Multi-layered model of individual HIV infection progression and mechanisms of phenotypical expression
Year: 2008
Type: dissertation
Abstract: Development of a computational model is reported, which focuses on aspects of individuality in biological phenomena.Of particular interest are factors related to the immune response to HIV infection and how these interact within a complex system leading to significant variations in latency period.A multi-layered approach is chosen, with the most crucial layer comprising a large-scale agent-based model lymph network.Agent-cell reciprocity permits isolation of key features, e.g.cell mobility, viral mutation.Cell mobility, in particular, is incorporated in an innovative way, due to parallel implementation which permits realistic size of the lymph network.This implementation, using lymph nodes as key structural units, also permits inclusion of localised effects, e.g.early infection in the gastro-intestinal tract, which is increasingly reported as having a decisive impact on longterm disease progression.Additional layers of the model provide a foundation for investigation into the phenotypicallevel mechanisms of the immune response implemented in the main layer.The objective here is to gain insight on how these mechanisms originate from a sub-layer of interactions, (both genetic and epigenetic).Gene interactions are commonly studied through microarray techniques and generate highly complex dependencies.A validation framework for such analysis is proposed, and a model of infection-induced epigenetic changes, (within the agent-based paradigm), is developed.
Author: Dimitri Perrin
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W164455894