SURVEY AND SUMMARY Physico-chemical foundations underpinning microarray and next-generation sequencing experiments Andrew Harrison 1 , Hans Binder 2 , Arnaud Buhot 3 , Conrad J. Burden 4 , Enrico Carlon 5 , Cynthia Gibas 6 , Lara J. Gamble 7 , Avraham Halperin 8 , Jef Hooyberghs 9 , David P. Kreil 10,11 , Rastislav Levicky 12 , Peter A. Noble 13,14 , Albrecht Ott 15 , B. Montgomery Pettitt 16 , Diethard Tautz 17 and Alexander E. Pozhitkov 14,17, * 1 University of Essex-Mathematical Sciences, Colchester CO4 3SQ, Essex, United Kingdom, 2 University Leipzig, Interdisciplinary Center for Bioinformatics, Leipzig, D-4107, Germany, 3 SPrAM (UMR 5819: CEA, CNRS, UJF), INAC, CEA Grenoble, 17 rue des Martyrs, 38054 Grenoble cedex 9, France, 4 Centre for Bioinformation Science, Mathematical Sciences Institute Building 27 Australian National University, Canberra, Australian Capital Territory 0200, Australia, 5 K.U. Leuven - Physics, Celestijnenlaan 200D B-3000 Leuven, Belgium, 6 University of North Carolina at Charlotte-Bioinformatics Research Center, Charlotte, NC 28223-0001, USA, 7 University of Washington-Bioengineering, Seattle, WA 98195, USA, 8 University of Grenoble - National Center for Scientific Research, 38041, Grenoble, France, 9 Flemish Institute for Technological Research (VITO) - Toxicology, Boeretang 200, Mol 2400, Belgium, 10 Universita ¨t fu ¨ r Bodenkultur Wien - Biotechnologie, Wien, Austria, 11 Life Sciences, University of Warwick, Coventry CV4 7AL, UK 12 Polytechnic Institute of New York University - Chemical and Biological Engineering, 6 MetroTech Center, Brooklyn, NY 11201, USA, 13 Alabama State University - PhD Program in Microbiology, 325, Montgomery, AL 36101-0271, USA, 14 University of Washington, Department of Periodontology, Seattle, WA 98105, USA, 15 Universitaet des Saarlandes - Biologische Experimentalphysic, Saarbruecken, D-66041 Germany, 16 The University of Texas Medical Branch - Sealy Center for Structural Biology and Molecular Biophysics, Galveston, TX 77204, USA and 17 Max-Planck-Institut - Evolutionsbiologie, Ploen, 24306 Germany Received September 17, 2012; Revised November 19, 2012; Accepted December 6, 2012 ABSTRACT Hybridization of nucleic acids on solid surfaces is a key process involved in high-throughput technologies such as microarrays and, in some cases, next- generation sequencing (NGS). A physical understand- ing of the hybridization process helps to determine the accuracy of these technologies. The goal of a widespread research program is to develop reliable transformations between the raw signals reported by the technologies and individual molecular concen- trations from an ensemble of nucleic acids. This research has inputs from many areas, from bioinfor- matics and biostatistics, to theoretical and experi- mental biochemistry and biophysics, to computer simulations. A group of leading researchers met in Ploen Germany in 2011 to discuss present know- ledge and limitations of our physico-chemical understanding of high-throughput nucleic acid technologies. This meeting inspired us to write this summary, which provides an overview of the state-of-the-art approaches based on physico- chemical foundation to modeling of the nucleic acids hybridization process on solid surfaces. In addition, practical application of current knowledge is emphasized. INTRODUCTION Hybridization of nucleic acids on a solid surface is a key process used in a broad range of technologies. Usually a DNA oligonucleotide (probe) is immobilized on a glass slide or a micrometer-sized bead, with the oligonucleotide acting as a trap for a complementary target sought in a sample. If a complementary target exists in the sample, a duplex is typically formed on binding of the two nucleic *To whom correspondence should be addressed. Tel: +49 4522 763 0; Fax:+49 4522 763 310. Email: alexander.pozhitkov@evolbio.mpg.de Published online 9 January 2013 Nucleic Acids Research, 2013, Vol. 41, No. 5 2779–2796 doi:10.1093/nar/gks1358 ß The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. by guest on June 23, 2016 http://nar.oxfordjournals.org/ Downloaded from