Modeling and global optimization of DNA separation

We develop a non-convex non-linear programming problem that determines the minimum run time to resolve different lengths of DNA using a gel-free micelle end-labeled free solution electrophoresis separation method. Our optimization framework allows for efficient determination of the utility of different DNA separation platforms and enables the identification of the optimal operating conditions for these DNA separation devices. The non-linear programming problem requires a model for signal spacing and signal width, which is known for many DNA separation methods. As a case study, we show how our approach is used to determine the optimal run conditions for micelle end-labeled free-solution electrophoresis and examine the trade-offs between a single capillary system and a parallel capillary system. Parallel capillaries are shown to only be beneficial for DNA lengths above 230 bases using a polydisperse micelle end-label otherwise single capillaries produce faster separations.

[1]  J. Viovy Electrophoresis of DNA and other polyelectrolytes: Physical mechanisms , 2000 .

[2]  Thomas N. Chiesl,et al.  Ultrafast DNA sequencing on a microchip by a hybrid separation mechanism that gives 600 bases in 6.5 minutes , 2008, Proceedings of the National Academy of Sciences.

[3]  Nikolaos V. Sahinidis,et al.  A polyhedral branch-and-cut approach to global optimization , 2005, Math. Program..

[4]  R. Braatz,et al.  Globally optimal robust process control , 1999 .

[5]  Edward M. B. Smith,et al.  Global optimisation of nonconvex MINLPs , 1997 .

[6]  C. Floudas,et al.  Global optimization in the 21st century: Advances and challenges , 2005, Computers and Chemical Engineering.

[7]  F. Oaks,et al.  Separating DNA sequencing fragments without a sieving matrix , 1999, Electrophoresis.

[8]  J. Butler,et al.  Forensic DNA Typing: Biology and Technology behind STR Markers , 2002, Heredity.

[9]  C. Desruisseaux,et al.  Electrophoresis of Composite Molecular Objects. 1. Relation between Friction, Charge, and Ionic Strength in Free Solution , 2000 .

[10]  D. Shah,et al.  Importance of micellar kinetics in relation to technological processes. , 2002, Journal of colloid and interface science.

[11]  Garth P. McCormick,et al.  Computability of global solutions to factorable nonconvex programs: Part I — Convex underestimating problems , 1976, Math. Program..

[12]  Nikolaos V. Sahinidis,et al.  Semidefinite Relaxations of Fractional Programs via Novel Convexification Techniques , 2001, J. Glob. Optim..

[13]  Shane T. Grosser,et al.  Identification of PCR products using PNA amphiphiles in micellar electrokinetic chromatography. , 2007, Analytical Chemistry.

[14]  J. Calvin Giddings,et al.  Unified Separation Science , 1991 .

[15]  Jeffrey C. Lagarias,et al.  Convergence Properties of the Nelder-Mead Simplex Method in Low Dimensions , 1998, SIAM J. Optim..

[16]  B. Zimm Dynamics of Polymer Molecules in Dilute Solution: Viscoelasticity, Flow Birefringence and Dielectric Loss , 1956 .

[17]  L. Aaltonen,et al.  MSH2 and MLH1 mutations in sporadic replication error‐positive colorectal carcinoma as assessed by two‐dimensional DNA electrophoresis , 1997, Genes, chromosomes & cancer.

[18]  Louisa Alfazema Capillary Electrophoresis: Theory and Practice. P. Camilleri, editor , 2000 .

[19]  P. Mukerjee Size distribution of small and large micelles. Multiple equilibrium analysis , 1972 .

[20]  Caspar Zialor DNA sequencing with chain terminating inhibitors , 2014 .

[21]  Theoretical studies of DNA during gel electrophoresis. , 1989, Science.

[22]  A. J. Pfeiffer,et al.  Design and Optimization of Compact Microscale Electrophoretic Separation Systems , 2004 .

[23]  Douglas R Tree,et al.  Beyond gel electrophoresis: microfluidic separations, fluorescence burst analysis, and DNA stretching. , 2013, Chemical reviews.

[24]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Ignacio E. Grossmann,et al.  A global optimization algorithm for linear fractional and bilinear programs , 1995, J. Glob. Optim..

[26]  John M. Butler,et al.  Forensic DNA typing : biology & technology behind STR markers , 2001 .

[27]  John L. Klepeis,et al.  DIMACS Series in Discrete Mathematicsand Theoretical Computer Science Global Optimization Approaches in Protein Folding andPeptide , 2007 .

[28]  Ignacio E. Grossmann,et al.  Assignment and sequencing models for thescheduling of process systems , 1998, Ann. Oper. Res..

[29]  Shane T. Grosser,et al.  Length‐dependent DNA separations using multiple end‐attached peptide nucleic acid amphiphiles in micellar electrokinetic chromatography , 2008, Electrophoresis.

[30]  Ignacio E. Grossmann,et al.  Global optimization for the synthesis of integrated water systems in chemical processes , 2006, Comput. Chem. Eng..

[31]  A. Barron,et al.  Simultaneous detection of 19 K‐ras mutations by free‐solution conjugate electrophoresis of ligase detection reaction products on glass microchips , 2013, Electrophoresis.

[32]  R. Meagher,et al.  Sequencing of DNA by free-solution capillary electrophoresis using a genetically engineered protein polymer drag-tag. , 2008, Analytical chemistry.

[33]  N. Stellwagen,et al.  The free solution mobility of DNA. , 1997, Biopolymers.

[34]  N. Sahinidis,et al.  A Lagrangian Approach to the Pooling Problem , 1999 .

[35]  K. I. M. McKinnon,et al.  A Generic Global Optimization Algorithm for the Chemical and Phase Equilibrium Problem , 1998, J. Glob. Optim..

[36]  Yining Shi DNA sequencing and multiplex STR analysis on plastic microfluidic devices , 2006, Electrophoresis.

[37]  Hanif D. Sherali,et al.  A global optimization algorithm for polynomial programming problems using a Reformulation-Linearization Technique , 1992, J. Glob. Optim..

[38]  Nikolaos V. Sahinidis,et al.  Convexification and Global Optimization in Continuous and Mixed-Integer Nonlinear Programming , 2002 .

[39]  P. Joos,et al.  Rate of demicellization from the dynamic surface tensions of micellar solutions , 1982 .

[40]  P. E. Rouse A Theory of the Linear Viscoelastic Properties of Dilute Solutions of Coiling Polymers , 1953 .

[41]  L. B. Diego,et al.  High‐performance capillary electrophoretic method for the quantification of 5‐methyl 2'‐deoxycytidine in genomic DNA: Application to plant, animal and human cancer tissues , 2002, Electrophoresis.

[42]  Linus Schrage,et al.  The global solver in the LINDO API , 2009, Optim. Methods Softw..

[43]  Joel C. Colburn,et al.  Capillary electrophoresis : theory & practice , 1992 .

[44]  James E. Falk,et al.  Jointly Constrained Biconvex Programming , 1983, Math. Oper. Res..

[45]  A. Neumaier,et al.  A global optimization method, αBB, for general twice-differentiable constrained NLPs — I. Theoretical advances , 1998 .