Planning, management and analysis of DNA microarray data aiming at discovery of biomarkers for diagnosis and prognosis of human cancers.

Author(s)

Ana Carolina Quirino Simões

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Matemática e Estatística (IME/SBI)
• Defense date: 2009-05-12

Examining board members

Aline Maria da Silva; Helena Paula Brentani; Roberto Hirata Junior; Wilson Araújo da Silva Junior; Mari Cleide Sogayar

• Advisor: Aline Maria da Silva; Eduardo Jordao Neves

Abstract

In this PhD Thesis, we present our strategies to the development of a mathematical and computational environment aiming the analysis of large-scale microarray datasets. The analyses focused mainly on the identification of molecular markers for diagnosis and prognosis of human cancers. Here we show the results of several analyses implemented using this environment, which led to the development of a computational tool for automatic annotation of DNA microarray platforms and a tool for tracking the analysis within R environment. We also applied eXtreme Programming (XP) as a tool for planning and management of gene expression analyses projects. All data sets were obtained by our collaborators using two different microarray platforms. The first is enriched in non-coding human sequences, particularly intronic sequences. The second one represents exonic regions of human genes. Using the first platform, we evaluated gene expression profiles of prostate and kidney human tumors. Applying SAM to prostate tumor data revealed 49 potential molecular markers for prognosis of this disease. Gene expression in samples of sarcomas, epidermoid carcinomas and head and neck epidermoid carcinomas was investigated using the second platform. A set of 12 genes were identified as potential biomarkers for local aggressiveness and metastasis in sarcoma. In addition, the analyses of data obtained from head and neck epidermoid carcinomas allowed the identification of 7 potential biomarkers for lymph-nodal metastases. (AU)