Typewritten copy Includes bibliographical references

"January 2004" / Includes bibliographical references (leaves 178-201) / Accompanying CD-ROM contains raw data for the thesis / Systems requirements for accompanying CD-ROM: IBM PC or compatible; CD-ROM drive; Adobe acrobat reader / xv, 201 leaves : ill. (some col.), plates (col.) ; 30 cm. + 1 CD-ROM (col. ill. ; 4 3/4 in.) / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 2004

No description available.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (M.A.)--Central Connecticut State University, 2003. / Thesis advisor: Thomas R. King. " ... in partial fulfillment of the requirements for the degree of Master of Arts in General Biology." Includes bibliographical references (leaves 42-43). Also available via the World Wide Web.

Thesis (Ph. D.)--University of Queensland, 2003. / Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 1988.

Thesis (M.S.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains vi, 38 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 35-37).

The rapid development of high-throughput sequencing technology provides a new chance to extend the scale and resolution of genomic research. How to efficiently and accurately call genetic variants in single base level (germline single nucleotide polymorphisms (SNPs) or somatic single nucleotide variants (SNVs)) is the fundamental challenge in sequencing data analysis, because these variants reported to influence transcriptional regulation, alternative splicing, non-coding RNA regulation and protein coding. Many applications have been developed to tackle this challenge. However, the shallow depth and cellular heterogeneity make those tools cannot attain satisfactory accuracy, and the huge volume of sequencing data itself cause this process inefficient. In this dissertation, firstly the performance of prevalent reads aligners and SNP callers for second-generation sequencing (SGS) is evaluated. And due to the high GC-content, the significantly lower coverage and poorer SNP calling performance in the regulatory regions of human genome by SGS is investigated. To enhance the capability to call SNPs, especially within the lower-depth regions, a fast and accurate SNP detection (FaSD) program that uses a binomial distribution based algorithm and a mutation probability is proposed. Based on the comparison with popular software and benchmarked by SNP arrays and high-depth sequencing data, it is demonstrated that FaSD has the best SNP calling accuracy in the aspects of genotype concordance rate and AUC. Furthermore, FaSD can finish SNP calling within four hours for 10X human genome SGS data on a standard desktop computer. Lastly, combined with the joint genotype likelihoods, an updated version of FaSD is proposed to call the cancerous somatic SNVs between paired tumor and normal samples. With extensive assessments on various types of cancer, it is demonstrated that no matter benchmarked by the known somatic SNVs and germline SNPs from database, or somatic SNVs called from higher-depth data, FaSD-somatic has the best overall performance. Inherited and improved from FaSD, FaSD-somatic is also the fastest somatic SNV caller among current programs, and can finish calling somatic mutations within 14 hours for 50X paired tumor and normal samples on normal server. / published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

This thesis describes the development of: (i) an automatic chromosome analysis system capable of producing to a high degree of accuracy and consistency a correct classification for damaged chromosomes at a low cost and (ii) a parallel computer system to enable more rapid chromosome analysis. Chromosomes can be examined in a cytogenetics laboratory for a variety of purposes including an assessment of the affects of ionisation exposure on the genetic code of the cell. Scoring of chromosome aberrations caused by ionisation of radiation exposure, is possible by detecting dicentric chromosomes. In addition this approach provides a good biological radiation measure (dosimeter). However, currently manual methods are extremely time consuming and expensive with respect to labour costs. For the low radiation doses it is necessary to analyse a large number of chromosomes to identify a small number of damaged ones to score the number of aberrations. Consequently, the main objective of this research programme is to develop a rapid, low cost, and accurate automated chromosome analysis system. This research has concentrated solely on scoring dicentric chromosome since their characteristic shape is relatively easy to recognise in most cases and they most commonly created by exposure to radiation. The methods and theories considered in this thesis concerns chromosome image selection by automatic segment extraction using of the following: grey levels; image extraction by seed aggregation, a two dimensional function, a moment algorithm, for chromosome orientation; chromosome centreline determination; rapid detection of the chromosome centromere of the candidate. The new methods developed by the author and presented herein concern three steps or processes in automatic chromosome analysis. These include (i) a new segmentation scheme (ii) automatic selection the cell threshold grey scale level and (iii) the design a new methods capable of detecting bent chromosome with rapid determination the chromosome centromere. Parallel processing using the processor farm technique has been successfully developed to enable a more rapid chromosome classification system. The techniques described have been carefully tested and evaluated and have clearly demonstrated the potential application of the analysis methods by the author.