In Silico Biology - Volume 5, issue 4

Authors: Sakharkar, Meena Kishore | Perumal, Bagavathi S. | Sakharkar, Kishore R. | Kangueane, Pandjassarame

Article Type: Research Article

Abstract: A comparative genome analysis on exon-intron distribution profiles is performed for human and mouse genomes to deduce similarities and differences between them. Interestingly, both in human and mouse genomes, the total length in introns and intergenic DNA on each chromosome is significantly correlated to the chromosome size. The results presented provide a framework for understanding the nature and patterns of exon-intron length distributions, the constraints on them and their role in genome design and evolution.

Keywords: Exon, intron, length, shape, genome architecture, genome design, human, mouse, comparative genomics, distribution, profiles, correlation, genome size, architectural constraints, chromosome, gene density, content

Citation: In Silico Biology, vol. 5, no. 4, pp. 347-365, 2005

Authors: Enerly, Espen | Sheng, Zeng | Li, Kuo-Bin

Article Type: Research Article

Abstract: In humans an estimated 35–60% of genes are alternatively spliced. A large number of genes also show alternative initiation or termination. Regulation of these processes is still poorly understood. For alternative splicing it is believed that the relative concentration of certain proteins and the presence of certain regulatory elements are the key factors determining alterations in splicing pattern. However, there is evidence that antisense RNA might be part of the regulatory processes. Antisense RNA molecules could …bind to the target pre-mRNA in a sequence-specific fashion, sterically blocking targeted splice sites and redirecting the spliceosome to available and unhindered splice sites. Here we describe an in silico investigation to identify human sense/antisense pairs with alternative initiation or termination in the sense gene and where only one of the isoforms overlaps the antisense transcript. Alternatively spliced genes with antisense transcripts covering the alternatively used splice site are also identified. Our analyses are based on the ASAP splicing annotation database from UCLA, the antisense transcripts data from Yelin et al., 2003, and the H-invitational full-length cDNA database from JBIRC, Japan. These data gives new insight into the complexity of genomic organization and provide candidate loci for experimentalists to study antisense mediated regulation of alternative initiation, splicing and termination. Our result contains 468 clusters with this characteristic genomic organization and can be found at http://aistar.bii.a-star.edu.sg/. Show more

Keywords: Antisense, alternative splicing, alternative initiation, alternative termination, gene regulation, non-coding RNA

Citation: In Silico Biology, vol. 5, no. 4, pp. 367-377, 2005

Authors: Bhadra, Rana | Srinivasan, Narayanaswamy | Pandit, Shashi B.

Article Type: Research Article

Abstract: During the course of our large-scale genome analysis a conserved domain, currently detectable only in the genomes of Drosophila melanogaster, Caenorhabditis elegans and Anopheles gambiae, has been identified. The function of this domain is currently unknown and no function annotation is provided for this domain in the publicly available genomic, protein family and sequence databases. The search for the homologues of this domain in the non-redundant sequence database using PSI-BLAST, resulted …in identification of distant relationship between this family and the alkaline phosphatase-like superfamily, which includes families of aryl sulfatase, N-acetylgalactosomine-4-sulfatase, alkaline phosphatase and 2,3-bisphosphoglycerate-independent phosphoglycerate mutase (iPGM). The fold recognition procedures showed that this new domain could adopt a similar 3-D fold as for this supefamily. Most of the phosphatases and sulfatases of this superfamily are characterized by functional residues Ser and Cys respectively in the topologically equivalent positions. This functionally important site aligns with Ser/Thr in the members of the new family. Additionally, set of residues responsible for a metal binding site in phosphatases and sulphtases are conserved in the new family. The in-depth analysis suggests that the new family could possess phosphatase activity. Show more

Keywords: Functional domains, phosphatases, protein domains, sequence analysis, sulfatases

Citation: In Silico Biology, vol. 5, no. 4, pp. 379-387, 2005

Authors: Johnson, Robin J. | Williams, Jennifer M. | Schreiber, Barbara M. | Elfe, Charles D. | Lennon-Hopkins, Kelley L. | Skrzypek, Marek S. | White, Renee D.

Article Type: Research Article

Abstract: Microarray technology has resulted in an explosion of complex, valuable data. Integrating data analysis tools with a comprehensive underlying database would allow efficient identification of common properties among differentially regulated genes. In this study we sought to compare the utility of various databases in microarray analysis. The Proteome BioKnowledge® Library (BKL), a manually curated, proteome-wide compilation of the scientific literature, was used to generate a list of Gene Ontology (GO) Biological Process …(BP) terms enriched among proteins involved in cardiovascular disease. Analysis of DNA microarray data generated in a study of rat vascular smooth muscle cell responses revealed significant enrichment in a number of GO BPs that were also enriched among cardiovascular disease-related proteins. Using annotation from LocusLink and chip annotation from the Gene Expression Omnibus yielded fewer enriched cardiovascular disease-associated GO BP terms. Data sets of orthologous genes from mouse and human were generated using the BKL Retriever. Analysis of these sets focusing on BKL Disease annotation, revealed a significant association of these genes with cardiovascular disease. These results and the extensive presence of experimental evidence for BKL GO and Disease features, underscore the benefits of using this database for microarray analysis. Show more

Keywords: Microarray analysis, gene ontology, disease, cardiovascular disease, protein databases

Citation: In Silico Biology, vol. 5, no. 4, pp. 389-399, 2005

Authors: Prasad, Pandurangan Arun | Vengadesan, Krishnan | Gautham, Namasivayam

Article Type: Research Article

Abstract: We describe a computer program that uses mutually orthogonal Latin squares (MOLS) to perform an efficient and exhaustive conformational search of the multi-dimensional potential energy hypersurface of an oligopeptide, and locate all its low energy conformations. The software package has been developed with a user-friendly graphical interface using the Fast Light Tool Kit (FLTK) – a cross platform C++ toolkit.

Keywords: Peptide structure prediction, mutually orthogonal Latin squares (MOLS), low energy conformations, potential energy hypersurface

Citation: In Silico Biology, vol. 5, no. 4, pp. 401-405, 2005

Authors: Jeffries, Clark | Jarstfer, Michael | Perkins, Diana O.

Article Type: Research Article

Abstract: Homeostatic maintenance of mRNA levels including prompt availability of mRNAs for translation in response to changing protein demands might be partly enabled by a system of combinatorial controls involving noncoding RNA blocking agents. This article proposes a specific version of that control mechanism, namely, a double-stranded RNA folding from transcription of an intron of one gene might and leading to an agent that inhibits mRNA of a counteracting gene. Thus transcription of the first gene would …automatically repress translation of the second. On the basis of a bioinformatics search, we suggest a possible example, namely, that pro-apoptosis gene PAR4 might inhibit anti-apoptosis gene XIAP. Part of an intron from PAR4 folds to form a large, stable hairpin, and reverse complement of the hairpin stem (with ∼280 nucleotides) matches a sub-sequence of an exon in XIAP. This would be part of an efficient system to drive initiated apoptosis to its conclusion. Figuratively speaking, it replaces two control knobs with one. Since repeats, some with many thousands of copies, occur throughout the genome with complex distributions, care must be taken before asserting that the presence of any repeat in any gene is significant. Our apoptosis example involves repeats, so experimental verification is needed and planned. However, if it is found that the noncoding RNA by-product of one gene folds into a hairpin that is processed into an agent that inhibits a counteracting gene, then the same type of control unit might be found extensively among counteracting families of genes of many types. Show more

Keywords: Counteracting genes, RNA hairpins, noncoding RNA, miRNA, Alu repeat

Citation: In Silico Biology, vol. 5, no. 4, pp. 407-413, 2005

Authors: Riaz, Tariq | Li, Kuo-Bin | Tang, Francis | Krishnan, Arun

Article Type: Research Article

Abstract: CMDWave (Conserved Motif Detection using WAVElets) is a web server that predicts conserved motifs in protein sequences. A set of query protein sequences are first aligned using ClustalW to obtain equal sized sequences. CMDWave then converts the sequences into a numerical representation using electron-ion interaction potential (EIIP). This is followed by a wavelet decomposition and reconstruction. A new similarity metric along with thresholding is then used to identify conserved motifs across all the query …sequences. Users need not specify the number of motifs to be identified. For larger groups of sequences, results can be emailed to the users. Show more

Keywords: Motif detection, physicochemical properties, wavelet analysis

Citation: In Silico Biology, vol. 5, no. 4, pp. 415-418, 2005

Authors: Arakawa, Kazuharu | Kono, Nobuaki | Yamada, Yohei | Mori, Hirotada | Tomita, Masaru

Article Type: Research Article

Abstract: Pathway-level visualization of omics data provides an essential means for systems biology, to capture the systematic properties of the inner activities of cells. Here we describe a web-based resource consisting of a web-application for the visualization of complex omics data onto KEGG pathways to overview all entities in the context of cellular pathways, and databases created with the software to visualize a series of microarray data. The web-application accepts transcriptome, proteome, metabolome, or the combination …of these data as input, and because of this scalability it is advantageous for the visualization of cell simulation results. The web server can be accessed at http://www.g-language.org/data/marray/. Show more

Keywords: KEGG, pathway visualization, systems biology, microarray, transcriptome, metabolome

Citation: In Silico Biology, vol. 5, no. 4, pp. 419-423, 2005