Genomics and bioinformatics approaches to functional gene annotation

Biomedical research has been undergoing a quasi-revolution with the dawn of the genomics era. The flood of sequence data from the various genome projects, the task of cataloging the entire coding portion of a genome instead of identifying and characterizing individual genes, as well as technical demands accompanying these developments have posed great challenges to the research community. Although the entire human genome sequence has been virtually recorded, fundamental issues remain about the precise number of protein coding genes, as well as their functional characterization. Available resources for the study of human gene function include large genome annotation pipelines, expression profiling data, and protein interaction screens. To gain biological insights from this maze of data, one must both find mechanisms to organize the information and assess the quality of the results. This thesis focuses on the functional annotation of sparsely characterized human genes and their encoded proteins. The work includes four stages: I. Gene expression profiling II. Assessment of the level of characterization of human genes III. Projection of protein networks from lower eukaryotes onto human IV. Integration of computational and experimental results for data mining. Initially, a cross-platform comparison for a set of gene expression profiling techniques was carried out to compare the performance of cutting-edge high-throughput methods and conventional approaches in terms of sensitivity, reliability, and throughput. In this study, we demonstrated that correlation between the different methods was poor and thus multi-technique validation was justified. Nonetheless, the strongest correlation between the new reference data in our report, i.e., a collection of traditional Northern blots, was observed with microarray-based technologies. The assessment of the level of functional characterization of human genes was addressed in the second study, where we developed a scoring system to quantify the annotation status of each human ...