A qualitative process system for modeling NF-kappaB and AP-1 gene regulation in immune cell biology research.

Abstract

An experiment-oriented integrated model of the regulation of the biologically ubiquitous NF-kappaB and AP-1 gene transcription promoters was built by extending a previously developed qualitative process system for simulating cell behavior in the immune system. The core knowledge base (KB) implemented a deep biological ontology including molecular, ultrastructural, cytological, histological, and organismic definitions. KB states, relationships, predicates, and heuristics also represented process interactions between reactive oxygen species, growth factors, and a variety of kinases phosphorylating intermediate molecules in the NF-kappaB and AP-1 regulatory signaling pathways. The system successfully simulated the molecular process steps underlying outcomes of eight different molecular genetics laboratory experiments, including those dealing with NF-kappaB and AP-1 regulation in immunodeficiency virus infection and tumor necrosis factor responses.