Francisco Prosdocimi

Genetic algorithm for analysis of mutations in Parkinson's disease

OBJECTIVE Mitochondrial genetics has unique features that impede analysis of the biological significance of mitochondrial mutations. Simple searches for differences in total mutational load between normal and pathological samples have been frequently unrewarding, raising the possibility that more complex patterns of mutations may be responsible for some conditions. We explore this possibility in the context of Parkinsons disease (PD). METHODS AND MATERIALS We report the development of a modified genetic algorithm suited for detection of biologically meaningful patterns of mitochondrial mutations. The algorithm is applied to a database of mutations derived from biological samples, and verified by the use of shuffled data, and repeated leave-one-out testing. RESULTS It is possible to derive, from a very small sample, multiple accurate classifier functions that correlate with biological features. The methodology is validated statistically through experiments with fabricated data. CONCLUSION This algorithm might be generally applicable to conditions where interactions among multiple mitochondrial DNA mutations are important. The patterns embodied in the classifier functions obtained should be the subject of further experimental study.

Survey of genome organization and gene content of Corynebacterium pseudotuberculosis

Corynebacterium pseudotuberculosis is an intracellular pathogen that causes Caseous lymphadenitis (CLA) disease in sheep and goats. The widespread occurrence and the economic importance of this pathogen have prompted investigation of its pathogenesis. We used a genomic library of C. pseudotuberculosis to generate 1440 genomic survey sequences (GSSs); these were analyzed in silico with bioinformatics tools, using public databases for comparative analyses. We employed non-redundant unique sequences as a query for BLAST searches against the genome, the translated genome and the proteome of four other Corynebacterium species that have been completely sequenced. We were able to characterize approximately 8% of the genome of C. pseudotuberculosis, including previously undescribed functional group genes, based on the COG database; the GSSs classification into categories gave 13% information storage and processing, 14% cellular processes and 23% metabolism. We found a close relation between C. pseudotuberculosis and C. diphtheriae conserved-gene synteny in Corynebacteria species.

Clustering of Schistosoma mansoni mRNA Sequences and Analysis of the Most Transcribed Genes: Implications in Metabolism and Biology of Different Developmental Stages

The study of the Schistosoma mansoni genome, one of the etiologic agents of human schistosomiasis, is essential for a better understanding of the biology and development of this parasite. In order to get an overview of all S. mansoni catalogued gene sequences, we performed a clustering analysis of the parasite mRNA sequences available in public databases. This was made using softwares PHRAP and CAP3. The consensus sequences, generated after the alignment of cluster constituent sequences, allowed the identification by database homology searches of the most expressed genes in the worm. We analyzed these genes and looked for a correlation between their high expression and parasite metabolism and biology. We observed that the majority of these genes is related to the maintenance of basic cell functions, encoding genes whose products are related to the cytoskeleton, intracellular transport and energy metabolism. Evidences are presented here that genes for aerobic energy metabolism are expressed in all the developmental stages analyzed. Some of the most expressed genes could not be identified by homology searches and may have some specific functions in the parasite.

Diet as a pressure on the amino acid content of proteomes

Whether diet has been influencing the genomic and proteomic constitution of the organisms along the evolution is an interesting and not answered question. Here, we investigate the hypothesis that essential amino acids – the ones that are not produced by the organisms – have being replaced in proteins by non-essential ones. We compare the amino acid composition of the proteome from human, worm and fly, that cannot synthesize all amino acids, with the ones from plant, baker yeast and budding yeast, capable to synthesize all of them. The analysis was made with 190,074 proteins composed of 87,175,891 amino acids. Our data seems to evidence a little bias on the usage of non-essential amino acids by the metazoan organisms, except for the worm. Thus, the preliminary results shown here support the thesis that non-essential ones have replaced essential amino acids.