Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 96-103).

Some upstream open reading frames (uORFs) regulate gene expression (i.e. they are functional) and can play key roles in keeping organisms healthy. However, how uORFs are involved in gene regulation is not het fully understood. In order to get a complete view of how uORFs are involved in gene regulation, it is expected that a large number of functional uORFs are needed. Unfortunately , lab experiments to verify that uORFs are functional are expensive. In this thesis, for the first time, the use of inductive logic programming (ILP) is explored for the task of learning which uORFs regulate gene expression in the yeast Saccharomyces cerevisiae. This work is directed to help select sets of candidate functional uORFs for experimental studies. With limited background knowledge, ILP can generate hypotheses which make the search for novel functional uORFs 17 times more efficient than random sampling. Adding mRNA secondary structure to the background knowledge results in hypotheses with significantly increased performance. This work is the first machine learning work to study both uORFs and mRNA secondary structures in the context of gene regulation. Using a novel combination of knowledge about biological conservation, gene ontology annotations and genes' response to different conditions results in hypotheses that are simple, informative, have an estimated sensitivity of 81% and provide provisional insights into biological characteristics of functional uORFs. The hypotheses predict 299 further genes to have 450 novel functional uORFs. A comparison with a related study suggests that 8 of these predicted functional uORFs (from 8 genes) are strong candidates for experimental studies.

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Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 89-99).

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [73]-84).

This study has successfully identified transcripts differentially expressed in the salivary gland and midgut and provides candidate genes that are critical to response to parasite invasion. Furthermore, an open-source Glossina resource (G-ESTMAP) was developed that provides interactive features and browsing of functional genomics data for researchers working in the field of Trypanosomiasis on the African continent.

This study has successfully identified transcripts differentially expressed in the salivary gland and midgut and provides candidate genes that are critical to response to parasite invasion. Furthermore, an open-source Glossina resource (G-ESTMAP) was developed that provides interactive features and browsing of functional genomics data for researchers working in the field of Trypanosomiasis on the African continent.

Thesis (Ph.D. in Biophysics & Genetics, Human Medical Genetics Program) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 123-147). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Philosophiae Doctor - PhD / This study has successfully identified transcripts differentially expressed in the salivary gland and midgut and provides candidate genes that are critical to response to parasite invasion. Furthermore, an open-source Glossina resource (G-ESTMAP) was developed that provides interactive features and browsing of functional genomics data for researchers working in the field of Trypanosomiasis on the African continent. / South Africa

Short open reading frames (sORFs) are codon sequences with a start and stop codon within atmost 100 codons. Cells produce many transcripts from them and some sORFs have been found to have function. sORFs have been associated with embryogenesis, myogenesis, immunity and various diseases including cancers. Cell culture screening is a common method to study function in sORFs. By inserting mutations in known sORF locations one can affect their translation by removing start codons, inserting premature stop codons, or removing native stop codons. A new tool set to do this isCRISPR technology, where single guide RNA (gRNA) can be used to make more precise genome edits. Unfortunately, such design is nontrivial and suggests a lot of variants for testing. It results in a back-and-forth testing process involving different available design tools. In this project, a comprehensive way was developed to see and iterate over the many test combinations. This intends to ease the process and decrease the likelihood for errors. The developed solution is a tool that integrates the currently best design tools. It also introduces a method in the form of a new quality summary score that can evaluate the estimated outcomes of the various designed guide variants. The tool was tested, and it was found that the score simplifies and amplifies the earlier usedscore methods. The pipeline is simple to install and use, integrates the currently most actively developed tools, and an installation is as future proof as can be made in a rapidly evolving field.