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The ultimate proof of our understanding of natural or technological systems is reflected in our ability to control them. Although control theory offers mathematical tools for steering engineered and natural systems towards a desired state, a framework to control complex self-organized systems is lacking. Here we develop analytical tools to study the(More)
A quantitative description of a complex system is inherently limited by our ability to estimate the system's internal state from experimentally accessible outputs. Although the simultaneous measurement of all internal variables, like all metabolite concentrations in a cell, offers a complete description of a system's state, in practice experimental access(More)
We introduce the concept of control centrality to quantify the ability of a single node to control a directed weighted network. We calculate the distribution of control centrality for several real networks and find that it is mainly determined by the network's degree distribution. We show that in a directed network without loops the control centrality of a(More)
Our ability to control complex systems is a fundamental challenge of contemporary science. Recently introduced tools to identify the driver nodes, nodes through which we can achieve full control, predict the existence of multiple control configurations, prompting us to classify each node in a network based on their role in control. Accordingly a node is(More)
Controlling large natural and technological networks is an outstanding challenge. It is typically neither feasible nor necessary to control the entire network, prompting us to explore target control: the efficient control of a preselected subset of nodes. We show that the structural controllability approach used for full control overestimates the minimum(More)
How disease-associated mutations impair protein activities in the context of biological networks remains mostly undetermined. Although a few renowned alleles are well characterized, functional information is missing for over 100,000 disease-associated variants. Here we functionally profile several thousand missense mutations across a spectrum of Mendelian(More)
Motivation Patient stratification or disease subtyping is crucial for precision medicine and personalized treatment of complex diseases. The increasing availability of high-throughput molecular data provides a great opportunity for patient stratification. Many clustering methods have been employed to tackle this problem in a purely data-driven manner. Yet,(More)
Recent studies have made important advances in identifying sensor or driver nodes, through which we can observe or control a complex system. But the observational uncertainty induced bymeasurement noise and the energy required for control continue to be significant challenges in practical applications. Here we show that the variability of control energy and(More)
Controlling complex networked systems to desired states is a key research goal in contemporary science. Despite recent advances in studying the impact of network topology on controllability, a comprehensive understanding of the synergistic effect of network topology and individual dynamics on controllability is still lacking. Here we offer a theoretical(More)
Microbiome-based stratification of healthy individuals into compositional categories, referred to as "enterotypes" or "community types", holds promise for drastically improving personalized medicine. Despite this potential, the existence of community types and the degree of their distinctness have been highly debated. Here we adopted a dynamic systems(More)