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Thesis

Active learning for sequential screening and classification of molecular and genomic data

Authors: Walker, Megon Jarmaine (2006)

Understanding molecular interactions is at the core of computational biology and includes problems such as characterizing protein-protein, protein-small molecule, protein-DNA, and Protein-RNA binding events. These interactions are often elucidated by expensive and time-consuming assays during which candidate binders are screened against a target. The main aim of this dissertation is to improve the speed, cost, and overall efficiency of screening assays in the context of drug design and molecular systems biology. Sequential screening is an iterative process of experimentation and model refinement. Target binding activity is determined for samples of putative binders, results are used to update a classification model, and subsequent binding experiments are performed based on knowledg...

Article

Predicting gene structure in eukaryotic genomes

Authors: Allen, Jonathan Edward (2006)

Obtaining the complete set of proteins for each eukaryotic organism is an important step in the quest to understand how life evolves and functions. The complex physiology of eukaryotic cells, however, makes direct observation of proteins and their parent genes difficult to achieve. An organism's genome provides the raw data that contains the set of instructions for generating the complete set of proteins, providing the potential to obtain a complete list of proteins without having to rely exclusively on direct observations in the cell. Computational gene prediction systems, therefore, play an important role in compiling sets of putative proteins for each sequenced genome. This dissertation addresses the problem of computational gene prediction in eukaryotic genomes, presenting a fr...

Thesis

Regulation of genomic stability by Saccharomyces cerevisiae sirtuins Hst3p and Hst4p

Authors: Celic, Ivana (2006)

The Sir2 proteins, also known as sirtuins, represent a large and highly conserved family of NAD+-dependent protein deacetylases that control various fundamental biological proceses. The baker’s yeast, Saccharomyces cerevisiae, has five members of this family, Sir2p and Hst1-4p, important for regulation of transcriptional silencing and genomic stability. Hst3p and Hst4p are two redundant sirtuins with the major role in maintenance of genomic stablity. They control genomic stability by regulating the level of acetylation of histone H3 lysine 56. This residue, present in the core of the nucleosome surface, is acetylated during the S phase of the cel cycle and contributes to the repair proceses active during DNA replication. At the end of the S phase, K56 of histone H3 is deacetylated ...