Contribution to Structural Integrity: Fatigue and Fracture Related Full Scale Experimental Investigations Carried Out at CSIR-SERC

AbstractCSIR - Structural Engineering Research Centre (CSIR-SERC), Chennai, has state-of-the-art facilities and expertise for carrying out R&D studies in the areas related to fatigue and fracture behaviour of structural components and materials. In the last 25 years, the laboratory has efficiently utilised the facilities and expertise available in serving various institutions and industries related to energy sector, automobile applications, railways, aerospace applications, construction industry etc. Fatigue and fracture studies have been carried out on steel tubular joints of offshore jacket platforms, carbon steel and stainless steel piping components used in power plants, automobile components (connecting rods, air springs, air suspension systems, industrial and automobile chains, stabiliser legs, hub brackets, sub-frames, rubber bushes, parallel link brackets etc.), tyre curing press, alumino-thermit and flash-butt welded rail joints used in Indian Railways, reinforcing bars (thermo-mechanically treated bars, corrosion resistant steel etc.), and many other components and materials. This paper describes some of the important investigations carried out in the Fatigue and Fracture Laboratory (FFL) of CSIR-SERC and presents some salient test results

CytoPred: a server for prediction and classification of cytokines

Cytokines are messengers of immune system. They are small secreted proteins that mediate and regulate the immune system, inflammation and hematopoiesis. Recent studies have revealed important roles played by the cytokines in adjuvants as therapeutic targets and in cancer therapy. In this paper, an attempt has been made to predict this important class of proteins and classify further them into families and subfamilies. A PSI-BLAST+Support Vector Machine-based hybrid approach is adopted to develop the prediction methods. CytoPred is capable of predicting cytokines with an accuracy of 98.29%. The overall accuracy of classification of cytokines into four families and further classification into seven subfamilies is 99.77 and 97.24%, respectively. It has been shown by comparison that CytoPred performs better than the already existing CTKPred. A user-friendly server CytoPred has been developed and available at http://www.imtech.res.in/raghava/cytopred

Prediction and classification of chemokines and their receptors

Chemokines are low molecular mass cytokine-like proteins that orchestrate myriads of immune functions like leukocyte trafficking, T cell differentiation, angiogenesis, hematopeosis and mast cell degranulation. Chemokines also play a role as HIV-1 inhibitor and act as potent natural adjuvant in antitumor immunotherapy. Receptors for these molecules are all seven-pass transmembrane G-protein-coupled receptors that are intimately involved with chemokines in a wide array of physiological and pathological conditions. These receptors also have a major role as co-receptors for HIV-1 entry into target cells. Therefore, chemokine receptors have proven to be excellent targets for small molecule in pharmaceutical industry. The immense importance of chemokines and their receptors motivated us to develop a support vector machine-based method ChemoPred to predict this important class of proteins and further classify them into subfamilies. ChemoPred is capable of predicting chemokines and chemokine receptors with an accuracy of 95.08% and 92.19%, respectively. The overall accuracy of classification of chemokines into three subfamilies was 96.00% and that of chemokine receptors into three families was 92.87%. The server ChemoPred is freely available at www.imtech.res.in/raghava/chemopred

SVM based method for predicting HLA-DRB1<SUP>&#8727;</SUP>0401 binding peptides in an antigen sequence

Summary: Prediction of peptides binding with MHC class II allele HLA-DRB10401 can effectively reduce the number of experiments required for identifying helper T cell epitopes.This paper describes support vector machine (SVM) based method developed for identifying HLA-DRB1&#8727;0401 binding peptides in an antigenic sequence. SVM was trained and tested on large and clean data set consisting of 567 binders and equal number of non-binders. The accuracy of the method was 86% when evaluated through 5-fold cross-validation technique. Available: A web server HLA-DR4Pred based on above approach is available at http://www.imtech.res.in/raghava/ hladr4pred/ and http://bioinformatics.uams.edu/mirror/ ladr4pred/ (Mirror Site)

A neural network method for prediction of β-turn types in proteins using evolutionary information

Motivation: The prediction of β-turns is an important element of protein secondary structure prediction. Recently, a highly accurate neural network based method Betatpred2 has been developed for predicting β-turns in proteins using position-specific scoring matrices (PSSM) generated by PSI-BLAST and secondary structure information predicted by PSIPRED. However, the major limitation of Betatpred2 is that it predicts only β-turn and non-β-turn residues and does not provide any information of different β-turn types. Thus, there is a need to predict β-turn types using an approach based on multiple sequence alignment, which will be useful in overall tertiary structure prediction. Results: In the present work, a method has been developed for the prediction of β-turn types I, II, IV and VIII. For each turn type, two consecutive feed-forward back-propagation networks with a single hidden layer have been used where the first sequence-to-structure network has been trained on single sequences as well as on PSI-BLAST PSSM. The output from the first network along with PSIPRED predicted secondary structure has been used as input for the second-level structure-to-structure network. The networks have been trained and tested on a non-homologous dataset of 426 proteins chains by 7-fold cross-validation. It has been observed that the prediction performance for each turn type is improved significantly by using multiple sequence alignment. The performance has been further improved by using a second level structure-to-structure network and PSIPRED predicted secondary structure information. It has been observed that Type I and II β-turns have better prediction performance than Type IV and VIII β-turns. The final network yields an overall accuracy of 74.5, 93.5, 67.9 and 96.5% with MCC values of 0.29, 0.29, 0.23 and 0.02 for Type I, II, IV and VIII β-turns, respectively, and is better than random prediction. Availability: A web server for prediction of β-turn types I, II, IV and VIII based on above approach is available at http://www.imtech.res.in/raghava/betaturns/ and http://bioinformatics.uams.edu/mirror/betaturns/ (mirror site)

ProPred1: prediction of promiscuous MHC class-I binding sites

ProPred1 is an on-line web tool for the prediction of peptide binding to MHC class-I alleles. This is a matrix-based method that allows the prediction of MHC binding sites in an antigenic sequence for 47 MHC class-I alleles. The server represents MHC binding regions within an antigenic sequence in user-friendly formats. These formats assist user in the identification of promiscuous MHC binders in an antigen sequence that can bind to large number of alleles. ProPred1 also allows the prediction of the standard proteasome and immunoproteasome cleavage sites in an antigenic sequence. This server allows identification of MHC binders, who have the cleavage site at the C terminus. The simultaneous prediction of MHC binders and proteasome cleavage sites in an antigenic sequence leads to the identification of potential T-cell epitopes. Availability: Server is available at http://www.imtech.res. in/raghava/propred1/. Mirror site of this server is available at http://bioinformatics.uams.edu/mirror/propred1/

GWFASTA: server for FASTA search in eukaryotic and microbial genomes

Similarity searches are a powerful method for solving important biological problems such as database scanning, evolutionary studies, gene prediction, and protein structure prediction. FASTA is a widely used sequence comparison tool for rapid database scanning. Here we describe the GWFASTA server that was developed to assist the FASTA user in similarity searches against partially and/or completely sequenced genomes. GWFASTA consists of more than 60 microbial genomes, eight eukaryote genomes, and proteomes of annotatedgenomes. Infact, it provides the maximum number of databases for similarity searching from a single platform. GWFASTA allows the submission of more than one sequence as a single query for a FASTA search. It also provides integrated post-processing of FASTA output, including compositional analysis of proteins, multiple sequences alignment, and phylogenetic analysis. Furthermore, it summarizes the search results organism-wise for prokaryotes and chromosome-wise for eukaryotes. Thus, the integration of different tools for sequence analyses makes GWFASTA a powerful toolfor biologists

Prediction of continuous B-cell epitopes in an antigen using recurrent neural network

B-cell epitopes play a vital role in the development of peptide vaccines, in diagnosis of diseases, and also for allergy research. Experimental methods used for characterizing epitopes are time consuming and demand large resources. The availability of epitope prediction method(s) can rapidly aid experimenters in simplifying this problem. The standard feed-forward (FNN) and recurrent neural network (RNN) have been used in this study for predicting B-cell epitopes in an antigenic sequence. The networks have been trained and tested on a clean data set, which consists of 700 non-redundant B-cell epitopes obtained from Bcipep database and equal number of non-epitopes obtained randomly from Swiss-Prot database. The networks have been trained and tested at different input window length and hidden units. Maximum accuracy has been obtained using recurrent neural network (Jordan network) with a single hidden layer of 35 hidden units for window length of 16. The final network yields an overall prediction accuracy of 65.93% when tested by fivefold cross-validation. The corresponding sensitivity, specificity, and positive prediction values are 67.14, 64.71, and 65.61%, respectively. It has been observed that RNN (JE) was more successful than FNN in the prediction of B-cell epitopes. The length of the peptide is also important in the prediction of B-cell epitopes from antigenic sequences. The webserver ABCpred is freely available at www.imtech.res.in/raghava/abcpred/

GPCRsclass: a web tool for the classification of amine type of G-protein-coupled receptors

The receptors of amine subfamily are specifically major drug targets for therapy of nervous disorders and psychiatric diseases. The recognition of novel amine type of receptors and their cognate ligands is of paramount interest for pharmaceutical companies. In the past, Chou and co-workers have shown that different types of amine receptors are correlated with their amino acid composition and are predictable on its basis with considerable accuracy [Elrod and Chou (2002) Protein Eng., 15, 713–715]. This motivated us to develop a better method for the recognition of novel amine receptors and for their further classification. The method was developed on the basis of amino acid composition and dipeptide composition of proteins using support vector machine. The method was trained and tested on 167 proteins of amine subfamily of G-protein-coupled receptors (GPCRs). The method discriminated amine subfamily of GPCRs from globular proteins with Matthew's correlation coefficient of 0.98 and 0.99 using amino acid composition and dipeptide composition, respectively. In classifying different types of amine receptors using amino acid composition and dipeptide composition, the method achieved an accuracy of 89.8 and 96.4%, respectively. The performance of the method was evaluated using 5-fold cross-validation. The dipeptide composition based method predicted 67.6% of protein sequences with an accuracy of 100% with a reliability index ≥5. A web server GPCRsclass has been developed for predicting amine-binding receptors from its amino acid sequence [ and (mirror site)]