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QBiC-Pred: quantitative predictions of transcription factor binding changes due to sequence variants.

Abstract：

:Non-coding genetic variants/mutations can play functional roles in the cell by disrupting regulatory interactions between transcription factors (TFs) and their genomic target sites. For most human TFs, a myriad of DNA-binding models are available and could be used to predict the effects of DNA mutations on TF binding. However, information on the quality of these models is scarce, making it hard to evaluate the statistical significance of predicted binding changes. Here, we present QBiC-Pred, a web server for predicting quantitative TF binding changes due to nucleotide variants. QBiC-Pred uses regression models of TF binding specificity trained on high-throughput in vitro data. The training is done using ordinary least squares (OLS), and we leverage distributional results associated with OLS estimation to compute, for each predicted change in TF binding, a P-value reflecting our confidence in the predicted effect. We show that OLS models are accurate in predicting the effects of mutations on TF binding in vitro and in vivo, outperforming widely-used PWM models as well as recently developed deep learning models of specificity. QBiC-Pred takes as input mutation datasets in several formats, and it allows post-processing of the results through a user-friendly web interface. QBiC-Pred is freely available at http://qbic.genome.duke.edu.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Martin V,Zhao J,Afek A,Mielko Z,Gordân R

doi

10.1093/nar/gkz363

subject

Has Abstract

pub_date

2019-07-02 00:00:00

pages

W127-W135

issue

W1

eissn

0305-1048

issn

1362-4962

pii

5494732

journal_volume

47

pub_type

杂志文章

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