Browsing by Author "Livesey, Michelle Chantel"
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Item Discovering cancer subtypes by tracking cancer progression with transcriptomic data through the multi-stage process of cancer development.(University of the Western Cape, 2023) Livesey, Michelle Chantel; Bendou, HocineBackground: The development of cancer is driven by genomic alterations, which become more heterogeneous as the disease progresses throughout the stages. Consequently, cancer patients have differential levels of sensitivity to treatment. Tumor heterogeneity thus contributes to therapeutic failure, which ultimately leads to the generally poor prognosis and poor overall survival outcome associated with cancer. Introduction: Transcriptomic profiles can be used to track cancer progression based on gene expression changes that occur throughout the multi-stage process of cancer development. The accumulated genetic changes can be detected when gene expression levels in advanced-stage are less variable but show high variability in early-stage. Normalizing advanced-stage expression samples with early-stage and clustering of the normalized expression samples can reveal cancers with unique gene expression patterns based on cancer progression. Aims: A computational method was employed to investigate cancer progression through RNASeq expression profiles across the multi-stage process of cancer development. The method was assessed in a subtype of the heterogeneous kidney cancer and enabled the discovery of in-depth cancer subtypes based on the differences in gene expression profiles. Methods: A preliminary study was performed by downloading RNA-sequenced gene expression and associated phenotypic and survival profiles of Diffuse Large B-cell Lymphoma, Lung cancer, Liver cancer, Cervical cancer, and Testicular cancer from the UCSC Xena database. Similarly, Kidney renal clear cell carcinoma (KIRC) was downloaded as a validation dataset. Advanced-stage samples were normalized with early-stage to consider heterogeneity differences in the multi-stage cancer progression. The normalized gene expression of the preliminary cancer datasets was subjected to weighted gene co-expression network analysis. Gene modules were linked to cancer-related proteins and pathways using enrichment analyses.Item Genetic landscape of the mitochondrial DNA control region in South African populations(ScienceDirect, 2019) Livesey, Michelle ChantelA high-quality dataset of the mitochondrial DNA control region sequences was generated with Sanger and next-generation sequencing. The study was aimed at characterizing the maternal genetic ancestry and analyzing the haplogroup distribution of 246 individuals residing in South Africa. The study presents mtDNA sequences in South Africa for forensic applications.Item The geographical analysis of the mitochondrial DNA control region found in southern African population's by using a bioinformatics approach(University of the Western Cape, 2020) Livesey, Michelle Chantel; D'Amato, Maria EugeniaSouth Africa’s demographic complexity has been historically shaped by interethnic admixture between the native KhoiSan inhabitants and the Bantu expansion that started 3000 - 5000 YBP and reached South Africa about 1000 years ago. This, followed by the arrival of the European settlers in the 16th century who brought in slaves from their Asian colonies, mainly from Malaysia and the east- and western Africa. By the late 19th- and early 20th century colonial India (South Asia) also migrated to South Africa. It has been hypothesized that the history of South African has influence ethnic group distribution in South African, to the degree that it is not homogeneous. This study further theorized that the history contributed to the gene flow at a regional level and not restricted to the ethnic distribution of genetic variation. Therefore, this study focuses on the geographical and ethnic dispersal of maternal lineages by investigating the mitochondrial DNA (mtDNA). It is predicted that the maternal lineages could be limited or appear in high frequencies in specific ethnic and/or geographical region in South Africa. This, in turn, can aid mitochondrial DNA forensic human identification applications when a specific haplotype is questioned. This study produced a complete mitochondrial DNA control region (nucleotide position 16 024-576) sequences generated with Sanger and next-generation sequencing for 246 individuals residing in the Western Cape, Northern Cape and KwaZulu-Natal provinces of South Africa. The control region is of particular interest due to the vast majority of rapidly evolving sites that are of relevance in both forensic genetics and population studies. The haplotypes were inferred against the revised Cambridge Reference Sequences and haplogroups were determined by online tool HaploGrep 2.