title: Free energy estimation of short DNA duplex hybridizations.
abstract: BACKGROUND
  Estimation of DNA duplex hybridization free energy is widely used for predicting cross-hybridizations in DNA computing and microarray experiments. A number of software programs based on different methods and parametrizations are available for the theoretical estimation of duplex free energies. However, significant differences in free energy values are sometimes observed among estimations obtained with various methods, thus being difficult to decide what value is the accurate one.
  
  
  RESULTS
  We present in this study a quantitative comparison of the similarities and differences among four published DNA/DNA duplex free energy calculation methods and an extended Nearest-Neighbour Model for perfect matches based on triplet interactions. The comparison was performed on a benchmark data set with 695 pairs of short oligos that we collected and manually curated from 29 publications. Sequence lengths range from 4 to 30 nucleotides and span a large GC-content percentage range. For perfect matches, we propose an extension of the Nearest-Neighbour Model that matches or exceeds the performance of the existing ones, both in terms of correlations and root mean squared errors. The proposed model was trained on experimental data with temperature, sodium and sequence concentration characteristics that span a wide range of values, thus conferring the model a higher power of generalization when used for free energy estimations of DNA duplexes under non-standard experimental conditions.
  
  
  CONCLUSIONS
  Based on our preliminary results, we conclude that no statistically significant differences exist among free energy approximations obtained with 4 publicly available and widely used programs, when benchmarked against a collection of 695 pairs of short oligos collected and curated by the authors of this work based on 29 publications. The extended Nearest-Neighbour Model based on triplet interactions presented in this work is capable of performing accurate estimations of free energies for perfect match duplexes under both standard and non-standard experimental conditions and may serve as a baseline for further developments in this area of research.
authors.affiliation: National Research Council of Canada, Institute of Information Technology, 100 des Aboiteaux Street, Suite 1100, Moncton, NB E1A7R1, Canada. dan.tulpan@nrc-cnrc.gc.ca
authors.forename: Dan
authors.initials: D
authors.lastname: Tulpan
authors.forename: Mirela
authors.initials: M
authors.lastname: Andronescu
authors.forename: Serge
authors.initials: S
authors.lastname: Leger
mesh_terms: D000465:Algorithms; D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D009841:Oligonucleotides; D004247:DNA