An ANFIS approach to transmembrane protein prediction

This paper is concerned with transmembrane prediction analysis. Most of novel drug design requires the use of Membrane proteins. Transmembrane protein structure allows pharmaceutical industry to design new drugs based on structural layout. However, laboratory experimental structure determination by X-ray crystallography is difficult to be achieved as the hydrophobic molecules do not crystalize easily. Moreover, the sheer number of proteins demands a computational solution to transmembrane regions identifications. This research therefore presents a novel Adaptive Neural Fuzzy Inference System (ANFIS) approach to predict and analyze of membrane helices in amino acid sequences. The ANFIS technique is implemented to predict membrane helices using sliding window data capturing. The paper uses hydrophobicity and propensity to encode the datasets using the conventional one letter symbol of amino acid residues. The computer simulation results show that the offered ANFIS methodology predicts transmembrane regions with high accuracy for randomly selected proteins

NN approach and its comparison with NN-SVM to beta-barrel prediction

This paper is concerned with applications of a dual Neural Network (NN) and Support Vector Machine (SVM) to prediction and analysis of beta barrel trans membrane proteins. The prediction and analysis of beta barrel proteins usually offer a host of challenges to the research community, because of their low presence in genomes. Current beta barrel prediction methodologies present intermittent misclassifications resulting in mismatch in the number of membrane spanning regions within amino-acid sequences. To address the problem, this research embarks upon a NN technique and its comparison with hybrid- two-level NN-SVM methodology to classify inter-class and intra-class transitions to predict the number and range of beta membrane spanning regions. The methodology utilizes a sliding-window-based feature extraction to train two different class transitions entitled symmetric and asymmetric models. In symmet- ric modelling, the NN and SVM frameworks train for sliding window over the same intra-class areas such as inner-to-inner, membrane(beta)-to-membrane and outer-to-outer. In contrast, the asymmetric transi- tion trains a NN-SVM classifier for inter-class transition such as outer-to-membrane (beta) and membrane (beta)-to-inner, inner-to-membrane and membrane-to-outer. For the NN and NN-SVM to generate robust outcomes, the prediction methodologies are analysed by jack-knife tests and single protein tests. The computer simulation results demonstrate a significant impact and a superior performance of NN-SVM tests with a 5 residue overlap for signal protein over NN with and without redundant proteins for pre- diction of trans membrane beta barrel spanning regions

Cascading classifier application for topology prediction of transmembrane beta-barrel proteins

Membrane proteins are a major focus for new drug discovery. Transmembrane beta-barrel proteins play key roles in the translocation machinery, pore formation, membrane anchoring and ion exchange. Given their key roles and the difficulty in membrane protein structure determination, the use of computational modelling is essential. This paper focuses on the topology prediction of transmembrane beta-barrel proteins. In the field of bioinformatics, many years of research has been spent on the topology prediction of transmembrane alpha-helices. The efforts to TMB (transmembrane beta-barrel) proteins topology prediction have been overshadowed and the prediction accuracy could be improved with further research. Various methodologies have been developed in the past for the prediction of TMB proteins topology, however the use of cascading classifier has never been fully explored. This research presents a novel approach to TMB topology prediction with the use of a cascading classifier. The MATLAB computer simulation results show that the proposed methodology predicts transmembrane beta-barrel proteins topologies with high accuracy for randomly selected proteins. By using the cascading classifier approach the best overall accuracy is 76.3% with a precision of 0.831 and recall or probability of detection of 0.799 for TMB topology prediction. The accuracy of 76.3% is achieved using a two-layers cascading classifier

Signal peptide discrimination and cleavage site identification using SVM and NN

About 15% of all proteins in a genome contain a signal peptide (SP) sequence, at the N-terminus, that targets the protein to intracellular secretory pathways. Once the protein is targeted correctly in the cell, the SP is cleaved, releasing the mature protein. Accurate prediction of the presence of these short aminoacid SP chains is crucial for modelling the topology of membrane proteins, since SP sequences can be confused with transmembrane domains due to similar composition of hydrophobic amino acids. This paper presents a cascaded Support Vector Machine (SVM)-Neural Network (NN) classification methodology for SP discrimination and cleavage site identification. The proposed method utilises a dual phase classification approach using SVM as a primary classifier to discriminate SP sequences from Non-SP. The methodology further employs NNs to predict the most suitable cleavage site candidates. In phase one, a SVM classification utilises hydrophobic propensities as a primary feature vector extraction using symmetric sliding window amino-acid sequence analysis for discrimination of SP and Non-SP. In phase two, a NN classification uses asymmetric sliding window sequence analysis for prediction of cleavage site identification. The proposed SVM-NN method was tested using Uni-Prot non-redundant datasets of eukaryotic and prokaryotic proteins with SP and Non-SP N-termini. Computer simulation results demonstrate an overall accuracy of 0.90 for SP and Non-SP discrimination based on Matthews Correlation Coefficient (MCC) tests using SVM. For SP cleavage site prediction, the overall accuracy is 91.5% based on cross-validation tests using the novel SVM-NN model

Machine learning applications for the topology prediction of transmembrane beta-barrel proteins

The research topic for this PhD thesis focuses on the topology prediction of beta-barrel transmembrane proteins. Transmembrane proteins adopt various conformations that are about the functions that they provide. The two most predominant classes are alpha-helix bundles and beta-barrel transmembrane proteins. Alpha-helix proteins are present in larger numbers than beta-barrel transmembrane proteins in structure databases. Therefore, there is a need to find computational tools that can predict and detect the structure of beta-barrel transmembrane proteins. Transmembrane proteins are used for active transport across the membrane or signal transduction. Knowing the importance of their roles, it becomes essential to understand the structures of the proteins. Transmembrane proteins are also a significant focus for new drug discovery. Transmembrane beta-barrel proteins play critical roles in the translocation machinery, pore formation, membrane anchoring, and ion exchange. In bioinformatics, many years of research have been spent on the topology prediction of transmembrane alpha-helices. The efforts to TMB (transmembrane beta-barrel) proteins topology prediction have been overshadowed, and the prediction accuracy could be improved with further research. Various methodologies have been developed in the past to predict TMB proteins topology. Methods developed in the literature that are available include turn identification, hydrophobicity profiles, rule-based prediction, HMM (Hidden Markov model), ANN (Artificial Neural Networks), radial basis function networks, or combinations of methods. The use of cascading classifier has never been fully explored. This research presents and evaluates approaches such as ANN (Artificial Neural Networks), KNN (K-Nearest Neighbors, SVM (Support Vector Machines), and a novel approach to TMB topology prediction with the use of a cascading classifier. Computer simulations have been implemented in MATLAB, and the results have been evaluated. Data were collected from various datasets and pre-processed for each machine learning technique. A deep neural network was built with an input layer, hidden layers, and an output. Optimisation of the cascading classifier was mainly obtained by optimising each machine learning algorithm used and by starting using the parameters that gave the best results for each machine learning algorithm. The cascading classifier results show that the proposed methodology predicts transmembrane beta-barrel proteins topologies with high accuracy for randomly selected proteins. Using the cascading classifier approach, the best overall accuracy is 76.3%, with a precision of 0.831 and recall or probability of detection of 0.799 for TMB topology prediction. The accuracy of 76.3% is achieved using a two-layers cascading classifier. By constructing and using various machine-learning frameworks, systems were developed to analyse the TMB topologies with significant robustness. We have presented several experimental findings that may be useful for future research. Using the cascading classifier, we used a novel approach for the topology prediction of TMB proteins