The Annals of Applied Statistics

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, and Peter Bickel

Full-text: Open access

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.

Article information

Source
Ann. Appl. Stat., Volume 6, Number 3 (2012), 928-949.

Dates
First available in Project Euclid: 31 August 2012

Permanent link to this document
https://projecteuclid.org/euclid.aoas/1346418568

Digital Object Identifier
doi:10.1214/12-AOAS537

Mathematical Reviews number (MathSciNet)
MR3012515

Zentralblatt MATH identifier
1254.92025

Keywords
SELEX transcription factor binding

Citation

Atherton, Juli; Boley, Nathan; Brown, Ben; Ogawa, Nobuo; Davidson, Stuart M.; Eisen, Michael B.; Biggin, Mark D.; Bickel, Peter. A model for sequential evolution of ligands by exponential enrichment (SELEX) data. Ann. Appl. Stat. 6 (2012), no. 3, 928--949. doi:10.1214/12-AOAS537. https://projecteuclid.org/euclid.aoas/1346418568


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Supplemental materials

  • Supplementary material: Code for SELEX model. The code for the SELEX model used in the application of this paper is available at the above url. Extra simulations, mentioned in Section 5.1, are also provided as supplementary material.