dorsal/arxiv
View SchemaQuantitative modeling and data analysis of SELEX experiments
| Authors | Marko Djordjevic, Anirvan M. Sengupta |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0512001 |
| URL | https://arxiv.org/abs/q-bio/0512001 |
| DOI | 10.1088/1478-3975/3/1/002 |
Abstract
SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is an experimental procedure that allows extracting, from an initially random pool of DNA, those oligomers with high affinity for a given DNA-binding protein. We address what is a suitable experimental and computational procedure to infer parameters of transcription factor-DNA interaction from SELEX experiments. To answer this, we use a biophysical model of transcription factor-DNA interactions to quantitatively model SELEX. We show that a standard procedure is unsuitable for obtaining accurate interaction parameters. However, we theoretically show that a modified experiment in which chemical potential is fixed through different rounds of the experiment allows robust generation of an appropriate data set. Based on our quantitative model, we propose a novel bioinformatic method of data analysis for such modified experiment and apply it to extract the interaction parameters for a mammalian transcription factor CTF/NFI. From a practical point of view, our method results in a significantly improved false positive/false negative trade-off, as compared to both the standard information theory based method and a widely used empirically formulated procedure.
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"abstract": "SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is an\nexperimental procedure that allows extracting, from an initially random pool of\nDNA, those oligomers with high affinity for a given DNA-binding protein. We\naddress what is a suitable experimental and computational procedure to infer\nparameters of transcription factor-DNA interaction from SELEX experiments. To\nanswer this, we use a biophysical model of transcription factor-DNA\ninteractions to quantitatively model SELEX. We show that a standard procedure\nis unsuitable for obtaining accurate interaction parameters. However, we\ntheoretically show that a modified experiment in which chemical potential is\nfixed through different rounds of the experiment allows robust generation of an\nappropriate data set. Based on our quantitative model, we propose a novel\nbioinformatic method of data analysis for such modified experiment and apply it\nto extract the interaction parameters for a mammalian transcription factor\nCTF/NFI. From a practical point of view, our method results in a significantly\nimproved false positive/false negative trade-off, as compared to both the\nstandard information theory based method and a widely used empirically\nformulated procedure.",
"arxiv_id": "q-bio/0512001",
"authors": [
"Marko Djordjevic",
"Anirvan M. Sengupta"
],
"categories": [
"q-bio.GN"
],
"doi": "10.1088/1478-3975/3/1/002",
"title": "Quantitative modeling and data analysis of SELEX experiments",
"url": "https://arxiv.org/abs/q-bio/0512001"
},
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