Modeling of DNA microarray data by using physical properties of hybridization

A method of analyzing DNA microarray data based on the physical modeling of hybridization is presented. We demonstrate, in experimental data, a correlation between observed hybridization intensity and calculated free energy of hybridization. Then, combining hybridization rate equations, calculated free energies of hybridization, and microarray data for known target concentrations, we construct an algorithm to compute transcript concentration levels from microarray data. We also develop a method for eliminating outlying data points identified by our algorithm. We test the efficacy of these methods by comparing our results with an existing statistical algorithm, as well as by performing a cross-validation test on our model.

[1]  T. Kepler,et al.  Normalization and analysis of DNA microarray data by self-consistency and local regression , 2002, Genome Biology.

[2]  C. Cantor,et al.  Biophysical chemistry. Part III, The behavior of biologicalmacromolecules , 1980 .

[3]  J. SantaLucia,et al.  Nearest-neighbor thermodynamics and NMR of DNA sequences with internal A.A, C.C, G.G, and T.T mismatches. , 1999, Biochemistry.

[4]  D. Slonim,et al.  Evaluation of normalization procedures for oligonucleotide array data based on spiked cRNA controls , 2001, Genome Biology.

[5]  R. Stoughton,et al.  Use of hybridization kinetics for differentiating specific from non-specific binding to oligonucleotide microarrays. , 2002, Nucleic acids research.

[6]  Y. Tu,et al.  Quantitative noise analysis for gene expression microarray experiments , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Japan K K Affymetrix,et al.  New Statistical Algorithms for Monitoring Gene Expression on GeneChip Probe Arrays , 2001 .

[8]  Felix Naef,et al.  Absolute mRNA concentrations from sequence-specific calibration of oligonucleotide arrays. , 2003, Nucleic acids research.

[9]  C. Li,et al.  Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. SantaLucia,et al.  A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Felix Naef,et al.  Empirical characterization of the expression ratio noise structure in high-density oligonucleotide arrays , 2002, Genome Biology.

[12]  Neocles B. Leontis,et al.  Molecular modeling of nucleic acids , 1997 .

[13]  S. P. Fodor,et al.  High density synthetic oligonucleotide arrays , 1999, Nature Genetics.

[14]  M. Dugas,et al.  Profound effect of normalization on detection of differentially expressed genes in oligonucleotide microarray data analysis , 2002, Genome Biology.

[15]  D. Mount.  Bioinformatics: Sequence and Genome Analysis , 2001 .