PredCRP: predicting and analysing the regulatory roles of CRP from its binding sites in Escherichia coli

Abstract

Cyclic AMP receptor protein (CRP), a global regulator in Escherichia coli, regulates more than 180 genes via two roles: activation and repression. Few methods are available for predicting the regulatory roles from the binding sites of transcription factors. This work proposes an accurate method PredCRP to derive an optimised model (named PredCRP-model) and a set of four interpretable rules (named PredCRP-ruleset) for predicting and analysing the regulatory roles of CRP from sequences of CRP-binding sites. A dataset consisting of 169 CRP-binding sites with regulatory roles strongly supported by evidence was compiled. The PredCRP-model, using 12 informative features of CRP-binding sites, and cooperating with a support vector machine achieved a training and test accuracy of 0.98 and 0.93, respectively. PredCRP-ruleset has two activation rules and two repression rules derived using the 12 features and the decision tree method C4.5. This work further screened and identified 23 previously unobserved regulatory interactions in Escherichia coli. Using quantitative PCR for validation, PredCRP-model and PredCRP-ruleset achieved a test accuracy of 0.96 (=22/23) and 0.91 (=21/23), respectively. The proposed method is suitable for designing predictors for regulatory roles of all global regulators in Escherichia coli. PredCRP can be accessed at https://github.com/NctuICLab/PredCRP.

Metabolic perturbations in mutants of glucose transporters and their applications in metabolite production in Escherichia coli

“…Transcription of all genes of the TCA cycle (gltA, acnAB, icd, sucABCD, sdhAB, frdABCD, fumABC, and mdh) was significantly activated. Given that most of the genes related to the TCA cycle are activated by CRP and Cra, this result corroborates well with the results of preceding studies [38,39]. Downregulation of PEP carboxylase (ppc) and upregulation of PEP carboxykinase (pck) were also in accordance with previous reports that transcription of ppc is repressed by Cra, and that of pck is activated by Cra and CRP [39,40].…”

Transcriptional regulation of fatty acid cis–trans isomerization in the solvent‐tolerant soil bacterium, Pseudomonas putida F1

“…This indicated that Crp2-binding site may play a role in cti regulation in exponential growth phase by a Crp independent mechanism. In agreement with PredCRP-model (Tsai et al, 2018), our data showed that Crp represses cti expression. However, our EMSA results suggested that only the Crp1 site located distal downstream of cti promoter sequences is necessary for Crp binding, highlighting the importance of validation of the in-silico studies by experimental assays.…”

“…The Crp2‐binding region was located just downstream of the RNA polymerase −35 binding site of cti ‐279 promoter. Similar Crp‐binding sites were predicted by PredCRP‐model, which assumes that when Crp binds to these regions, it blocks the transcription process (Tsai et al ., ).…”

“…Our study adds an additional envelope‐associated Crp target in P. putida and indicates that P. putida Crp could be associated with the regulation of cell envelope composition. In addition, our EMSA studies complemented previously reported PredCRP model (Tsai et al ., ), by showing that even in the presence of two putative Crp‐binding sites, only the downstream site is necessary for Crp binding and repression of cti expression (Fig. E).…”

Identifying a miRNA signature for predicting the stage of breast cancer

“…The feature selection algorithm IBCGA uses an intelligent evolutionary algorithm 82 to solve the large parameter optimization problem. IBCGA has been successfully applied in several bioinformatics problems, including the prediction of human ubiquitination sites 83 , the prediction of the regulatory roles of cyclic AMP receptor proteins 84 and the estimation of survival time for cancer patients 85 , 86 .…”