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

An experiment-oriented integrated model of the regulation of the biological ly ubiquitous NF-kappa B 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) implement ed a deep biological ontology including molecular, ultrastructural, cytolog ical, histological, and organismic definitions. KB states, relationships, p redicates, and heuristics also represented process interactions between rea ctive oxygen species, growth factors, and a variety of kinases phosphorylat ing intermediate molecules in the NF-kappa B and AP-1 regulatory signaling pathways. The system successfully simulated the molecular process steps und erlying outcomes of eight different molecular generics laboratory experimen ts, including those dealing with NF-kappa B and AP-1 regulation in immunode ficiency virus infection and tumor necrosis factor responses. (C) 1999 Else vier Science B.V. All rights reserved.