Au cours des dernières décennies, les avancées techniques dans la biologie moléculaire telles que les projets de séquençage de génome ont eu pour conséquence un accroissement du volume des banques de données biologiques. Parmi ces données, des séquences présentent des motifs similaires entre eux, répétés de façon juxtaposée, appelés répétitions en tandem. L'objectif de cette thèse est de comprendre l'existence de ces répétitions dans les séquences protéiques via une analyse à grande échelle. / Over the last decades, technical advances in molecular biology such as the genome sequencing projects led to a huge increase of data in the biological databanks. Among them, there are particular motifs which are adjacently repeated and similar between them, called tandem repeats. The purpose of this thesis is to understand the existence of these repeats in protein sequences through a large-scale analysis.

Sequence analysis and structure analysis are two of the fundamental areas of bioinformatics research. This dissertation discusses, specifically, protein structure related problems including protein structure alignment and query, and genome sequence related problems including haplotype reconstruction and genome rearrangement. It first presents an algorithm for pairwise protein structure alignment that is tested with structures from the Protein Data Bank (PDB). In many cases it outperforms two other well-known algorithms, DaliLite and CE. The preliminary algorithm is a graph-theory based approach, which uses the concept of \stars" to reduce the complexity of clique-finding algorithms. The algorithm is then improved by introducing \double-center stars" in the graph and applying a self-learning strategy. The updated algorithm is tested with a much larger set of protein structures and shown to be an improvement in accuracy, especially in cases of weak similarity. A protein structure query algorithm is designed to search for similar structures in the PDB, using the improved alignment algorithm. It is compared with SSM and shows better performance with lower maximum and average Q-score for missing proteins. An interesting problem dealing with the calculation of the diameter of a 3-D sequence of points arose and its connection to the sublinear time computation is discussed. The diameter calculation of a 3-D sequence is approximated by a series of sublinear time deterministic, zero-error and bounded-error randomized algorithms and we have obtained a series of separations about the power of sublinear time computations. This dissertation also discusses two genome sequence related problems. A probabilistic model is proposed for reconstructing haplotypes from SNP matrices with incomplete and inconsistent errors. The experiments with simulated data show both high accuracy and speed, conforming to the theoretically provable e ciency and accuracy of the algorithm. Finally, a genome rearrangement problem is studied. The concept of non-breaking similarity is introduced. Approximating the exemplar non-breaking similarity to factor n1..f is proven to be NP-hard. Interestingly, for several practical cases, several polynomial time algorithms are presented.

Student Number : 0314429G - MSc research report - School of Molecular and Cell Biology - Faculty of Science / Tomato (Lycopersicon esculentum) is a horticultural commodity of great economic importance in many parts of the world, including South Africa. A previous study identified a new begomovirus, Tomato curly stunt virus (ToCSV), as the causative virus of a new and potentially devastating disease of tomatoes in South Africa. In this study, symptomatic plants, suspected of infection with an uncharacterized ToCSV isolate (01/2521) were collected for screening from Pietermaritzburg, South Africa. A host range study was conducted with the original ToCSV isolate (99/0631). Two small DNA molecules (1449 nts and 755 nts) were found associated with ToCSV [01/2521] using near-full length primers AL1c2745 and PAR1v32 specific for ToCSV. A single small DNA molecule (842 nts) was also found in association with the original ToCSV isolate. Nucleotide sequence analysis revealed that the two small DNA molecules (1449bp and 755bp) have no significant nucleotide sequence identity (less than 20%) with any known begomovirus. The 842bp molecule has the most significant nucleotide sequence identity (48%) to that of ToCSV (AF261885), while less than 20% nucleotide sequence identities were found when compared with other begomoviruses. Nucleotide sequence alignment of the 842bp DNA molecule to the ToCSV sequence, showed that this small DNA molecule is a chimeric molecule that could have arisen through recombination, partly from the coding regions of the ToCSV genome, but the rest of the molecule is of unknown origin. All three small DNA molecules identified in this study were compared to some known begomovirus associated subgenomic molecules and satellite molecules, and sequence identities of less than 20% were found. To our knowledge, this is the first report of a small DNA molecule found associated with the ToCSV genome. The complete genome sequence of ToCSV [01/2521] was not determined. Based on the results we obtained from the host range study, all the chosen test plants are not susceptible to ToCSV infection. The infectivity of all the small molecules identified in this study, is currently being investigated.

O gênero Nocardia é composto por bactérias gram-positivas e filamentosas, que normalmente só causam doença em indivíduos imunocomprometidos. No entanto, certo número de infecções por nocardia têm sido relatados em pacientes imunocompetentes. Nos últimos anos, observou-se um aumento da frequência de infecções por Nocardia spp. e, com o aumento do número de espécies descritas, a identificação correta tem sido de difícil obtenção mas de grande importância para a aplicação do tratamento correto e elucidação epidemiológica. O objetivo deste estudo foi caracterizar, por métodos fenotípicos e moleculares, 72 isolados de Nocardia spp. de interesse médico, avaliando as metodologias para elaborar um algoritmo de identificação. Os isolados foram provenientes da Micoteca do Instituto de Medicina Tropical de São Paulo e da rotina do Núcleo de Tuberculose e Micobacterioses do Instituto Adolfo Lutz. Os isolados foram identificados por testes fenotípicos, identificação molecular por análise de restrição (PRA-hsp65), sequenciamento dos genes hsp65 e 16S rRNA e MALDI-TOF MS (Matrix-associated laser desorption time of flight mass spectrometry). O perfil de suscetibilidade foi analisado pelo método de Concentração Inibitória Mínima (MIC) e disco difusão (DD), com os fármacos: amicacina, ciprofloxacina, minociclina, tobramicina, amoxacilina+ácido clavulânico, imipenem e sulfametoxazol+trimetoprim. Os resultados revelaram que a identificação fenotípica foi insuficiente para definir as espécies. Apenas 24 (33,4%) isolados tiveram identificação fenotípica concordante com o sequenciamento do gene 16S rRNA. Na analise feita pela técnica de PRA-hsp65 foram observados 20 (27,8%) N. brasiliensis, seis (8,3%) isolados de outras espécies de nocardias e 38 (52,8%) foram considerados novos padrões (NP). Foi detectado um isolado misto e em cinco isolados não foi obtido produto de amplificação. O sequenciamento do gene hsp65 proporcionou a identificação de 51 isolados como Nocardia, 14 foram identificados como pertencentes a outros gêneros, dos quais, um apresentou mistura de nocardia e micobactéria, sendo identificado como Mycobacterium abscessus no gene hsp65 (análise in silico) e N. otitidiscaviarum no gene 16S rRNA. Sete isolados não foram sequenciados devido à ausência de amplificação do fragmento. Os isolados analisados através do sequenciamento do gene 16S rRNA, foram identificados como Nocardia (57-79,2%), Gordonia (7-9,7%), Rhodoccocus (3-4,2%), Tsukamurella (2-2,8%), Mycobacterium (2-2,8%) e Streptomyces (1-1,3%). Para a análise de MALDI-TOF MS foi observado que, dos 72 isolados estudados, 49 foram identificados como Nocardia, 11 como pertencentes a outros gêneros e 12 amostras não puderam ser identificadas devido aos valores de leitura não serem adequados para análise. Pela primeira vez o corante resazurina foi utilizado para leitura de MIC de Nocardia sp. Entre os fármacos testados através do MIC, os que apresentaram maior sensibilidade foram amicacina (100%) e tobramicina (84%). As maiores resistências foram encontradas com os fármacos sulfametoxazol+trimetoprim (76%) e imipenem (54%). Devido à ausência de critérios interpretativos de disco difusão para o gênero Nocardia, foi elaborado um critério para o presente estudo. Os resultados obtidos no teste de DD mostraram 100% de sensibilidade para os fármacos amicacina, minociclina e sulfametoxazol+trimetroprim. Os isolados apresentaram a maior porcentagem de resistência ao fármaco ciprofloxacina (64%). Comparando os resultados de DD com os obtidos no MIC, observamos que os fármacos ciprofloxacina, imipenem e sulfametoxazol+trimetoprim apresentaram porcentagem de discordância acima de 20%. O fármaco sulfametoxazol+trimetoprim teve a maior discordância (>75%), com elevada porcentagem de isolados resistentes na MIC, mas baixa porcentagem de resistência em DD. O único fármaco com 100% de concordância entre os resultados foi amicacina. Foi elaborado um algoritmo de identificação que utiliza técnicas fenotípicas para triagem para diferenciar nocardias de outros gêneros. A identificação por PRA-hsp65 será útil na rotina de laboratório de micobactérias como identificação presuntiva. A identificação definitiva das espécies deve ser obtida pelo sequenciamento do gene 16S rRNA. / The genus Nocardia comprises filamentous gram-positive bacteria that usually cause disease only in immunocompromised individuals. However, a number of Nocardia infections have been reported in immunocompetent patients. Overall, it has been reported in the recent years an increased frequency of infections caused by Nocardia spp. due to an also increasing number of species, making the correct identification of the species more difficult. Correct identification assumes a major importance with respect to antimicrobial treatment\'s choice as well a for epidemiological investigation purposes. The objective of this study was to characterize by phenotypic and molecular methods 72 isolates of Nocardia spp. of medical interest, designing the methodologies for an identification algorithm. The isolates were obtained from the fungal collection of the Tropical Medicine Institute of São Paulo and the routine service of the Tuberculosis and Mycobacteriosis Center of the Adolfo Lutz Institute. The isolates were identified by phenotypic testing, molecular identification by restriction analysis (PRA-hsp65), hsp65 and 16S rRNA genes sequencing, and MALDI-TOF MS (matrix-associated laser desorption time-of-flight mass spectrometry). The susceptibility profile was analyzed by the Minimum Inhibitory Concentration method (MIC) and disk diffusion (DD), with the following drugs: amikacin, ciprofloxacin, minocycline, tobramycin, amoxicillin+ clavulanic acid, imipenem and sulfamethoxazole trimethoprim. The results showed that the phenotypic identification was insufficient to define the species. Only 24 (33.4%) of the isolates had phenotype identification that was concordant with the 16S rRNA gene sequencing. In the analysis made with the PRA-hsp65 technique were observed 20 (27.8%) N. brasiliensis and six (8.3%) isolates from other species of Nocardia spp., while 38 isolates (52.8%) were considered as new standards (NP). Also by this technique a mixed isolate was detected and an amplification product was not obtained in five isolates. The hsp65 gene sequencing provided identification of 51 isolates as Nocardia, 14 were identified as belonging to other genera, one of them being identified either as Mycobacterium abscessus by in silico analysis of the hsp65 gene and as N. otitidiscaviarum by the 16S rRNA gene sequencing. Seven isolates were not sequenced due to the absence of the amplified fragment. The isolates analyzed by 16S rRNA gene sequencing were identified as Nocardia (57 to 79.2%), Gordonia (7 to 9.7%), Rhodoccocus (3 to 4.2%), Tsukamurella (2-2, 8%), Mycobacterium (2 to 2.8%) and Streptomyces (1-1.3%). By MALDI-TOF MS analysis of the 72 isolates, 49 were identified as Nocardia, 11 were identified as belonging to other genera and 12 isolates could not be identified because the samples provided reading values that were inadequate for analysis. For the first time, to our knowledge, the resazurin dye was used to determine the MICs of Nocardia sp. Among the drugs tested, the most sensitives were amikacin (100%) and tobramycin (84%). The higher resistances were found with trimethoprim-sulfamethoxazole (76%) and imipenem (54%). Due to the absence of establishe criteria for the interpretation of the disk diffusion assay with Nocardia, we designed a specific criterion for this study. The results obtained in the DD test showed 100% sensitivity for the drugs amikacin, minocycline and trimethoprim-sulfamethoxazole. The isolates showed the highest percentage of resistance to ciprofloxacin drug (64%). Comparing the results with those obtained with DD and MIC, we observed that ciprofloxacin, imipenem and sulfamethoxazole-trimethoprim showed a percentage of disagreement above 20%. The sulfamethoxazole-trimethoprim drug had the highest discrepancy (> 75%), with high percentage of resistant isolates with MIC but low percentage of resistance in DD. The only drug with 100% agreement between the both results was amikacin. We designed a recognition algorithm using phenotyping techniques to screen and differentiate nocardias from other genera. The identification by PRA-hsp65 will be useful in routine mycobacteria laboratory as a presumptive identification tool. The final identification of the species should be obtained by sequencing the 16S rRNA gene.

Mak Chun-yin. / "February 2001." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 156-169). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

by Ray, Kit Ng. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 112-121). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgments --- p.iv / Abbreviations --- p.x / List of Figures --- p.xii / List of Tables --- p.xiv / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- Hepatitis B Virus (HBV) --- p.1 / Chapter 1.2 --- Hepatitis B Virus X Protein (HBx) --- p.5 / Chapter 1.2.1 --- The Genomic Structure of HBx --- p.5 / Chapter 1.2.2 --- The HBx Protein Structure --- p.6 / Chapter 1.2.3 --- Subcellular Localization of HBx --- p.7 / Chapter 1.2.4 --- Possible Functions of HBx --- p.8 / Chapter 1.3 --- Etiology of Hepatocellular Carcinoma (HCC) --- p.12 / Chapter 1.4 --- Relationship between HCC and HBx --- p.13 / Chapter 1.5 --- Aims of Study --- p.14 / Chapter 1.6 --- The Basis of Tet-On System --- p.15 / Chapter 1.7 --- The Basis of DNA Microarray --- p.18 / Chapter 1.8 --- The Basis of Two-Dimensional Electrophoresis --- p.20 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1 --- Construction of a Tet-On HBx Expressing Cell Model --- p.22 / Chapter 2.1.1 --- Cloning of HBx Gene into pTRE2 Vector --- p.22 / Chapter 2.1.1.1 --- PCR of HBx Gene --- p.22 / Chapter 2.1.1.2 --- Purification of the PCR Product --- p.23 / Chapter 2.1.1.3 --- Restriction Enzyme Digestion --- p.23 / Chapter 2.1.1.4 --- Ligation of HBx into pTRE Vector --- p.24 / Chapter 2.1.1.5 --- Transformation of the Ligation Product into Competent Cells --- p.24 / Chapter 2.1.2 --- Preparation of the Plasmid DNA --- p.24 / Chapter 2.1.2.1 --- DNA Sequencing of the Cloned Plasmid DNA --- p.25 / Chapter 2.1.3 --- Cell Culture of AML12 Cell Line --- p.26 / Chapter 2.1.4 --- Transfection of pTet-On Vector into AML12 Cells --- p.26 / Chapter 2.1.5 --- Selection of the Transfected AML12 Cells by G418 --- p.27 / Chapter 2.1.6 --- Single Clone Isolation --- p.27 / Chapter 2.1.6.1 --- Luciferase Assay for Selection of Highly Inducible Clones --- p.28 / Chapter 2.1.7 --- Second Transfection of pTRE-HBx Plasmid --- p.28 / Chapter 2.1.8 --- Selection of the Transfected Cells by Hygromycin --- p.29 / Chapter 2.1.9 --- Second Single Clone Isolation --- p.29 / Chapter 2.1.10 --- Total RNA Isolation --- p.29 / Chapter 2.1.11 --- DNase I Digestion --- p.30 / Chapter 2.1.12 --- First-Strand cDNA Synthesis --- p.31 / Chapter 2.1.13 --- RT-PCR of HBx Gene --- p.31 / Chapter 2.1.14 --- Northern Blotting --- p.32 / Chapter 2.1.15 --- Preparation of the Probe --- p.33 / Chapter 2.1.16 --- Northern Blot Hybridization --- p.33 / Chapter 2.1.17 --- 3H-Thymidine Incorporation Assay --- p.34 / Chapter 2.1.18 --- Analysis of Cell Cycle by Flow Cytometry --- p.35 / Chapter 2.2 --- Microarray Analysis of Differential Gene Expression upon HBx Induction --- p.35 / Chapter 2.2.1 --- Sample Preparation for Microarray Analysis --- p.35 / Chapter 2.2.2 --- Probe Labelling --- p.36 / Chapter 2.2.3 --- Microarray Hybridization --- p.37 / Chapter 2.2.4 --- RT-PCR of the Candidate Genes --- p.38 / Chapter 2.2.5 --- Northern Blot Analysis of the Candidate Genes --- p.39 / Chapter 2.3 --- Two-Dimensional (2D) Gel Electrophoretic Analysis --- p.40 / Chapter 2.3.1 --- Protein Sample Preparation for 2D Gel Electrophoresis --- p.40 / Chapter 2.3.2 --- First-Dimension Isoelectric Focusing (IEF) --- p.40 / Chapter 2.3.3 --- Second-Dimension SDS-PAGE --- p.41 / Chapter 2.3.4 --- Silver Stain of 2D Gel --- p.42 / Chapter 2.3.5 --- Mass Spectroscopic Analysis --- p.43 / Chapter 2.4 --- Subcellular Localization of HBx --- p.44 / Chapter 2.4.1 --- Cloning of HBx into Green Fluorescent Protein (GFP) Expression Vector --- p.44 / Chapter 2.4.2 --- Transfection of GFP-HBx --- p.44 / Chapter 2.4.3 --- Propidium Iodide (PI) Staining --- p.45 / Chapter 2.4.4 --- Mitochondria Staining --- p.45 / Chapter 2.4.5 --- Subcellular Localization Study using Epi-Fluorescent Microscopy --- p.45 / Chapter 2.5 --- Analysis of Mitochondrial Transmembrane Potential --- p.46 / Chapter Chapter 3 --- Results / Chapter 3.1 --- Construction of Tet-On AML12 Cell Line of HBx Gene --- p.47 / Chapter 3.2 --- Characterization of the HBx-Expressing Cell Model --- p.53 / Chapter 3.2.1 --- 3H-Thymidine Proliferation Assay --- p.53 / Chapter 3.2.2 --- Cell Cycle Analysis --- p.55 / Chapter 3.3 --- Microarray Analysis of Differential Gene Expression Pattern upon HBx Induction --- p.57 / Chapter 3.4 --- Northern Blot Analysis and RT-PCR of the Candidate Genes --- p.65 / Chapter 3.5 --- Differential Protein Expression Pattern under HBx Induction --- p.70 / Chapter 3.6 --- Subcellular Localization of HBx --- p.77 / Chapter 3.7 --- Analysis of Mitochondrial Transmembrane Potential --- p.83 / Chapter Chapter 4 --- Discussion / Chapter 4.1 --- Conditional HBx-Expressing Cell Model --- p.84 / Chapter 4.2 --- The Effects of HBx in Clone X18 --- p.86 / Chapter 4.2.1 --- Proliferative Effect of HBx --- p.86 / Chapter 4.2.2 --- Deregulation of G2/M Checkpoint by HBx --- p.86 / Chapter 4.3 --- Early Differential Gene Expression due to HBx Induction --- p.88 / Chapter 4.4 --- The Relationship of the Potential Candidate Genes and Cancer Development --- p.90 / Chapter 4.5 --- The Protein Expression Pattern due to HBx Induction --- p.93 / Chapter 4.6 --- The Subcellular Localization of HBx --- p.96 / Chapter 4.7 --- The Possible Involvement of HBx in Mitochondrial Transmembrane Potential --- p.98 / Chapter 4.8 --- Conclusions --- p.101 / Chapter 4.9 --- Future Prospects --- p.104 / Appendix --- p.107 / References --- p.112

Au Chi Chuen. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 157-169). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Table of Contents --- p.ii / Abstract --- p.v / 論文摘要 --- p.vii / Abbreviations --- p.viii / List of Figures --- p.ix / List of Tables --- p.x / Chapter Chapter 1 --- Introduction / Chapter 1.1 --- General introduction --- p.1 / Chapter 1.2 --- Hepatitis B virus and Hepatocellular carcinoma --- p.3 / Chapter 1.3 --- Pathogenesis of HBV related HCC --- p.6 / Chapter 1.4 --- Current screening test and tumor markers --- p.10 / Chapter 1.5 --- Expressed sequence tag (EST) sequencing --- p.13 / Chapter 1.6 --- Aim of the present study --- p.15 / Chapter 1.7 --- Characterization of KIAA0022 --- p.16 / Chapter Chapter 2 --- Materials and Methods / Chapter 2.1 --- Construction of liver HCC and normal counterpart libraries --- p.19 / Chapter 2.2 --- Plating out the human liver cDNA libraries --- p.19 / Chapter 2.3 --- PCR amplification of clones human liver cancer and the normal counterpart cDNA libraries --- p.21 / Chapter 2.4 --- Cycle sequencing of cloned human liver cancer and the normal counterpart cDNA libraries --- p.21 / Chapter 2.4.1 --- Dye-primer cycle sequencing (Pharmacia) --- p.21 / Chapter 2.4.1.1 --- Using Pharmacia LBKA.L.F. DNA sequencer --- p.21 / Chapter 2.4.1.2 --- Using Li-Cor 4200 Automated DNA sequencer --- p.22 / Chapter 2.4.2 --- Dye-terminator cycle sequencing (Pharmacia) --- p.22 / Chapter 2.5 --- Sequences analysis --- p.23 / Chapter 2.6 --- Cloning of full-length cDNA of KIAA0022 --- p.24 / Chapter 2.6.1 --- Amplification of KIAA0022 gene using PCR --- p.24 / Chapter 2.6.2 --- Purification of the PCR product --- p.25 / Chapter 2.6.3 --- Ligation --- p.25 / Chapter 2.6.4 --- One Shot® TOP 10 Chemical Transformation --- p.25 / Chapter 2.6.5 --- Small-scale preparation of the plasmid DNA --- p.26 / Chapter 2.6.6 --- Large-scale preparation of the plasmid DNA Table of Contents (continued) --- p.26 / Chapter 2.6.7 --- DNA sequencing of the full-length cDNA of KIAA0022 --- p.28 / Chapter 2.7 --- Northern Hybridization --- p.29 / Chapter 2.7.1 --- The Human multiple tissue Northern Blot --- p.29 / Chapter 2.7.2 --- Synthesis of the radiolabeled DNA probe --- p.29 / Chapter 2.7.3 --- Hybridization of the Northern blot --- p.30 / Chapter 2.8 --- Subcellular localization of KIAA0022 by tagging with green fluorescence protein (GFP) --- p.30 / Chapter 2.8.1 --- Amplification and purification of the KIAA0022 gene product --- p.30 / Chapter 2.8.2 --- Restriction enzymes digestion --- p.31 / Chapter 2.8.3 --- DNA ligation --- p.31 / Chapter 2.8.4 --- Preparation of the Escherichia coli competent cells for transformation --- p.31 / Chapter 2.8.5 --- Transformation of the plasmid DNA into competent Escherichia coli cells --- p.32 / Chapter 2.8.6 --- Small-scale preparation of the plasmid DNA --- p.32 / Chapter 2.8.7 --- Large-scale preparation of the plasmid DNA --- p.32 / Chapter 2.8.8 --- DNA sequencing of the cloned plasmid DNA --- p.33 / Chapter 2.8.9 --- Transfection --- p.33 / Chapter 2.8.10 --- Fluorescence microscopy examination --- p.33 / Chapter 2.9 --- Yeast two-hybrid screening assay --- p.34 / Chapter 2.9.1 --- "Cloning of the KIAA0022 gene into the yeast two-hybrid DNA-BD vector, pGBKT7" --- p.34 / Chapter 2.9.2 --- Small-scale transformation of pGBKT7-KIAA0022 plasmid --- p.34 / Chapter 2.9.2.1 --- Preparation of yeast competent cells --- p.34 / Chapter 2.9.2.2 --- Transformation of the pGBKT7-KIAA 0022 plasmid into the yeast strain PJ69-2A --- p.35 / Chapter 2.9.3 --- Screening a pretransformed library by yeast mating --- p.35 / Chapter 2.9.4 --- β -Galactosidase analysis - colony lift filter assay --- p.36 / Chapter 2.9.5 --- Analysis of yeast plasmid inserts using PCR and DNA sequencing --- p.37 / Chapter 2.9.5.1 --- PCR --- p.37 / Chapter 2.9.5.2 --- DNA sequencing --- p.37 / Chapter Chapter 3 --- Results / Chapter 3.1 --- Results of ESTs sequencing in normal counterpart and HCC libraries --- p.38 / Chapter 3.1.1 --- The sequencing results of the normal counterpart cDNA clones --- p.38 / Chapter 3.1.2 --- Sequencing results of the human liver cancer cDNA clones --- p.41 / Chapter 3.1.3 --- The accuracy of the automated sequencing technique --- p.41 / Chapter 3.1.4 --- Catalogue of normal counterpart ESTs --- p.45 / Chapter 3.1.5 --- Catalogue of liver cancer ESTs --- p.47 / Chapter 3.2 --- Identification of genes differentially expressed in HCC using in silico method --- p.115 / Chapter 3.3 --- Sequence analysis of KIAA0022 --- p.121 / Chapter 3.3.1 --- Structural analysis of KIAA0022 --- p.121 / Chapter 3.3.2 --- Homology alignment --- p.122 / Chapter 3.4 --- Tissue distribution and expression profile of KIAA0022 using Northern blot analysis --- p.132 / Chapter 3.5 --- Subcellular localization of the KIAA0022 tagging by green fluorescence protein --- p.134 / Chapter 3.6 --- Yeast two-hybrid screening assay --- p.136 / Chapter Chapter 4 --- Discussion / Chapter 4.1 --- Large-scale partial cDNA sequencing --- p.138 / Chapter 4.2 --- Characterization of ESTs --- p.139 / Chapter 4.3 --- Identification of genes differentially expressed in liver cancer using Poisson probability --- p.143 / Chapter 4.4 --- Characterization of KIAA0022 --- p.154 / Reference --- p.157 / Appendix --- p.170

Masayo Kotaka. / "May 1999." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (p. 179-190). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Hung Wah Johnson. / Thesis submitted in: August 2004. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 116-121). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgement --- p.iv / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Motivation --- p.1 / Chapter 1.2 --- Problem Statement --- p.3 / Chapter 1.3 --- Outline of the thesis --- p.6 / Chapter 2 --- Background --- p.8 / Chapter 2.1 --- Biological Background --- p.8 / Chapter 2.2 --- Sequence Alignments --- p.9 / Chapter 2.2.1 --- Pairwise Sequences Alignment --- p.11 / Chapter 2.2.2 --- Multiple Sequences Alignment --- p.15 / Chapter 2.3 --- Neighbor Joining Tree --- p.16 / Chapter 2.4 --- Marker Extractions --- p.18 / Chapter 2.5 --- Neural Network --- p.19 / Chapter 2.6 --- Conclusion --- p.22 / Chapter 3 --- Related Work --- p.23 / Chapter 3.1 --- FASTA --- p.23 / Chapter 3.2 --- Suffix Tree --- p.25 / Chapter 4 --- Sub-Sequence Segmentation Tree --- p.28 / Chapter 4.1 --- Introduction --- p.28 / Chapter 4.2 --- Problem Statement --- p.29 / Chapter 4.3 --- Design --- p.33 / Chapter 4.4 --- Time and space complexity analysis --- p.38 / Chapter 4.4.1 --- Performance Evaluation --- p.40 / Chapter 4.5 --- Summary --- p.48 / Chapter 5 --- Applications: Global Sequences Alignment --- p.51 / Chapter 5.1 --- Introduction --- p.51 / Chapter 5.2 --- Problem Statement --- p.53 / Chapter 5.3 --- Pairwise Alignment --- p.53 / Chapter 5.3.1 --- Algorithm --- p.53 / Chapter 5.3.2 --- Time and Space Complexity Analysis --- p.64 / Chapter 5.4 --- Multiple Sequences Alignment --- p.67 / Chapter 5.4.1 --- The Clustalw Algorithm --- p.68 / Chapter 5.4.2 --- MSA Using SSST --- p.70 / Chapter 5.4.3 --- Time and Space Complexity Analysis --- p.70 / Chapter 5.5 --- Experiments --- p.71 / Chapter 5.5.1 --- Experiment Setting --- p.72 / Chapter 5.5.2 --- Experimental Results --- p.72 / Chapter 5.6 --- Summary --- p.80 / Chapter 6 --- Applications: Marker Extractions --- p.81 / Chapter 6.1 --- Introduction --- p.81 / Chapter 6.2 --- Problem Statement --- p.82 / Chapter 6.3 --- The Multiple Sequence Alignment Approach --- p.85 / Chapter 6.3.1 --- Design --- p.85 / Chapter 6.4 --- Reference Sequence Alignment Approach --- p.88 / Chapter 6.4.1 --- Design --- p.90 / Chapter 6.5 --- Time and Space Complexity Analysis --- p.95 / Chapter 6.6 --- Experiments --- p.95 / Chapter 6.7 --- Summary --- p.99 / Chapter 7 --- HBV Application Framework --- p.101 / Chapter 7.1 --- Motivations --- p.101 / Chapter 7.2 --- The Procedure Flow of the Application --- p.102 / Chapter 7.2.1 --- Markers Extractions --- p.103 / Chapter 7.2.2 --- Rules Training and Prediction --- p.103 / Chapter 7.3 --- Results --- p.105 / Chapter 7.3.1 --- Clustering --- p.106 / Chapter 7.3.2 --- Classification --- p.107 / Chapter 7.4 --- Summary --- p.110 / Chapter 8 --- Conclusions --- p.112 / Chapter 8.1 --- Contributions --- p.112 / Chapter 8.2 --- Future Works --- p.114 / Chapter 8.2.1 --- HMM Learning --- p.114 / Chapter 8.2.2 --- Splice Sites Learning --- p.114 / Chapter 8.2.3 --- Faster Algorithm for Multiple Sequences Alignment --- p.115 / Bibliography --- p.121

Or Man Wai. / "January 2002." / "glued" in title is superscript. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.