PromoterPredict: sequence-based modelling ofEscherichia coliσ70promoter strength yields logarithmic dependence between promoter strength and sequence

发起人 随机六聚体 生物 RNA聚合酶 序列(生物学) 数学 遗传学 计算生物学 大肠杆菌 分子生物学 基因 基因表达
作者
Ramit Bharanikumar,Keshav Aditya R Premkumar,Ashok Palaniappan
出处
期刊:PeerJ [PeerJ, Inc.]
卷期号:6: e5862-e5862 被引量:18
标识
DOI:10.7717/peerj.5862
摘要

We present PromoterPredict, a dynamic multiple regression approach to predict the strength of Escherichia coli promoters binding the σ 70 factor of RNA polymerase. σ 70 promoters are ubiquitously used in recombinant DNA technology, but characterizing their strength is demanding in terms of both time and money. We parsed a comprehensive database of bacterial promoters for the −35 and −10 hexamer regions of σ 70 -binding promoters and used these sequences to construct the respective position weight matrices (PWM). Next we used a well-characterized set of promoters to train a multivariate linear regression model and learn the mapping between PWM scores of the −35 and −10 hexamers and the promoter strength. We found that the log of the promoter strength is significantly linearly associated with a weighted sum of the −10 and −35 sequence profile scores. We applied our model to 100 sets of 100 randomly generated promoter sequences to generate a sampling distribution of mean strengths of random promoter sequences and obtained a mean of 6E-4 ± 1E-7. Our model was further validated by cross-validation and on independent datasets of characterized promoters. PromoterPredict accepts −10 and −35 hexamer sequences and returns the predicted promoter strength. It is capable of dynamic learning from user-supplied data to refine the model construction and yield more robust estimates of promoter strength. PromoterPredict is available as both a web service ( https://promoterpredict.com ) and standalone tool ( https://github.com/PromoterPredict ). Our work presents an intuitive generalization applicable to modelling the strength of other promoter classes.

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