Subtractive SELEX against two heterogeneous target samples: Numerical simulations and analysis

Chen, Chi-Kan; Kuo, Tzy-Ling; Chan, Po-Chou; Lin, Lung-Ying

doi:10.1016/j.compbiomed.2006.06.015

Cited by 17 publications

(19 citation statements)

References 16 publications

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“…The subpooling method requires N M subpools yielding N M equations, where N is the number of subpools of nucleic acids and M is the number of targets. Instead, the authors in [7] and [8] suggested a condensed subpooling method. With this method, the size of nucleic acid subpools can be reduced optimally to N × M instead of N M .…”

Section: Mathematical Models For Selexmentioning

confidence: 99%

“…In many cases, however, most target molecules, including proteins, have multiple binding sites, and all their interactions can be considered specific and saturable 8 . Moreover, some targets may not be purified or may be included with other target species in a mixture, so it can be difficult to obtain a desired single target component of interest from a mixture with multiple target species.…”

Section: Mathematical Models For Selexmentioning

confidence: 99%

“…These quantities of efficiencies are important thermodynamic parameters and are also referred to as binding probabilities ( [8]) or as a measure of thermodynamic free energy 2 or chemical potential. We will discuss the relationship between chemical potentials and equilibrium constants or overall efficiencies of these reactions later.…”

Section: Overall Dissociation and Association Constants And Efficienciesmentioning

confidence: 99%

“…By alternating the two processes, we obtain a refined population of nucleic acids, and this results in selectivity and specificity. See [8], [12] and [30] for various aspects of performing the negative selection processes. (The SE-LEX procedure that involves negative selection (or subtractive selection) is also referred to as subtractive SELEX.)…”

Section: Stability Properties Of Stationary Solutionsmentioning

confidence: 99%

“…to free j th NA, [N Af j ], can be measured from the gel shift experiment ( [26]) and defined as 8) where the equation (2.3) is used to express in term of concentrations of the free targets. We also define the fraction F j of nucleic acid N A j as…”

Section: Formulation Of the Selection Processmentioning

confidence: 99%

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A Mathematical Analysis of Multiple-Target Selex

et al. 2010

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Section: Mathematical Models For Selexmentioning

confidence: 99%

Section: Mathematical Models For Selexmentioning

confidence: 99%

Section: Overall Dissociation and Association Constants And Efficienciesmentioning

confidence: 99%

Section: Stability Properties Of Stationary Solutionsmentioning

confidence: 99%

Section: Formulation Of the Selection Processmentioning

confidence: 99%

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A Mathematical Analysis of Multiple-Target Selex

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In silico design of novel aptamers utilizing a hybrid method of machine learning and genetic algorithm

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A Computational Study of Alternate SELEX

2014

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Systematic evolution of ligands by exponential enrichment (SELEX) is a procedure for identifying nucleic acid (NA) molecules with affinities for specific target species, such as proteins, peptides, or small organic molecules. Here, we extend the work in Seo et al. (Bull Math Biol 72:1623-1665, 2010) (multiple-target SELEX or positive SELEX) and examine an alternate SELEX process with multiple targets by incorporating negative selection into a positive SELEX protocol. The alternate SELEX process is done iteratively by alternating several positive selection rounds with several negative selection rounds. At the end of each positive selection round, NAs are eluted from the bound product and amplified by polymerase chain reaction (PCR) to increase the size of the pool of NA species that bind preferentially to the given positive target vector. The enriched population of NAs is then exposed to the negative targets (undesired targets). The free NA species (instead of the bound NA species being eluted) are retained and amplified by PCR (negative selection). The goal is to minimize an enrichment of nonspecifically binding NAs against multiple targets. While positive selection alone results in a pool of NAs that bind tightly to a given target vector, negative selection results in the subset of the NAs that bind best to the nontarget vectors that are also present. By alternating the two processes, we eventually obtain a refined population of nucleic acids that bind to the desired target(s) with high "selectivity" and "specificity." In the present paper, we give formulations of the negative and alternate selection processes and define their efficiencies in a meaningful way. We study the asymptotic behavior of alternate SELEX system as a discrete-time dynamical system. To do this, we use the chemical potential to examine how alternate SELEX leads to the selection of NAs with more specific interactions when the ratio of the number of positive selection rounds to the number of negative selection rounds is fixed. Alternate SELEX is said to be globally asymptotically stable if, given the initial target vector and a fixed ratio, the distribution of the limiting NA fractions does not depend on the relative concentrations of the NAs in the initial pool (provided that all of the NA species are initially present in the initial pool). We state conditions on the matrix of NA-target affinities that determine when the alternate SELEX process is globally asymptotically stable in this sense and illustrate these results computationally.

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Subtractive SELEX against two heterogeneous target samples: Numerical simulations and analysis

Cited by 17 publications

References 16 publications

A Mathematical Analysis of Multiple-Target Selex

A Mathematical Analysis of Multiple-Target Selex

In silico design of novel aptamers utilizing a hybrid method of machine learning and genetic algorithm

A Computational Study of Alternate SELEX

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