In Silico Biology - Volume 5, issue 5-6

Authors: Gaurav, Kumar | Gupta, Nitin | Sowdhamini, Ramanathan

Article Type: Research Article

Abstract: We present an algorithm to detect remote homology, which arises through circular permutation and discontinuous domains. It is also helpful in detecting small domain proteins that are characterized by few conserved residues. The input to the algorithm is a set of multiply aligned protein sequence profiles. This method, coded as FASSM, examines the sequence conservation and positions of protein family signatures or motifs for the annotation of protein sequences and to facilitate the analysis of their …domains. The overall coverage of FASSM is 93% in comparison to other validation tools like HMM and IMPALA. The method is especially useful for difficult relationships such as discontinuous domains during whole-genome surveys and is demonstrated to perform accurate family associations at sequence identities as low as 15%. Availability: Available upon request from the authors. Show more

Keywords: Function annotation, genome databases, protein subfamily, superfamily, function prediction

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 425-438, 2005

Authors: Ju, Zhenlin | Wells, Melissa C. | Martinez, Al | Hazlewood, Leona | Walter, Ronald B.

Article Type: Research Article

Abstract: Teleost fish genome projects involving model species are resulting in a rapid accumulation of genomic and expressed DNA sequences in public databases. The expressed sequence tags (ESTs) collected in the databases can be mined for the analysis of both structural and functional genomics. In this study, we in silico analyzed 49,430 unigenes representing a total of 692,654 ESTs from four model fish for their potential use in developing simple sequence repeats (SSRs), or microsatellites. After bioinformatical …mining, a total of 3,018 EST derived SSRs (EST-SSRs) were identified for 2,335 SSR containing ESTs (SSR-ESTs). The frequency of identified SSR-ESTs ranged from 1.5% for Xiphophorus to 7.3% for zebrafish. The dinucleotide repeat motif is the most abundant SSR, accounting for 47%, 52%, 64%, and 78% for medaka, Fundulus, zebrafish, and Xiphophorus, respectively. Simulation analysis suggests that a majority of these EST-SSRs have sufficient flanking sequences for polymerase chain reaction (PCR) primer design. Comparative DNA sequence analyses of SSR-ESTs identified several cross-species SSRs and sequences that may be used as cross-reference genes in comparative studies. For example, the flanking sequences of one SSR (CTG)n within the pituitary tumor-transforming gene (PTTG) 1 interacting protein (PTTGIP), showed conservation spanning the medaka, Fundulus, human, and mouse genomes. This study provides a large body of information on EST-SSRs that can be useful for the development of polymorphic markers, gene mapping, and comparative genome analysis. Functional analysis of these SSR-ESTs may reveal their role in metabolism and gene evolution of these model species. Show more

Keywords: Model fish, comparative genomics, in silico analysis, PTTGIP, EST, microsatellites, SSR

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 439-463, 2005

Authors: Piva, Francesco | Principato, Giovanni

Article Type: Research Article

Abstract: CORRELATION FINDER is a free software which allows to seek exhaustively correlations between nucleotides in genomic sequences. It permits to analyze generic DNA sequences and genic sequences where the codon phase needs to be taken into account. Its graphic interface allows to easily set the parameters that characterize the motifs being sought. This tool handles large data sets and runs on the Windows operative system. Availability: The software, complete with examples and documentation, is …freely available to users from: http://www.introni.it/en/software. Show more

Keywords: Correlation detection, splicing signal, sequence analysis

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 465-468, 2005

Authors: Prosdocimi, Francisco | Ortega, J. Miguel

Article Type: Research Article

Abstract: When building either DNA or cDNA libraries, a researcher looks at the vector multiple cloning site and chooses which restriction enzyme(s) will be used to clone the inserts. Although this procedure does not seem to be important, the accurate choosing of primer to insert distance can save time and money from genome and transcriptome projects. Here, 846 single-pool pUC18 sequences were produced and compared with the pUC18 consensus using local alignment tools. Data show that reads …often contain 0–20 miscalled bases at the beginning of read and noise to signal transition is frequently found at 46–54 bases from the first 3' base downstream the sequencing primer. For SWAT-based approaches, 60 bases was the distance where over 90% of the sequences provided reliable information, presenting 13 vector bases on average. Looking at the data, it is possible to choose the most appropriate primer to insert distance for many applications. Show more

Keywords: pUC18, cloning vector, Smith-Waterman, BLAST, primer positioning, insert, MegaBACE sequencer

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 469-477, 2005

Authors: Miftahof, Roustem N.

Article Type: Research Article

Abstract: Based on the concept of a functional unit, a mathematical model of a segment of the gut is developed. The model comprises real anatomical, histomorphological, physiological, and pharmacological information on the function of the organ. Numerical investigation into the dynamics of the electromechanical wave phenomenon reveals the fundamental principles of wave initiation, formation, and propagation along electrically anisotropic longitudinal and isotropic circular smooth muscle syncytia. A pattern of self-sustained electrical activity with …the formation of spiral waves is discovered in the longitudinal syncytia and is attributed to the change in conductivity in the syncytia as a result of mechanical deformation of smooth muscle fibers. The model adequately predicts the effects of pharmacological interventions on the dynamics of myoelectrical activity. Although no direct experimental comparison to the theoretical findings is possible at this stage, the proposed mathematical model provides new insight onto the basics of physiological processes – slow wave activity, electromechanical conjugation, etc. – and a clinical entity – gastrointestinal dysrhythmias. Show more

Keywords: Mathematical model, gut, electromechanical wave phenomenon, effects of drugs

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 479-498, 2005

Authors: Ram, Siya | Shanker, Rishi

Article Type: Research Article

Abstract: Diarrheagenic E. coli strains contribute to water related diseases in urban and rural environment in developing and developed world. E. coli pathotype and pathogenicity varies due to complex multifactorial mechanism involving a large number of virulence factors. Rapid assessment of the virulence pattern of E. coli isolates is possible by Real-Time PCR probes like TaqMan. For designing TaqMan probes and primers for multiplex PCR selected E. coli gene sequences: stx1, stx2, hlyA, chuA, eae, lacZ, lamB …and fimA were retrieved from NCBI's GenBank database. The alignment of the multiple sequences and analysis of conserved sequences was carried out using ClustalW and BLAST programs. The primers and Taqmen probes were designed using Beacon Designer software version 2.1 for two multiplexed PCR assays. In silico PCR simulation of these assays showed PCR products for stx2 (248 bp) stx1 (102 bp), lacZ (228bp) and lamB (86 bp) in multiplex #1 and eae (200 bp), chuA (147 bp), hlyA (141bp) and fimA (79 bp) in multiplex #2, respectively. These multiplexed PCR amplification products and probes can be used to identify and confirm presence of O157:H7/H7-, O157:H43/45 and O26:H^{-} /H11 serotypes. In conclusion, multiplex Real-Time Polymerase Chain Reaction oligomers and TaqMan probes designed and validated in silico will be helpful in management of water quality and outbreaks, by improving specificity and minimizing time needed for in vitro verification work. Show more

Keywords: E. coli O157, TaqMan probe, polymerase chain reaction

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 499-504, 2005

Authors: Kaas, Quentin | Lefranc, Marie-Paule

Article Type: Research Article

Abstract: One of the key elements in the adaptive immune response is the presentation of peptides by the major histocompatibility complex (MHC) to the T cell receptors (TR) at the surface of T cells. The characterization of the TR/peptide/MHC trimolecular complexes (TR/pMHC) is crucial to the fields of immunology, vaccination and immunotherapy. In order to facilitate data comparison and cross-referencing between experiments from different laboratories whatever the receptor, the chain type, the domain, or the species, …IMGT, the international ImMunoGeneTics information system® (http://imgt.cines.fr), has developed IMGT-ONTOLOGY, the first ontology in immunogenetics and immunoinformatics. In IMGT/3Dstructure-DB, the IMGT three-dimensional structure database, TR/pMHC molecular characterization and pMHC contact analysis are made according to the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts. IMGT/3Dstructure-DB provides the standardized IMGT gene and allele names (CLASSIFICATION), the standardized IMGT labels (DESCRIPTION) and the IMGT unique numbering (NUMEROTATION). As the IMGT structural unit is the domain, amino acids at conserved positions always have the same number in the IMGT databases, tools and Web resources. For the TR alpha and beta chains, the amino acids in contact with the peptide/MHC (pMHC) are defined according to the IMGT unique numbering for V-DOMAIN. The MHC cleft that binds the peptide is formed by two groove domains (G-DOMAIN), each one comprising four antiparallel beta strands and one alpha helix. The IMGT unique numbering for G-DOMAIN applies both to the first two domains (G-ALPHA1 and G-ALPHA2) of the MHC class I alpha chain, and to the first domain (G-ALPHA and G-BETA) of the two MHC class II chains, alpha and beta. Based on the IMGT unique numbering, we defined eleven contact sites for the analysis of the pMHC contacts. The TR/pMHC contact description, based on the IMGT numbering, can be queried in the IMGT/StucturalQuery tool, at http://imgt.cines.fr. Availability: IMGT/3Dstructure-DB is freely available at http://imgt.cines.fr. Show more

Keywords: IMGT, T cell receptor, TR, major histocompatibility complex, MHC, pMHC, TR/peptide/MHC complex, TR/pMHC, three-dimensional structure, 3D structure, contact analysis, IMGT/3Dstructure-DB, IMGT/StructuralQuery, immunoinformatics, immunogenetics, immune system

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 505-528, 2005

Authors: Takai-Igarashi, Takako

Article Type: Research Article

Abstract: Taking account of the great availability of Petri nets in modeling and analyzing large complicated signaling networks, semantics of Petri nets is in need of systematization for the purpose of consistency and reusability of the models. This paper reports on standardization of units of Petri nets on the basis of an ontology that gives an intrinsic definition to the process of signaling in signaling pathways.

Keywords: Petri net, signaling pathway, ontology, knowledge representation

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 529-536, 2005

Authors: Ulloa, Juan Carlos | Matiz, Adriana | Lareo, Leonardo | Gutiérrez, Maria Fernanda

Article Type: Research Article

Abstract: We are reporting computational studies of several genotyped strains of astrovirus isolated in Colombia which we have genotyped using the 348-bp segment located between nucleotides 258 and 606 close to the amino terminal region of the complete ORF 2. By biocomputational techniques this 348-bp segment from the different strains was translated into an amino acid sequence. The sequences were aligned and compared in order to build a dendrogram. Our results show that the 348 bp and …the 116 amino acid peptides cluster in a very conservative way, showing slight genetic variations between them. This slight sequence variability does not allow us to identify common amino acid substitution patterns shared by all members of each HAstV specific type, thus suggesting that antigenic epitopes are probably located outside the 116 peptide fragment of this capsid protein. These results show that there is little recombination among different regions of the ORF2, thus suggesting that this genotyping method should continue to be useful for serotyping HAstV isolates. Show more

Keywords: Human diarrhea, human astrovirus, ORF 2 of human astrovirus

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 537-546, 2005

Authors: Deyneko, Igor V. | Kel, Alexander E. | Blöcker, Helmut | Kauer, Gerhard

Article Type: Research Article

Abstract: We present an implementation of the signal theory-based approach for detection of novel types of DNA similarity which are based on physical properties of DNA. Systematic study of the sensitivity of the new similarity measure revealed qualitative differences to letter-based similarity. A variety of physical parameters of DNA double strands, which in a straightforward way reflect different kinds of information hidden behind the primary structure of DNA, showed a wide range of recognition power of the …signal similarity measure. We applied the novel DNA similarity measure for the analysis of promoters of E. coli genes. We found that promoter similarities revealed by our approach correlate with their transcription regulatory responsivenesses to different antibiotic and osmotic treatments. Accelerated by special hardware for fast Fourier transformations, the method is easily applicable for the analysis of entire eukaryotic genomes in minutes. Show more

Keywords: Signal theory, pattern recognition, promoter similarities, FeatureScan

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 547-555, 2005

Authors: Mondal, Sukanta | Vijayan, Ramachandran | Shichina, Kannambath | Babu, Rajasekaran Mohan | Ramakumar, Suryanarayanarao

Article Type: Research Article

Abstract: I-superfamily conotoxins have four-disulfide bonds with cysteine arrangement C-C-CC-CC-C-C, and they inhibit or modify ion channels of nerve cells. They have been characterized only recently and are relatively less well studied compared to other superfamily conotoxins. We have detected selective and sensitive sequence pattern for I-superfamily conotoxins. The availability of sequence pattern should be useful in protein family classification and functional annotation. We have built by homology modeling, a theoretical structural 3D …model of ViTx from Conus virgo, a typical member of I-superfamily conotoxins. The modeling was based on the available 3D structure of Janus-atracotoxin-Hv1c of Janus-atracotoxin family whose members have been suggested as possible biopesticides. A study comparing the theoretically modeled structure of ViTx, with experimentally determined structures of other toxins, which share functional similarity with ViTx, reveals the crucial role of C-terminal region of ViTx in blocking therapeutically important voltage-gated potassium channels. Show more

Keywords: I-superfamily conotoxins, protein sequence pattern, homology modeling, shaker K^+ channel, inhibitor cystine knot

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 557-571, 2005

Authors: Hu, ZhiGang | Chen, KePing | Wang, LinLing | Yao, Qin

Article Type: Research Article

Abstract: As the genome of B. mori is available in GenBank and the EST database of B. mori is expanding, identification of novel genes of B. mori was conceivable by data-mining techniques and bioinformatics tools. In this study, we used the in silico cloning method to identify eukaryotic initiation factor 5A (eIF5A) gene in B. mori. With the hypusine formation, eIF5A is involved in the regulation of cell proliferation and apoptosis. Using the computer program MEGA3, we …conducted a search for homologs of eIF5A among many eukaryotic species and confirmed that the eIF5A was conserved in all organisms investigated. This gene has been registered in GenBank under the accession number DQ104412. Show more

Keywords: eIF5A, Bombyx mori, EST, in silico cloning

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 573-580, 2005

Authors: Cortez, Diego Q. | Lazcano, Antonio | Becerra, Arturo

Article Type: Research Article

Abstract: With the advent of larger genome databases detection of horizontal gene transfer events has been transformed into an increasingly important issue. Here we present a simple theoretical analysis based on the in silico artificial addition of known foreign genes from different prokaryotic groups into the genome of Escherichia coli K12 MG1655. Using this dataset as a control, we have tested the efficiency of four methodologies commonly employed to detect HTG (Horizontally transferred genes), which are based …on (a) the codon adaptation index, codon usage, and GC percentage (CAI/GC); (b) a distributional profile (DP) approach made by a gene search in the closely related phylogenetic genomes; (c) a Bayesian model (BM); and (d) a first-order Markov model (MM). All methods exhibit limitations although, as shown here, the BM and the MM are better approximations. Moreover, the MM has demonstrated a more accurate rate of detections when genes from closely related organisms are evaluated. The application of the MM to detect recently transferred genes in the genomes of E. coli strains K12 MG1655, O157 EDL933, and Salmonella typhimurium, shows that these organisms have undergone a rather significant amount of HTG, most of which appear to be pseudogenes. Few of these sequences that have undergone HGT appear to have well defined functions and may be involved in the organism's adaptation. Show more

Keywords: Horizontally transferred gene, methodologies to detect HTG, first-order Markov model

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 581-592, 2005

Authors: Ankra-Badu, Georgina A. | Aggrey, Samuel E.

Article Type: Research Article

Abstract: This study was undertaken to identify novel candidate genes at quantitative trait loci (QTL) on chicken chromosome Z (GGAZ) by comparing orthologous regions of chicken, human and mouse genomes. Primer sequences from marker flanking QTL positions (https://acedb.asg.wur.nl/) were obtained from www.iastate.edu/chickmap and blasted against the chicken genome (www.ensembl.org) using BLASTN. The best matches were those with the highest score, lowest E-values and highest percent identity. Orthologous regions in mice and humans, together …with genes located on or around those loci were identified using the Ensembl website. Forty-six chicken genes, 91 mouse genes and 60 human genes associated with QTL on GGAZ were identified in the current study. Among the most promising candidate genes for egg production and egg shell quality are annexin A1 (ANXA1), osteoclast stimulating factor (OSF), thrombospondin-4 (THBS4), programmed cell death proteins (PDCD), follistatin (FST), growth hormone receptor (GHR), interferon (IFN) α and β. The chicken IFN α and β were located on GGAZ around position 13,000,000 bp on the draft chicken sequence map. The neuronal nicotinic acetylcholine receptor (nAChR) is located at a QTL region for abdominal fat (GGAZ 25483091 bp). Nicotine is an agonist at the nAChRs and has been shown to decrease lipolysis and triglyceride uptake, thereby reducing net storage in adipose tissue. Therefore, the nAchRs could be used as therapeutic targets for regulating feed intake and obesity. This study has identified 197 putative candidate genes in probable QTL regions of chicken chromosome Z. Show more

Keywords: Candidate genes, quantitative trait loci, chicken chromosome Z, comparative mapping

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 593-604, 2005

Authors: Babu, P. Ajay | Boddepalli, Radha | Lakshmi, V. Vasantha | Rao, G. Nageswara

Article Type: Research Article

Abstract: Database of Databases (DoD) is a collection of molecular biology databases extracted from Nucleic Acids Research, 2005 Database issue. DoD is constructed using javascript and html code. The 14 categories of 719 databases are provided with a search option, keyword help and database description linked to respective pages. Keyword help lists the search strings used to perform an individual search against categorized databases. Database description provides brief information about the database with a link to full-text …article and main web page. DoD is available online and can be accessed at http://www.progenebio.in/DoD/DoD.htm. Show more

Keywords: Molecular biology databases, nucleotide sequence databases, RNA sequence databases, protein sequence databases, structure databases, genomics databases, metabolic & signaling pathways, human and vertebrate genomes, human genes and diseases, microarray data and gene expression databases, proteomics resources, organelle databases, plant databases, immunological databases

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 605-610, 2005

Authors: Sakharkar, Kishore Ramaji | Chaturvedi, Iti | Chow, Vincent T.K. | Kwoh, Chee Keong | Kangueane, Pandjassarame | Sakharkar, Meena Kishore

Article Type: Research Article

Abstract: Unicellular eukaryotes were among the first ones to be selected for complete genome sequencing because of the small size of their genomes and their interactions with humans and a broad range of animals and plants. Currently, ten completely sequenced unicellular genome sequences have been publicly released and as the number of available unicellular genomes increases, comparative genomics analysis within this group of organisms becomes more and more instructive. However, such an analysis is difficult to carry …out without a suitable platform gathering not only the original annotations but also relevant information available in public databases or obtained by applying common bioinformatics methods. With the aim of solving these difficulties, we have developed a web-accessible database named u-Genome, the unicellular genome design database. The database is unique in featuring three datasets namely (1) orthologous proteins (2) paralogous proteins and (3) statistical distributions on exons, introns, intergenic DNA and correlations between them. A tool, Uniview, designed to visualize the gene structures for individual genes in the genome is also integrated. This database is of importance in understanding unicellular genome design and architecture and evolution related studies. The database is available through a web interface at http://sege.ntu.edu.sg/wester/ugenome. Show more

Keywords: Unicellular genomes, design, architecture, exon-intron lengths, paralogs, orthologs

Citation: In Silico Biology, vol. 5, no. 5-6, pp. 611-615, 2005