A qualitative process system for modeling NF-kappaB and AP-1 gene regulation in immune cell biology research.
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.
Trelease
R B
RB
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA. trelease@ucla.edu
Henderson
R A
RA
Park
J B
JB
D000917:Antibody Formation / Q000235:genetics; D001185:Artificial Intelligence; D003198:Computer Simulation; D003199:Computer Systems; D005786:Gene Expression Regulation / Q000235:genetics*; D006133:Growth Substances; D007111:Immunity, Cellular / Q000235:genetics*; D008838:Microcomputers; D008957:Models, Genetic; D016328:NF-kappa B / Q000235:genetics*; D010764:Phosphorylase Kinase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000235:genetics*
D006133:Growth Substances; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D010764:Phosphorylase Kinase