynamics Simulations of the 136 Unique Tetranucleotide Sequences of DNA Oligonucleotides. I. Research Design and Results on d(CpG) Steps Beveridge, David L.; Barreiro, Gabriela; Suzie Byun, K. Biophysical Journal, Vol. 87, Issue 6 https://doi.org/10.1529/biophysj.104.045252	journal	December 2004
Molecular Dynamics Simulations of the 136 Unique Tetranucleotide Sequences of DNA Oligonucleotides. II: Sequence Context Effects on the Dynamical Structures of the 10 Unique Dinucleotide Steps Dixit, Surjit B.; Beveridge, David L.; Case, David A. Biophysical Journal, Vol. 89, Issue 6 https://doi.org/10.1529/biophysj.105.067397	journal	December 2005
A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA Lavery, Richard; Zakrzewska, Krystyna; Beveridge, David Nucleic Acids Research, Vol. 38, Issue 1 https://doi.org/10.1093/nar/gkp834	journal	November 2009
The nucleic acid database. A comprehensive relational database of three-dimensional structures of nucleic acids Berman, H. M.; Olson, W. K.; Beveridge, D. L. Biophysical Journal, Vol. 63, Issue 3 https://doi.org/10.1016/S0006-3495(92)81649-1	journal	September 1992
3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures Lu, X. -J. Nucleic Acids Research, Vol. 31, Issue 17 https://doi.org/10.1093/nar/gkg680	journal	September 2003
Scalable molecular dynamics with NAMD Phillips, James C.; Braun, Rosemary; Wang, Wei Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802 https://doi.org/10.1002/jcc.20289	journal	January 2005
All-atom empirical force field for nucleic acids: I. Parameter optimization based on small molecule and condensed phase macromolecular target data Foloppe, Nicolas; MacKerell, Jr., Alexander D. Journal of Computational Chemistry, Vol. 21, Issue 2 https://doi.org/10.1002/(SICI)1096-987X(20000130)21:2<86::AID-JCC2>3.0.CO;2-G	journal	January 2000
A standard reference frame for the description of nucleic acid base-pair geometry 1 1Edited by P. E. Wright 2 2This is a document of the Nomenclature Committee of IUBMB (NC-IUBMB)/IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN), whose members are R. Cammack (chairman), A. Bairoch, H.M. Berman, S. Boyce, C.R. Cantor, K. Elliott, D. Horton, M. Kanehisa, A. Kotyk, G.P. Moss, N. Sharon and K.F. Tipton. Olson, Wilma K.; Bansal, Manju; Burley, Stephen K. Journal of Molecular Biology, Vol. 313, Issue 1 https://doi.org/10.1006/jmbi.2001.4987	journal	October 2001
A computational procedure for determining energetically favorable binding sites on biologically important macromolecules Goodford, P. J. Journal of Medicinal Chemistry, Vol. 28, Issue 7 https://doi.org/10.1021/jm00145a002	journal	July 1985
From genomics to chemical genomics: new developments in KEGG Kanehisa, M. Nucleic Acids Research, Vol. 34, Issue 90001 https://doi.org/10.1093/nar/gkj102	journal	January 2006
A comprehensive library of DNA-binding site matrices for 55 proteins applied to the complete Escherichia coli K-12 genome 1 1Edited by R. Ebright Robison, Keith; McGuire, Abigail Manson; Church, George M. Journal of Molecular Biology, Vol. 284, Issue 2 https://doi.org/10.1006/jmbi.1998.2160	journal	November 1998
An introduction to ROC analysis Fawcett, Tom Pattern Recognition Letters, Vol. 27, Issue 8 https://doi.org/10.1016/j.patrec.2005.10.010	journal	June 2006
Glycine binds the transcriptional accessory protein GcvR to disrupt a GcvA/GcvR interaction and allow GcvA-mediated activation of the Escherichia coli gcvTHP operon Heil, Gary; Stauffer, Lorraine T.; Stauffer, George V. Microbiology, Vol. 148, Issue 7 https://doi.org/10.1099/00221287-148-7-2203	journal	July 2002
Crystal structure of the Escherichia coli Rob transcription factor in complex with DNA Kwon, Hyock Joo; Bennik, Marjon H. J.; Demple, Bruce Nature Structural Biology, Vol. 7, Issue 5, p. 424-430 https://doi.org/10.1038/75213	journal	May 2000
Additivity in protein-DNA interactions: how good an approximation is it? Benos, P. V. Nucleic Acids Research, Vol. 30, Issue 20 https://doi.org/10.1093/nar/gkf578	journal	October 2002
The shape of the DNA minor groove directs binding by the DNA-bending protein Fis Stella, S.; Cascio, D.; Johnson, R. C. Genes & Development, Vol. 24, Issue 8 https://doi.org/10.1101/gad.1900610	journal	April 2010
Probabilistic Code for DNA Recognition by Proteins of the EGR Family Benos, Panayiotis V.; Lapedes, Alan S.; Stormo, Gary D. Journal of Molecular Biology, Vol. 323, Issue 4 https://doi.org/10.1016/s0022-2836(02)00917-8	journal	November 2002
Design Principles for Regulator Gene Expression in a Repressible Gene Circuit Wall, Michael E.; Hlavacek, William S.; Savageau, Michael A. Journal of Molecular Biology, Vol. 332, Issue 4 https://doi.org/10.1016/s0022-2836(03)00948-3	journal	September 2003
Simulation and modeling of nucleic acid structure, dynamics and interactions Cheatham, T. Current Opinion in Structural Biology https://doi.org/10.1016/s0959-440x(04)00075-2	journal	May 2004
MATRIX SEARCH 1.0: a computer program that scans DNA sequences for transcriptional elements using a database of weight matrices Chen, Qing K.; Hertz, Gerald Z.; Stormo, Gary D. Bioinformatics, Vol. 11, Issue 5 https://doi.org/10.1093/bioinformatics/11.5.563	journal	January 1995

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