Enhanced identification of β-lactamases and its classes using sequence, physicochemical and evolutionary information with sequence feature characterization of the classes. (June 2017)

• Record Type: Journal Article
• Authors: Nath, Abhigyan; Karthikeyan, S.
• Is Part Of: Computational biology and chemistry. Volume 68(2017)
• Page Start: 29
• Page End: 38
• Publication Date: 2017-06
• Subjects: β-Lactamases -- Physicochemical properties -- Dipeptide counts -- PSSM -- Average one dependence estimator; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2017.02.006
• Languages: English
• ISSNs: 1476-9271

Abstract

Graphical abstract: Highlights: Enhanced classification of β lactamases and its classes. Extraction of significant sequence and physicochemical property differences between the different classes of β lactamases. Some interesting differences in dipeptide counts are also reported. Abstract: β-lactamases provides one of the most successful means of evading the therapeutic effects of β lactam class of antibiotics by many gram positive and gram negative bacteria. On the basis of sequence identity, β-lactamases have been identified into four distinct classes- A, B, C and D. The classes A, C and D are the serine β-lactamases and class B is the metallo-lactamse. In the present study, we developed a two stage cascade classification system. The first-stage performs the classification of β-lactamases from non-β-lactamases and the second-stage performs the further classification of β-lactamases into four different β–lactamase classes. In the first-stage binary classification, we obtained an accuracy of 97.3% with a sensitivity of 89.1% and specificity of 98.0% and for the second stage multi-class classification, we obtained an accuracy of 87.3% for the class A, 91.0% for the class B, 96.3% for the class C and 96.4% for class D. A systematic statistical analysis is carried out on the sieved-out, correctly-predicted instances from the second stage classifier, which revealed some interesting patterns. We analyzed different classes of β-lactamases on the basis of sequence and physicochemical property differences between them. Among amino acid composition, H, W, Y and V showed significant differences between the different β-lactamases classes. Differences in average physicochemical properties are observed for isoelectric point, volume, flexibility, hydrophobicity, bulkiness and charge in one or more β-lactamase classes. The key differences in physicochemical property groups can be observed in small and aromatic groups. Among amino acid property group n-grams except charged n-grams, all other property group n-grams are significant in one or more classes. Statistically significant differences in dipeptide counts among different β-lactamase classes are also reported.