computational immunology meets bioinformatics the use of prediction tools for molecular binding in the simulation of the immune system计算免疫学与分子生物信息学预测工具的使用绑定的模拟免疫系统.pdfVIP

Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System 1 2 3 3 Nicolas Rapin , Ole Lund , Massimo Bernaschi , Filippo Castiglione * 1 Biotech Research and Innovation Centre and Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark, 2 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark, 3 Institute for Computing Applications, National Research Council, Rome, Italy Abstract We present a new approach to the study of the immune system that combines techniques of systems biology with information provided by data-driven prediction methods. To this end, we have extended an agent-based simulator of the immune response, C-IMMSIM, such that it represents pathogens, as well as lymphocytes receptors, by means of their amino acid sequences and makes use of bioinformatics methods for T and B cell epitope prediction. This is a key step for the simulation of the immune response, because it determines immunogenicity. The binding of the epitope, which is the immunogenic part of an invading pathogen, together with activation and cooperation from T helper cells, is required to trigger an immune response in the affected host. To determine a pathogen’s epitopes, we use existing prediction methods. In addition, we propose a novel method, which uses Miyazawa and Jernigan protein–protein potential measurements, for assessing molecular binding in the context of immune complexes. We benchmark the resulting model by simulating a classical immunization experiment that repro