This thesis is dedicated to applications of high-throughput sequencing data analysis in immunology. Initially, the project included the part focusing on the T cell biology in the context of cancer, supervised by Dr. Pia Kvistborg, and the part focusing on the translational analys
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This thesis is dedicated to applications of high-throughput sequencing data analysis in immunology. Initially, the project included the part focusing on the T cell biology in the context of cancer, supervised by Dr. Pia Kvistborg, and the part focusing on the translational analysis of the breast cancer clinical trials, supervised by Dr. Marleen Kok, both under the general supervision of Dr. Lodewyk Wessels. Because of the COVID19 pandemic, Part 1 of this work focused instead on the T cell functionality in the context of COVID-19. As Dr. Kvistborg resigned in 2022, the larger part of the thesis, Part 2, was completed under the supervision of Dr. Kok and Dr. Wessels, the copromotor and promotor of this work. Thus, this thesis describes bioinformatics approaches to the translational studies in immunology in the context of COVID-19 disease and breast cancer. We demonstrate that the use of genomic and transcriptomic data, including whole-exome and shallow whole-genome DNA sequencing and single-cell and bulk RNA sequencing, allows us to make conclusions about the underlying biology of the disease and identify biomarkers related to disease outcomes and response to treatment. Fatigue damage has been observed in offshore pre-piling templates, yet current design checks do not fully account for it. This thesis examines one potential mechanism: the interaction between the pile, the surrounding water confined in the sleeve annulus, and the template during installation. To capture this behaviour, a high-order cylindrical shell model with soil impedances is combined with a confined-water added-mass representation. The dynamic response under hammer impacts is then solved using modal superposition. Parametric studies are carried out on industry-scale geometries to assess the effects of pile embedment depth, sleeve length, and annular gap size. Transient annular pressures are then converted into fatigue metrics using rainflow counting. A key finding of this study is that confinement is the decisive factor. By increasing the effective hydrodynamic inertia, confinement lowers the natural frequencies of the system. As a result, radially dominated modes are shifted into the frequency range excited by the hammer. This causes originally separate resonances to merge into a dense modal cluster, which amplifies the pressure response. The mode shapes in this cluster are less effective at mobilising soil damping because they contain many local oscillations. As a result, the motions are damped less efficiently, leading to oscillations that are both stronger and more persistent. Compared with unconfined water, where annular pressures are small and cycles are not fatigue-critical, confined cases generate MPa-level pressures and raise the Miner’s sum by up to four orders of magnitude. Severity increases with smaller gaps and longer sleeves. It diminishes with greater embedment due to added stiffness and damping, although this comes with an increase in the number of cycles. While viscosity, compressibility and full soil nonlinearity are idealised, the framework isolates the confinement-driven inertial mechanism and identifies clear design levers. This study clarifies governing parameters and coupling pathways, offering a baseline for future measurements and high-fidelity modelling, but it is not intended as a predictive design tool.