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Computational analysis of gene expression in the parasite protostome Schistosoma mansoni

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Author(s):
Thiago Motta Venancio
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Matemática e Estatística (IME/SBI)
Defense date:
Examining board members:
Sergio Verjovski de Almeida; Alan Mitchell Durham; Glória Regina Franco; Arthur Gruber; Georgios Joannis Pappas Junior
Advisor: Sergio Verjovski de Almeida; João Carlos Setubal
Abstract

Schistosoma mansoni is one of the causative agents of schistosomiasis, a neglected infectious disease which affects millions of people worldwide. It is a dioecious parasitic platyhelminth, with a complex life cycle composed of six stages. In the past five years, large scale sequencing projects have generated a reasonable amount of expressed sequence tag (EST) data that can still be better explored. The goal of this thesis is to computationally analyze the S. mansoni gene expression, under three different focuses: (i) DNA microarrays, for which we describe the design and data analyses of a cDNA (4,600 elements) and an oligonucleotide (44,000 elements) platform. We also describe the implementation of several analysis tools which are widely used in our group. Our microarrays are being used in several projects, such as the study of parasite response to drugs and hormones, as well as its gene expression pattern during the life cycle. (ii) In silico identification of possible trans acting natural sense-antisense pairs, potentially important in gene regulation. (iii) Analyses of the available EST dataset under an evolutionary perspective. We have found interesting genes such as a possible angiogenesis inhibitor and a regulator of the mevalonate pathway, known to be essential for egg production; eggs are the main cause of morbidity of schistosomiasis. The results reported here contribute to the understanding of the complex biology underlying the S. mansoni life cycle and to accelerate the search for future possibilities of treatment. (AU)