In Silico Biology - Volume 3, issue 4

Authors: Wiezer, Arnim | Merkl, Rainer

Article Type: Research Article

Abstract: secureBLAST supplements NCBI wwwblast with features necessary to control in an easy manageable way usage of BLAST data sets and their update. The concept we implemented allows to offer on a single BLAST server several data sets with individually configurable access rights. Security is provided by user authentication and encryption of the http traffic via SSL. By using secureBLAST, the administration of users and databases can be done via a web interface. Therefore, secureBLAST is valuable …for institutions that have to restrict access to their datasets or just want to administer BLAST servers via a web interface. Show more

Keywords: wwwblast, user authentication, BLAST database management

Citation: In Silico Biology, vol. 3, no. 4, pp. 405-409, 2003

Authors: Petrovsky, Nikolai | Schönbach, Christian | Brusic, Vladimir

Article Type: Research Article

Abstract: Novartis Foundation sponsored a Symposium which brought together a group of experimental immunologists, theoretical immunologists, and bioinformaticians to discuss the new field of immunoinformatics. The discussion focused on immunological databases, antigen processing and presentation, immunogenomics, host-pathogen interactions, and mathematical modelling of the immune system. A main conclusion of the meeting is the critical role played by immunoinformatics in current immunology research. In particular, immunoinformatics provides a foundation for the emerging fields of …systems immunology and immunogenomics. Show more

Keywords: antigen processing, antigen presentation, host-pathogen interactions, immunogenomics, immunoinformatics, immunological databases, mathematical models

Citation: In Silico Biology, vol. 3, no. 4, pp. 411-416, 2003

Authors: Carugo, Oliviero

Article Type: Research Article

Abstract: A method is presented to predict those polypeptide segments within a globular protein that are more likely to be exposed to the solvent. The protein amino acidic sequence is the only information needed by this new algorithm. It uses a consensus hydrophobicity scale, derived from 28 known scales, and it is based on the comparison between the average hydrophobicity of a polypeptide fragment and the average hydrophobicity expected for a segment containing the same number of …residues. The latter values are pre-computed from a non-redundant set of single chain protein structural domains. The comparison between the two average values results in a t value that readily provides the prediction with a statistical significance. A jack-knife validation analysis indicates that the protein segment predicted to be the most solvent exposed is actually solvent exposed and amongst the fragments that are most exposed. The source of a stand-alone program, written in C language, that allows the prediction of the most likely solvent exposed segment in a globular protein is available from the author. Show more

Keywords: accessibility prediction, epitope, hydrophobicity, modelling, protein structure, solvent accessibility, structure prediction

Citation: In Silico Biology, vol. 3, no. 4, pp. 417-428, 2003

Authors: Janaki, Chintalapati | Joshi, Rajendra R.

Article Type: Research Article

Abstract: In the past decade there has been an increase in the number of completely sequenced genomes due to the race of multibillion-dollar genome-sequencing projects. The enormous biological sequence data thus flooding into the sequence databases necessitates the development of efficient tools for comparative genome sequence analysis. The information deduced by such analysis has various applications viz. structural and functional annotation of novel genes and proteins, finding gene order in the genome, gene fusion studies, …constructing metabolic pathways etc. Such study also proves invaluable for pharmaceutical industries, such as in silico drug target identification and new drug discovery. There are various sequence analysis tools available for mining such useful information of which FASTA and Smith-Waterman algorithms are widely used. However, analyzing large datasets of genome sequences using the above codes seems to be impractical on uniprocessor machines. Hence there is a need for improving the performance of the above popular sequence analysis tools on parallel cluster computers. Performance of the Smith-Waterman (SSEARCH) and FASTA programs were studied on PARAM 10000, a parallel cluster of workstations designed and developed in-house. FASTA and SSEARCH programs, which are available from the University of Virginia, were ported on PARAM and were optimized. In this era of high performance computing, where the paradigm is shifting from conventional supercomputers to the cost-effective general-purpose cluster of workstations and PCs, this study finds extreme relevance. Good performance of sequence analysis tools on a cluster of workstations was demonstrated, which is important for accelerating identification of novel genes and drug targets by screening large databases. Show more

Keywords: comparative genomics, sequence analysis, Smith-Waterman, SSEARCH, FASTA, parallel computing, PARAM 10000, communication networks, fast ethernet, myrinet, PARAMNet, distributed computing, Disperse

Citation: In Silico Biology, vol. 3, no. 4, pp. 429-440, 2003

Authors: Tech, Maike | Merkl, Rainer

Article Type: Research Article

Abstract: The performance of gene-predicting tools varies considerably if evaluated with respect to the parameters sensitivity and specificity or their capability to identify the correct start codon. We were interested to validate tools for gene prediction and to implement a metatool named YACOP, which combines existing tools and has a higher performance. YACOP parses and combines the output of the three gene-predicting systems Criticia, Glimmer and ZCURVE. It outperforms each of the programs tested with its high …sensitivity and specificity values combined with a larger number of correctly predicted gene starts. Performance of YACOP and the gene-finding programs was tested by comparing their output with a carefully selected set of annotated genomes. We found that the problem of identifying genes in prokaryotic genomes by means of computational analysis was solved satisfactorily. In contrast, the correct localization of the start codon still appeared to be a problem, as in all cases under test at least 7.5% and up to 32.3% of the positions given in the annotations differed from the locus predicted by any of the programs tested. YACOP can be downloaded from http://www.g2l.bio.uni-goettingen.de. Show more

Keywords: gene prediction, specificity, sensitivity

Citation: In Silico Biology, vol. 3, no. 4, pp. 441-451, 2003

Authors: Cuperlovic-Culf, Miroslava | Robichaud, Gilles A. | Nardini, Michel | Ouellette, Rodney J.

Article Type: Research Article

Abstract: The Pax-5 transcription factor plays a crucial role in B-cell development, activation and differentiation. In murine B-cells four different isoforms of Pax-5 have been identified, and their role in the regulation of the activity of the wild-type protein was revealed although still not fully understood. Using theoretical methods, we investigated the properties of one region of the Pax-5e and Pax-5d isoforms (named UDE domain) and we present a possible theoretical model for the interaction of this …domain with thioredoxin that have been previously postulated based on the experimental results. Domain UDE (MW 4.8kDa) is characterised by an extremely high ratio of positively charged residues (8) in comparisons to negatively charged amino acids (3), as well as unusually large concentrations of prolines (11.6%) and cysteines (4.7%). This is indicative of its role in protein-protein interaction. The experimental 3D structure for either UDE domain or for any analogous sequence is not yet available, and therefore we resorted to various bioinformatics methods in order to predict the secondary and 3D structure from the primary sequence of UDE. Physicochemical properties of the predicted UDE structure gave more indication about possibilities for UDE-thioredoxin binding. In addition, UDE domain was shown to have both sequence and structure analogous to a segment of NAD-reducing hydrogenase HOXS α subunit which is believed to interact with thioredoxin. These studies showed that the UDE domain in Pax-5d and Pax-5e represents an ideal binding site for thioredoxin and we developed a model of UDE-TRX complex with two disulphide bridges. The active site of thioredoxin remained exposed after binding to UDE in this model and therefore binding of thioredoxin to Pax-5d could explain the unexpectedly high resistance of this isoform to oxidation. The complex between thioredoxin and Pax-5e can be a method for transportation of thioredoxin into the nucleus and also into the the vicinity of Pax-5a, explaining the observed activator role of Pax-5e. Show more

Keywords: protein structure, protein structure prediction, protein-protein interaction, molecular modelling, bioinformatics, transcription factors, alternative splicing, HMMSTR, Rosetta, theoretical analysis, proteomics, electrostatics, disulphide bridge calculation

Citation: In Silico Biology, vol. 3, no. 4, pp. 453-469, 2003

Authors: Gorban, Alexander N. | Zinovyev, Andrei Y. | Popova, Tatyana G.

Article Type: Research Article

Abstract: In several recent papers new gene-detection algorithms were proposed for detecting protein-coding regions without requiring a learning dataset of already known genes. The fact that unsupervised genedetection is possible is closely connected to the existence of a cluster structure in oligomer frequency distributions. In this paper we study the cluster structure of several genomes in the space of their triplet frequencies, using a pure data exploration strategy. Several complete genomic sequences were analyzed, using the …visualization of tables of triplet frequencies in a sliding window. The distribution of 64-dimensional vectors of triplet frequencies displays a well-detectable cluster structure. The structure was found to consist of seven clusters, corresponding to proteincoding information in three possible phases in one of the two complementary strands and in the non-coding regions with high accuracy (higher than 90% on nucleotide level). Visualizing and understanding the structure allows to analyze effectively the performance of different gene-prediction tools. Since the method does not require extraction of ORFs, it can be applied even for unassembled genomes. Show more

Keywords: visualization, gene recognition, unsupervised learning, codon usage

Citation: In Silico Biology, vol. 3, no. 4, pp. 471-482, 2003