TY - JOUR T1 - Network organization of antibody interactions in sequence and structure space: the RADARS model JF - bioRxiv DO - 10.1101/438804 SP - 438804 AU - József Prechl Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/04/11/438804.abstract N2 - Adaptive immunity in vertebrates represents a complex self-organizing network of protein interactions that develops throughout the lifetime of an individual. While deep sequencing of the antibody repertoire may reveal clonal relationships, functional interpretation of such data is hampered by the inherent limitations of converting sequence to structure to function. In this paper a novel model of antibody interaction space and network, termed radial adjustment of system resolution, or RADARS, is proposed. The model is based on the radial growth of interaction affinity of antibodies towards an infinity of directions representing molecular shapes. Levels of interaction strength appear as shells of the spherical system. B-cell development and immune responses are interpreted in the model and quantitative properties of the antibody network are inferred from the physical properties of a quasi-spherical system growing multi-radially. The concept of system equilibrium constant is introduced, which is the median of equilibrium constants in the system and serves to define probability of interactions. The thermodynamic system is described by a power-law distribution of antibody free energies with a network degree exponent of phi square, representing a scale-free network of antibody interactions.Thus, the RADARS model implies that an absolute sequence space is reduced to a thermodynamically viable structure space by means of a network of interactions, which control B-cell development. Understanding such quantitative network properties of the system should help the organization of sequence-derived structural data, offering the possibility to relate sequence to function in a complex, self-organizing biological system. ER -