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September 2012 A model for sequential evolution of ligands by exponential enrichment (SELEX) data
Juli Atherton, Nathan Boley, Ben Brown, Nobuo Ogawa, Stuart M. Davidson, Michael B. Eisen, Mark D. Biggin, Peter Bickel
Ann. Appl. Stat. 6(3): 928-949 (September 2012). DOI: 10.1214/12-AOAS537

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.

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Juli Atherton. Nathan Boley. Ben Brown. Nobuo Ogawa. Stuart M. Davidson. Michael B. Eisen. Mark D. Biggin. Peter Bickel. "A model for sequential evolution of ligands by exponential enrichment (SELEX) data." Ann. Appl. Stat. 6 (3) 928 - 949, September 2012. https://doi.org/10.1214/12-AOAS537

Information

Published: September 2012
First available in Project Euclid: 31 August 2012

zbMATH: 1254.92025
MathSciNet: MR3012515
Digital Object Identifier: 10.1214/12-AOAS537

Keywords: SELEX , transcription factor binding

Rights: Copyright © 2012 Institute of Mathematical Statistics

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Vol.6 • No. 3 • September 2012
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