A model for sequential evolution of ligands by exponential enrichment (SELEX) data

DOI10.1214/12-AOAS537MaRDI QIDQ714351zbMATH OpenOpenAlexWikidataFDO

Authors Juli Atherton, Nathan Boley, Ben Brown, Nobuo Ogawa, Stuart M. Davidson, Michael B. Eisen, Mark D. Biggin, P. J. Bickel

Publication date 21 October 2012

Published in The Annals of Applied Statistics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1205.1819, https://projecteuclid.org/euclid.aoas/1346418568

zbMATH Keywords

transcription factor binding

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Biochemistry, molecular biology (92C40) Probabilistic models, generic numerical methods in probability and statistics (65C20)

Abstract: A Systematic Evolution of Ligands by EXponential enrichment (SELEX) experiment begins in round one with a random pool of oligonucleotides in equilibrium solution with a target. Over a few rounds, oligonucleotides having a high affinity for the target are selected. Data from a high throughput SELEX experiment consists of lists of thousands of oligonucleotides sampled after each round. Thus far, SELEX experiments have been very good at suggesting the highest affinity oligonucleotide, but modeling lower affinity recognition site variants has been difficult. Furthermore, an alignment step has always been used prior to analyzing SELEX data. We present a novel model, based on a biochemical parametrization of SELEX, which allows us to use data from all rounds to estimate the affinities of the oligonucleotides. Most notably, our model also aligns the oligonucleotides. We use our model to analyze a SELEX experiment containing double stranded DNA oligonucleotides and the transcription factor Bicoid as the target. Our SELEX model outperformed other published methods for predicting putative binding sites for Bicoid as indicated by the results of an in-vivo ChIP-chip experiment.

Recommendations

• A mathematical analysis of SELEX
• A computational study of alternate SELEX
• A discrete dynamical system arising in molecular biology
• A mathematical analysis of multiple-target SELEX
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Cites work

• scientific article; zbMATH DE number 5060482 (Why is no real title available?)
• A Simplex Method for Function Minimization
• A model for sequential evolution of ligands by exponential enrichment (SELEX) data
• An efficient method for finding the minimum of a function of several variables without calculating derivatives

Cited in

(10)

• Estimation of statistical binding properties of ligand population during in vitro selection based on population dynamics theory
• A model for sequential evolution of ligands by exponential enrichment (SELEX) data
• High affinity extremes in combinatorial libraries and repertoires
• A discrete dynamical system arising in molecular biology
• A computational study of alternate SELEX
• A mathematical analysis of multiple-target SELEX
• Selective phenome growth adapted \(N K\) model: a novel landscape to represent aptamer ligand binding
• Discrete dynamical systems in multiple target and alternate SELEX
• Statistical methods for estimating complexity from competition experiments between two populations
• A mathematical analysis of SELEX

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