noise management by molecular networks噪声管理的分子网络.pdfVIP

Noise Management by Molecular Networks 1,2,3 ¨ 4 5,6 Frank J. Bruggeman *, Nils Bluthgen , Hans V. Westerhoff 1 Regulatory Networks Group, Netherlands Institute for Systems Biology, Amsterdam, The Netherlands, 2 Life Sciences, Centre for Mathematics and Computer Science (CWI), Amsterdam, The Netherlands, 3 Integrative Bioinformatics, VU University, Amsterdam, The Netherlands, 4 Institute of Pathology and Institute of Theoretical Biology, ´ ¨ Charite Universitatsmedizin Berlin, Berlin, Germany, 5 Manchester Centre for Integrative Systems Biology, University of Manchester, Manchester, United Kingdom, 6 Molecular Cell Physiology, Netherlands Institute for Systems Biology, VU University, Amsterdam, The Netherlands Abstract Fluctuations in the copy number of key regulatory macromolecules (‘‘noise’’) may cause physiological heterogeneity in populations of (isogenic) cells. The kinetics of processes and their wiring in molecular networks can modulate this molecular noise. Here we present a theoretical framework to study the principles of noise management by the molecular networks in living cells. The theory makes use of the natural, hierarchical organization of those networks and makes their noise management more understandable in terms of network structure. Principles governing noise management by ultrasensitive systems, signaling cascades, gene networks and feedback circuitry are discovered using this approach. For a few frequently occurring network motifs we show how they manage noise. We derive simple and intuitive equations for noise in molecule copy numbers as a determinant of physiological heterogeneity. We show how noise levels and signal sensitivity can be set independently in molecular networks, but often changes in si