In Silico Biology - Volume 5, issue 3

Authors: Sakharkar, Meena Kishore | Perumal, Bagavathi S. | Lim, Yun Ping | Chern, Lee Pern | Yu, Yiting | Kangueane, Pandjassarame

Article Type: Research Article

Abstract: Alternative splicing of mRNA allows many gene products with different functions to be produced from a single coding sequence. Exon skipping is the most commonly known alternative splicing mechanism. A comprehensive database of alternative splicing by exon skipping is made available for the human genome data. 1,229 human genes are identified to exhibit alternative splicing by exon skipping.

Keywords: alternative splicing, eukaryotic gene structure, exon skipping, multiple splice variants, protein isoforms, protein diversity, skipping patterns, genome wide splicing, full length cDNA sequences, tissue specificity, computational analysis, database

Citation: In Silico Biology, vol. 5, no. 3, pp. 221-225, 2005

Authors: Brylinski, Michal | Konieczny, Leszek | Roterman, Irena

Article Type: Research Article

Abstract: Estimation of structure predictability for a particular protein is difficult. Many methods estimate it in an a posteriori system evaluating the final, native protein structure. The SPI scale is intended to estimate the structure predictability of a {particular} amino acid sequence in an a priori system. A sequence-to-structure library was created based on the complete Protein Data Bank. The tetrapeptide was selected as a unit representing a well-defined structural motif. The early-stage folding structure (a model …of which was presented elsewhere) was taken as the object for protein structure classification. Seven structural forms were distinguished for structure classification. The degree of determinability was estimated for the sequence-to-structure and structure-to-sequence relations particularly interesting for threading methods. A comparative analysis of the SPI and Q7 scales with the commonly used SOV and Q3 scales is presented. The complete contingency table, supplementary materials and all the programs used are available on request. Show more

Keywords: protein structure prediction, predictability scale, early-stage of folding

Citation: In Silico Biology, vol. 5, no. 3, pp. 227-237, 2005

Authors: Lindlöf, Angelica | Lubovac, Zelmina

Article Type: Research Article

Abstract: Recent research on large scale microarray analysis has explored the use of Relevance Networks to find networks of genes that are associated to each other in gene expression data. In this work, we compare Relevance Networks with other types of clustering methods to test some of the stated advantages of this method. The dataset we used consists of artificial time series of Boolean gene expression values, with the aim of mimicking microarray data, generated from simple …artificial genetic networks. By using this dataset, we could not confirm that Relevance Networks based on mutual information perform better than Relevance Networks based on Pearson correlation, partitional clustering or hierarchical clustering, since the results from all methods were very similar. However, all three methods successfully revealed the subsets of co-expressed genes, which is a valuable step in identifying co-regulation. Show more

Keywords: relevance Networks, clustering, regulatory networks, microarray data analysis, simulation

Citation: In Silico Biology, vol. 5, no. 3, pp. 239-249, 2005

Authors: Peng, Jianbin | Huang, Cheng-Han | Short, Mary K. | Jubinsky, Paul T.

Article Type: Research Article

Abstract: Magmas is a nuclear encoded protein found in the mitochondria of mammalian cells. It participates in granulocyte-macrophage-colony stimulating factor (GM-CSF) signaling in hematopoietic cells and has an essential role in invertebrate development. In order to characterize the protein structural features and gene evolution of Magmas, a dataset containing 61 Magmas homologs from 52 species distributed among animals, plants and fungi was analyzed. All Magmas members were found to possess three novel sequence motifs in addition to …a conserved leader peptide. Phylogenetic tree and dN/dS rate ratios showed that Magmas was evolutionarily conserved. Analysis of Magmas gene organization demonstrated incremental intron acquisition in plants and vertebrates. Significant genetic diversity in Magmas was observed from kingdom specific amino acid signatures, the presence of predicted signal peptides that target the protein to other intracellular locations besides the mitochondria, and the detection of multiple isoforms in higher animals. These studies demonstrate that Magmas members constitute an important family of conserved proteins having multifunctional activities, and provide a basis for future experiments. Show more

Keywords: mitochondria, GM-CSF, alternative splicing, gene duplication, functional divergence

Citation: In Silico Biology, vol. 5, no. 3, pp. 251-263, 2005

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

Article Type: Research Article

Abstract: Coding information is the main source of heterogeneity (non-randomness) in the sequences of microbial genomes. The heterogeneity corresponds to a cluster structure in triplet distributions of relatively short genomic fragments (200–400 bp). We found a universal 7-cluster structure in microbial genomic sequences and explained its properties. We show that codon usage of bacterial genomes is a multi-linear function of their genomic G+C-content with high accuracy. Based on the analysis of 143 completely …sequenced bacterial genomes available in Genbank in August 2004, we show that there are four "pure" types of the 7-cluster structure observed. All 143 cluster animated 3D-scatters are collected in a database which is made available on our web-site (http://www.ihes.fr/~zinovyev/7clusters). The findings can be readily introduced into software for gene prediction, sequence alignment or microbial genomes classification. Show more

Keywords: word frequency, codon usage, clustering, visualization, symmetry

Citation: In Silico Biology, vol. 5, no. 3, pp. 265-282, 2005

Authors: de Brevern, Alexandre G.

Article Type: Research Article

Abstract: A statistical analysis of the Protein Databank (PDB) structures had led us to define a set of small 3D structural prototypes called Protein Blocks (PBs). This structural alphabet includes 16 PBs, each one defined by the (ϕ, ψ) dihedral angles of 5 consecutive residues. Here, we analyze the effect of the enlargement of the PDB on the PBs' definition. The results highlight the quality of the 3D approximation ensured by the PBs. These last could be …of great interest in ab initio modeling. Show more

Keywords: secondary structure, structure-sequence relationship, ab initio modeling

Citation: In Silico Biology, vol. 5, no. 3, pp. 283-289, 2005

Authors: Wolf, Matthias | Friedrich, Joachim | Dandekar, Thomas | Müller, Tobias

Article Type: Research Article

Abstract: The CBCAnalyzer (CBC = compensatory base change) is a custom written software toolbox consisting of three parts, CTTransform, CBCDetect, and CBCTree. CTTransform reads several ct-file formats, and generates a so called "bracket-dot-bracket" format that typically is used as input for other tools such as RNAforester, RNAmovie or MARNA. The latter one creates a multiple alignment based on primary sequences and secondary structures that now can be used as input for CBCDetect. CBCDetect counts CBCs in all …against all of the aligned sequences. This is important in detecting species that are discriminated by their sexual incompatibility. The count (distance) matrix obtained by CBCDetect is used as input for CBCTree that reconstructs a phylogram by using the algorithm of BIONJ. In this note we describe the features of the toolbox as well as application examples. The toolbox provides a graphical user interface. It is written in C++ and freely available at: http://cbcanalyzer.bioapps.biozentrum.uni-wuerzburg.de. Show more

Keywords: compensatory base change (CBC), internal transcribed spacer 2 (ITS2), phylogeny, rRNA, secondary structure

Citation: In Silico Biology, vol. 5, no. 3, pp. 291-294, 2005

Authors: Möller, Steffen | Mix, Eilhard | Blüggel, Martin | Serrano-Fernández, Pablo | Koczan, Dirk | Kotsikoris, Vasilis | Kunz, Manfred | Watson, Michael | Pahnke, Jens | Illges, Harald | Kreutzer, Michael | Mikkat, Stefan | Thiesen, Hans-Jürgen | Glocker, Michael O. | Zettl, Uwe K. | Ibrahim, Saleh M.

Article Type: Research Article

Abstract: The existence of a soluble splice variant for a gene encoding a transmembrane protein suggests that this gene plays a role in intercellular signalling, particularly in immunological processes. Also, the absence of a splice variant of a reported soluble variant suggests exclusive control of the solubilisation by proteolytic cleavage. Soluble splice variants of membrane proteins may also be interesting targets for crystallisation as their structure may be expected to preserve, at least partially, their function as …integral membrane proteins, whose structures are most difficult to determine. This paper presents a dataset derived from the literature in an attempt to collect all reported soluble variants of membrane proteins, be they splice variants or shedded. A list of soluble variants is derived in silico from Ensembl. These are checked on their presence in multiple organisms and their number of membranespanning regions is inspected. The findings then are confirmed by a comparison with identified proteins of a recent global proteomics study of human blood plasma. Finally, a tool to support the identification of novel soluble variants by proteomics is provided. Show more

Keywords: soluble membrane proteins, splice variants, mass spectrometry, proteolytic cleavage, ectodomain shedding, human, mouse, rat, immune response

Citation: In Silico Biology, vol. 5, no. 3, pp. 295-311, 2005

Authors: Berman, Jules J.

Article Type: Research Article

Abstract: Assigning nomenclature codes to biomedical data is an arduous, expensive and error-prone task. Data records are coded to to provide a common representation of contained concepts, allowing facile retrieval of records via a standard terminology. In the medical field, cancer registrars, nurses, pathologists, and private clinicians all understand the importance of annotating medical records with vocabularies that codify the names of diseases, procedures, billing categories, etc. Molecular biologists need codified medical records …so that they can discover or validate relationships between experimental data and clinical data. This paper introduces a new approach to retrieving data records without prior coding. The approach achieves the same result as a search over pre-coded records. It retrieves all records that contain any terms that are synonymous with a user's query-term. A recently described fast algorithm (the doublet method) permits quick iterative searches over every synonym for any term from any nomenclature occurring in a dataset of any size. As a demonstration, a 105+ Megabyte corpus of Pubmed abstracts was searched for medical terms. Query terms were matched against either of two vocabularies and expanded as an array of equivalent search items. A single search term may have over one hundred nomenclature synonyms, all of which were searched against the full database. Iterative searches of a list of concept-equivalent terms involves many more operations than a single search over pre-annotated concept codes. Nonetheless, the doublet method achieved fast query response times (0.05 seconds using Snomed and 5 seconds using the Developmental Lineage Classification of Neoplasms, on a computer with a 2.89 GHz processor). Pre-annotated datasets lose their value when the chosen vocabulary is replaced by a different vocabulary or by a different version of the same vocabulary. The doublet method can employ any version of any vocabulary with no pre-annotation. In many instances, the enormous effort and expense associated with data annotation can be eliminated by on-the-fly doublet matching. The algorithm for nomenclature-based database searches using the doublet method is described. Perl scripts for implementing the algorithm and testing execution speed are provided as open source documents available from the Association for Pathology Informatics (www.pathologyinformatics.org/informatics_r.htm). Show more

Keywords: nomenclature, taxonomy, classification, autocoding, indexing, annotation, metadata, algorithm, data integration, Perl, doublet method, doublet matching

Citation: In Silico Biology, vol. 5, no. 3, pp. 313-322, 2005

Authors: Dormer, Anton | Beck, Gregory

Article Type: Research Article

Abstract: Human vascular endothelial growth factor (VEGF), angiopoietin (ANG) and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE)-2 consist of a grouping of proteins that are involved in vascular homeostasis, vascular integrity and angiogenesis. There are nine proteins in the immediate VEGF family: VEGFA, VEGFB, VEGFC, VEGFD, VEGF-3, placental growth factor (PGF), VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-1-related. They can be stimulated by cytokines to become involved in immune responses. By using …in silico tools, we were able to identify several possible analogues or homologues of VEGF, ANG and TIE-2 in invertebrates. This is the first report to show that these proteins may be conserved through evolution. These proteins may have a role in vascular maintenance and immunity. In addition, since VEGF, ANG and TIE-2 have a role in mammalian immunity that is significantly influenced by cytokines, such as IL-1, this may indicate an interaction of the vascular system and the immune system over evolutionary time. Show more

Keywords: immunology, angiogenesis, evolution, cytokine, protein sequence, human vascular endothelial growth factor, angiopoietin, tyrosine endothelial kinase, vascular homeostasis, vascular integrity, invertebrate, endothelial growth factor

Citation: In Silico Biology, vol. 5, no. 3, pp. 323-339, 2005