Comparative Analysis of Cyclic Sequences: Viroids and other Small Circular RNA`s

The analysis of small circular sequences requires specialized tools. While the differences between linear and circular sequences can be neglected in the case of long molecules such as bacterial genomes since in practice all analysis is performed in sequence windows, this is not true for viroids and related sequences which are usually only a few hundred basepairs long. In this contribution we present basic algorithms and corresponding software for circular RNAs. In particular, we discuss the problem of pairwise and multiple cyclic sequence alignments with affine gap costs, and an extension of a recent approach to circular RNA folding to the computation of consensus structures

Computational analysis of expressed sequence tags for understanding gene regulation.

High-throughput sequencing has provided a myriad of genetic data for thousands of organisms. Computational analysis of one data type, expressed sequence tags (ESTs) yields insight into gene expression, alternative splicing, tissue specificity gene functionality and the detection and differentiation of pseudogenes. Two computational methods have been developed to analyze alternative splicing events and to detect and characterize pseudogenes using ESTs. A case study of rat phosphodiesterase 4 (PDE4) genes yielded more than twenty-five previously unreported isoforms. These were experimentally verified through wet lab collaboration and found to be tissue specific. In addition, thirteen cytochrome-like gene and pseudogene sequences from the human genome were analyzed for pseudogene properties. Of the thirteen sequences, one was identified as the actual cytochrome gene, two were found to be non-cytochrome-related sequences, and eight were determined to be pseudogenes. The remaining two sequences were identified to be duplicates. As a precursor to applying the two new methods, the efficiency of three BLAST algorithms (NCBI BLAST, WU BLAST and mpiBLAST) were examined for comparing large numbers of short sequences (ESTs) to fewer large sequences (genomic regions). In general, WU BLAST was found to be the most efficient sequence comparison tool. These approaches illustrate the power of ESTs in understanding gene expression. Efficient computational analysis of ESTs (such as the two tools described) will be vital to understanding the complexity of gene expression as more high-throughput EST data is made available via advances in molecular sequencing technologies, such as the current next-generation approaches

Assessing architectural evolution: A case study

This is the post-print version of the Article. The official published can be accessed from the link below - Copyright @ 2011 SpringerThis paper proposes to use a historical perspective on generic laws, principles, and guidelines, like Lehman’s software evolution laws and Martin’s design principles, in order to achieve a multi-faceted process and structural assessment of a system’s architectural evolution. We present a simple structural model with associated historical metrics and visualizations that could form part of an architect’s dashboard. We perform such an assessment for the Eclipse SDK, as a case study of a large, complex, and long-lived system for which sustained effective architectural evolution is paramount. The twofold aim of checking generic principles on a well-know system is, on the one hand, to see whether there are certain lessons that could be learned for best practice of architectural evolution, and on the other hand to get more insights about the applicability of such principles. We find that while the Eclipse SDK does follow several of the laws and principles, there are some deviations, and we discuss areas of architectural improvement and limitations of the assessment approach

Unsupervised Bilingual POS Tagging with Markov Random Fields

In this paper, we give a treatment to the problem of bilingual part-of-speech induction with parallel data. We demonstrate that naïve optimization of log-likelihood with joint MRFs suffers from a severe problem of local maxima, and suggest an alternative – using contrastive estimation for estimation of the parameters. Our experiments show that estimating the parameters this way, using overlapping features with joint MRFs performs better than previous work on the 1984 dataset.

Alignments of mitochondrial genome arrangements: Applications to metazoan phylogeny

Mitochondrial genomes provide a valuable dataset for phylogenetic studies, in particular of metazoan phylogeny because of the extensive taxon sample that is available. Beyond the traditional sequence-based analysis it is possible to extract phylogenetic information from the gene order. Here we present a novel approach utilizing these data based on cyclic list alignments of the gene orders. A progressive alignment approach is used to combine pairwise list alignments into a multiple alignment of gene orders. Parsimony methods are used to reconstruct phylogenetic trees, ancestral gene orders, and consensus patterns in a straightforward approach. We apply this method to study the phylogeny of protostomes based exclusively on mitochondrial genome arrangements. We, furthermore, demonstrate that our approach is also applicable to the much larger genomes of chloroplasts