Saudi Cultural Missions Theses & Dissertations
Permanent URI for this communityhttps://drepo.sdl.edu.sa/handle/20.500.14154/10
Browse
3 results
Search Results
Item Restricted The Impact Of Dilated Cardiomyopathy on Cell-Type Diversity and Gene Expression(The University of Manchester, 2024) Alammari, Eman; Eales, James; Eales, JamesBackground: Dilated cardiomyopathy (DCM) is a leading cause of heart failure characterised by enlarged ventricles and reduced cardiac function. Despite advancements, understanding the cellular and molecular processes related to DCM remains challenging. Objectives: This study uses single-cell transcriptomics to identify unique gene expression patterns and cellular diversity in DCM to improve patient stratification and clinical care. Methods: Publicly available single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) data from normal cardiac tissues and DCM patients were obtained from the GEO dataset GSE183852. The analysis included 269,794 samples from 45 participants, comprising 36,488 DCM cells, 66,669 DCM nuclei, 12,554 healthy cells, and 154,083 healthy nuclei. Data analysis involved quality control, normalisation, data integration, dimensionality reduction, clustering, DE analysis, and Gene set enrichment analysis (GSEA). Results: Principal component analysis identified 50 principal components. Unsupervised cluster annotation revealed 21 cell types in nuclei samples and 15 in cell samples. The analysis showed an underrepresentation of cardiomyocytes in the scRNA samples. Cell composition analysis demonstrated significant differences in cell type abundance between DCM and healthy tissues, including an increased ratio of fibroblasts in DCM and a decrease in cardiomyocytes. DE analysis identified several significant differentially expressed genes (DEGs), MYH6. DEGs were shown to overlap with well-known DCM genes from the PannelApp list. GSEA validated the enrichment of our genes in DCM-associated pathways; moreover, a strong trend of downregulation of many critical pathways was found across many cell types, including metabolic and energy pathways. Conclusion: Despite some limitations of single-cell technology in preserving certain cardiac cell types, the analysis revealed significant differences in cell type abundance and DE profile between healthy and DCM samples. This discovery of distinct gene expression patterns in DCM samples compared to healthy individuals presents potential diagnostic and therapeutic targets, offering hope for improved patient outcomes.6 0Item Restricted Computational Analysis of Antibody Binding Mechanisms to the Omicron RBD of SARS-CoV-2 Spike Protein: Identification of Epitopes and Hotspots for De opes and Hotspots for Developing E eloping Effective Therapeutic apeutic Strategies.(2023-05) Alshahrani, Mohammed Rajeh; Verkhivker, GennadyThe advent of the Omicron strain of SARS-CoV-2 has elicited apprehension regarding its potential influence on the effectiveness of current vaccines and antibody treatments. The present investigation involved the implementation of mutational scanning analyses to examine the impact of Omicron mutations on the binding affinity of four categories of antibodies that target the Omicron receptor binding domain (RBD) of the Spike protein. The study demonstrates that the Omicron variant harbors 23 unique mutations across the RBD regions I, II, III, and IV. Of these mutations, seven are shared between RBD regions I and II, while three are shared among RBD regions I, II, and III. The findings suggest that the mutations exert a noteworthy influence on the antibodies' binding affinity, especially in Class II and Class III antibodies. Among the mutations, those located at positions R346, L452, and F490 appear to have a particularly notable impact. Multiple mutations were detected at positions F375, Y501, and H505 across all sub-variants of Omicron, indicating their potential significance in evading the immune system. The mutations could potentially bear significant ramifications with regards to immune evasion. The research underscores the significance of continuous observation and scrutiny of viral mutations in order to guide the creation of efficacious treatments for novel strains of SARS-CoV-2.12 0Item Restricted Computational Prediction of pH-Dependent Binding Energies in HPV Capsid Antibody Interactions(ProQuest, 2023-04-13) Alqarni, Amjad Mahdi; Joshua L. PhillipsHPV is the most common sexually transmitted infection in the world. In high-risk types, HPV infection is associated with virtually all cervical cancers and a significant proportion of anogenital and oropharyngeal cancers. Neutralizing antibodies can prevent HPV infection with their effectiveness depending on the way they interact with HPV capsid proteins. The ability of antibodies to attach to capsid proteins is influenced by pH variations, which can impact the characteristics and stability of both the viral capsid and the antibody. In this thesis, we apply a computational simulation pipeline to predict the pH- dependent binding energies in HPV capsid-antibody interactions. Our results predict that there is a strong preference for binding to antibody 28F10 for HPV subtypes 6, 16, 18, 33, and 58 while A12A3 shows a strong preference for HPV 35 and 59. The results also predict that both antibodies bind non-preferentially to the HPV 11 capsid.26 0