Browsing by Author "Moura, Gabriela"
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- An Application for Studying Tandem Repeats in Orthologous GenesPublication . Lousado, José; Oliveira, José; Moura, Gabriela; Santos, ManuelSeveral authors have being suggesting that the occurrence of amino acids repeats in some genes are implied in human diseases. We aim to investigate if these repetitions, which one can observe in humans, also exist in orthologous genes of several organisms, and how they have evolved along time. However, for this kind of study, it is necessary to use different databases and computation methods that are not integrated in any specific tool. In this paper, we present a bioinformatics application, supported by Web Services, that allows to conduct comparative analysis studies for various organisms, along the evolutionary chain.
- Analysing the Evolution of Repetitive Strands in GenomesPublication . Lousado, José; Oliveira, José; Moura, Gabriela; Santos, ManuelThe analysis of genomes and proteomes of the various organisms allow us to observe its behaviour in the evolution of species. In this study, we focus our attention on a particular aspect of this analysis: the conservation of specific codon and amino acid repetitions in orthologous genes belonging to eukaryotic organisms that are representative of different stages of species evolution. Since it is known that these repeats in humans are the cause of various neurodegenerative diseases, among others, this study help explaining if there is conservation or repression of such repetitions in the specialization process, and if there is any relationship between these repetitions and diseases in advanced live beings.
- Codon-triplet context unveils unique features of the Candida albicans protein coding genomePublication . Moura, Gabriela; Lousado, José; Pinheiro, Miguel; Carreto, Laura; Silva, Raquel; Oliveira, José; Santos, ManuelBACKGROUND: The evolutionary forces that determine the arrangement of synonymous codons within open reading frames and fine tune mRNA translation efficiency are not yet understood. In order to tackle this question we have carried out a large scale study of codon-triplet contexts in 11 fungal species to unravel associations or relationships between codons present at the ribosome A-, P- and E-sites during each decoding cycle. RESULTS: Our analysis unveiled high bias within the context of codon-triplets, in particular strong preference for triplets of identical codons. We have also identified a surprisingly large number of codon-triplet combinations that vanished from fungal ORFeomes. Candida albicans exacerbated these features, showed an unbalanced tRNA population for decoding its pool of codons and used near-cognate decoding for a large set of codons, suggesting that unique evolutionary forces shaped the evolution of its ORFeome. CONCLUSION: We have developed bioinformatics tools for large-scale analysis of codon-triplet contexts. These algorithms identified codon-triplets context biases, allowed for large scale comparative codon-triplet analysis, and identified rules governing codon-triplet context. They could also detect alterations to the standard genetic code.
- Exploiting Codon-Triplets Association for Genome Primary Structure AnalysisPublication . Lousado, José; Oliveira, José; Moura, Gabriela; Santos, ManuelAbstract— The way evolution shapes the arrangement of synonymous codons within open reading frames (ORF) for fine tuning mRNA decoding efficiency is not yet understood. Since the ribosome has 3 tRNA binding sites, the context of triplets should be relevant to decoding fidelity and efficiency. We have developed a software application for large-scale analysis of codon-triplet associations to shed new light into this problem. The developed algorithms identify codon-triplets context biases, allowing for large scale comparative codon-triplet analysis and for identification of alterations to the standard genetic code.
- GeneSplit - Uma Aplicação para o Estudo de Associações de Codões e de Aminoácidos em ORFeomasPublication . Lousado, José; Oliveira, José; Moura, Gabriela; Santos, ManuelA descodificação de genomas, em particular do genoma humano, constituiu um marco cientifico extremamente importante nas últimas décadas e veio abrir caminho a novas áreas de investigação como a genómica e a proteómica. Espera-se que os avanços de conhecimento introduzidos por estas áreas tragam novas perspectivas sobre a forma como são diagnosticadas e tratadas muitas das doenças actuais, nomeadamente as que têm uma associação clara com disfunções ao nível do genotipo. Neste artigo, apresentamos uma aplicação computacional que permite estudar associações anormais de codões em orfeomas, i.e. em sequências responsáveis pela construção de proteínas. Os resultados biológicos já obtidos mostram claramente a utilidade prática do software desenvolvido, que é disponibilizado de uma forma pública para a comunidade científica
- Large scale comparative genomics of codon contextPublication . Lousado, José; Moura, Gabriela; Pinheiro, Miguel; Oliveira, José; Santos, ManuelThe efficiency of protein synthesis is highly dependent on codon usage and codon context. Indeed, the choice of particular synonymous codons is constrained by neighbour codons (codon context) to optimize mRNA decoding speed and accuracy. This is related to spatial (steric) effects created by the need to accommodate 3 tRNAs in the ribosome A-, P- and E-sites. Since these tRNAs interact with each other, with their cognate codons and with various structural domains of rRNAs, the structure of the 6 nucleotide RNA helix formed by the anticodon-codon interactions is strongly int1uenced by the type of codons and tRNAs present in the ribosome decoding centre. To ensure proper tRNA selection and correct codon decoding the rRNA monitors the structure of the codon-anticodon RNA helix. We hypothesized that large scale comparative analysis of 3 consecutive codons, corresponding to the ribosome A-, P- and E-sites codons, would unveil novel codon biases and "bad" codon combinations that are error prone. For this, we have built a software package that counts codon triplets in complete assemblies of open reading frames (ORFeomes) and used the ORFeome sequences of 12 fungal species, including Aspergillus fumigatus, Saccharomyces cerevisiae, and Candida albicans to validate our working hypothesis. We have used data mining methodologies to explore this large dataset of 220,000 combinations of 3 consecutive codons, and extracted the most biased contexts. The data showed that three-codon contexts are species-specific, although major context rules could also be found. Interestingly, biases introduced at DNA replication and transcription levels, namely trinucleotide repeats, play an important role in the evolution of ORFeomes. Candida albicans revealed unique features and very strong context biases. For example, codon triplet biases is much stronger in C. albicans than in other species and it has a very high number of consecutive codon repeats, which comprise up to 6% of the total ORFeome