In Silico Biology - Volume 7, issue 4-5

Authors: Wen, Jiayu | Parker, Brian J. | Weiller, Georg F.

Article Type: Research Article

Abstract: Accumulating evidence suggests that that non-coding RNAs (ncRNAs) play key roles in gene regulation and may form the basis of an inter-gene communication system. Many ncRNAs are synthesized similar to mRNAs and can be detected through screening of polyA-rich EST or cDNA libraries. We developed a computational pipeline to screen EST and genomic sequence data for those transcribed genes with limited protein coding potential and applied this pipeline to the model legume Medicago truncatula. This process …identified a set of 503 mRNA-like transcripts that appear not to encode proteins. Further computational analysis showed that many of these ncRNA candidates share structural similarities to known ncRNAs and that they clearly differ from protein coding genes and non-transcribed regions in their base and oligonucleotide compositions, as well as in aspects of secondary structure. By using a machine learning approach, we show that the distinctive ncRNA features presented in this study can be used to discriminate most ncRNAs and may thus be useful for improving ncRNA prediction. Computational analysis of EST isolation frequencies in various plant tissues showed that the expression levels and expression profiles of the putative ncRNAs and mRNAs differ – most interestingly, the putative ncRNAs are highly expressed relative to mRNAs in the root nodule tissue and conserved only in closely related plants. The work presented here constitutes the first large-scale prediction and characterization of ncRNAs in legumes, and provides a basis for further research on elucidating ncRNA function in legume genomics. Show more

Keywords: ncRNA, mRNA-like ncRNA, EST, Medicago truncatula, model legume, SVM, feature classification

Citation: In Silico Biology, vol. 7, no. 4-5, pp. 485-505, 2007

Authors: Ramazzotti, Matteo | Brilli, Matteo | Fani, Renato | Manao, Giampaolo | Degl'Innocenti, Donatella

Article Type: Research Article

Abstract: The Codon Adaptation Index (CAI) was introduced by Sharp and Li in 1987 to quantify codon usage similarities between a coding sequence and a set of reference sequences. When synonymous codons for a given amino acid exist, highly expressed genes seem to prefer some of them, according to tRNA abundance and thermodynamic issues. Some authors have described CAI-based methods to derive expressivity measures for all genes in a genome, in a computational framework. Here …we present the CAIAP (CAI Analyser Package), a platform independent package of computer programs allowing the calculation of the CAI and a deep study of gene expressivity from raw gene sequences. Our approach implements and optimizes a procedure to derive the reference sequences from whole genomes and use their codon usage for CAI estimation. Moreover, a set of analysis tools are provided to perform statistical analyses and therefore to give robustness to results. Objective: Our efforts were aimed to produce an easy-to-use and fully automatic set of programs specifically designed for the analysis of gene expressivity and inter-species comparisons on a great number of genomes. Moreover, the output integrates information coming from functional annotations of genes. We are maintaining a web server storing our analyses for hundreds of genomes, allowing intergenomic comparison of data thanks to dedicated search engines. The CAIAP server is hosted at www4.unifi.it/scibio/bioinfo/caiap/html. The programs (maintained as Perl scripts) are also available for download at the same location. Show more

Keywords: Gene expressivity, Codon Adaptation Index, intergenomic comparison, program package, web server

Citation: In Silico Biology, vol. 7, no. 4-5, pp. 507-526, 2007

Authors: Liao, Li | Li, Zhongwei

Article Type: Research Article

Abstract: Antisense oligonucleotides inactivate mRNA targets, providing a tool for post-transcriptional gene silencing and a potential novel treatment for many diseases. Reliable design of active antisense depends on better understanding of the mechanism of antisense-target RNA interaction. We have studied the correlation between activity of antisense oligodeoxynucleotides (ASO) and structural features of both antisense and target RNAs. A total of 348 ASOs with known activities and their target RNA sequences are classified into …categories according to their predicted secondary structural features. Statistical analysis showed that higher activity is more likely to happen at RNA stem-loops than at other RNA structural categories. The data suggest a weak correlation between the stability of ASO structure and activity. Remarkably, a structural fit between ASO and target seems important for antisense activity. Significantly higher antisense activity is achieved with stem-loop ASOs on stem-loop or linear RNA targets. Show more

Keywords: Antisense, RNA, gene inactivation, mRNA target, secondary structure, oligodeoxynucleotides, stem-loop, statistical analysis

Citation: In Silico Biology, vol. 7, no. 4-5, pp. 527-534, 2007

Authors: Zimmermann, Olav | Wang, Longhui | Hansmann, Ulrich H.E.

Article Type: Research Article

Abstract: Most secondary structure prediction programs do not distinguish between parallel and antiparallel β-sheets. However, such knowledge would constrain the available topologies of a protein significantly, and therefore aid existing fold recognition algorithms. For this reason, we propose a technique which, in combination with existing secondary structure programs such as PSIPRED, allows one to distinguish between parallel and antiparallel β-sheets. We propose the use of a support vector machine (SVM) procedure, BETTY, to …predict parallel and antiparallel sheets from sequence. We found that there is a strong signal difference in the sequence profiles which SVMs can efficiently extract. With strand type assignment accuracies of 90.7% and 83.3% for antiparallel and parallel strands, respectively, our method adds considerably to existing information on current 3-class secondary structure predictions. BETTY has been implemented as an online service which academic researchers can access from our website http://www.fz-juelich.de/nic/cbb/service/service.php. Show more

Keywords: SVM, support vector machine, structure prediction, secondary structure prediction, tertiary structure prediction, beta-sheets, beta-strands, parallel beta-sheets, antiparallel beta-sheets, long range constraints

Citation: In Silico Biology, vol. 7, no. 4-5, pp. 535-542, 2007

Authors: Marla, Soma | Singh, Vinay Kumar

Article Type: Research Article

Abstract: Recent sequencing of genomes of several microorganisms provides an opportunity to have access to huge volumes of data stored in various databases. This has resulted in the development of various computational and visualization tools to aid in retrieval and analysis of data. Development of user friendly genome data mapping and visualization tools facilitates researchers to closely examine various features of genes and make inferences from the displayed data efficiently. PGV – Prokaryotic Genome Viewer is a …Java based web application tool capable of generating high quality interactive circular chromosome maps. With simple mouse roll over tasks on the interested region on the displayed map, the user is provided with features such as feature labeling, multi-fold zooming, image rotation and hyperlinking to different information resources. The tool is capable of instantaneously generating maps using user-supplied sequence data. Show more

Keywords: Prokaryotes, visualization, genomic maps, Java, zooming, display tool

Citation: In Silico Biology, vol. 7, no. 4-5, pp. 543-545, 2007

Authors: Sen, Gargi | Sur, Saubashya | Bose, Debadin | Mondal, Uttam | Furnholm, Teal | Bothra, Asim | Tisa, Louis | Sen, Arnab

Article Type: Research Article

Abstract: Members of the genus Xanthomonas are significant phytopathogens, which cause diseases in several economically important crops including rice, canola, tomato, citrus, etc. We have analyzed the genomes of six recently sequenced Xanthomonas strains for their synonymous codon usage patterns for all of protein coding genes and specific genes associated with pathogenesis, and determined the predicted highly expressed (PHX) genes by the use of the codon adaptation index (CAI). Our results show considerable …heterogeneity among the genes of these moderately G+C rich genomes. Most of the genes were moderate to highly biased in their codon usage. However, unlike ribosomal protein genes, which were governed by translational selection, those genes associated with pathogenesis (GAP) were affected by mutational pressure and were predicted to have moderate to low expression levels. Only two out of 339 GAP genes were in the PHX category. PHX genes present in clusters of orthologous groups of proteins (COGs) were identified. Genes in the plasmids present in two strains showed moderate to low expression level and only a couple of genes featured in the PHX list. Common genes present in the top-20 PHX gene-list were identified and their possible functions are discussed. Correspondence analysis showed that genes are highly confined to a core in the plot. Show more

Keywords: Codon usage, codon adaptation index, correspondence analysis, pathogenicity, Xanthomonas

Citation: In Silico Biology, vol. 7, no. 4-5, pp. 547-558, 2007