Efficient Bayesian Learning in Social Networks with Gaussian Estimators

We consider a group of Bayesian agents who try to estimate a state of the world $\theta$ through interaction on a social network. Each agent $v$ initially receives a private measurement of $\theta$: a number $S_v$ picked from a Gaussian distribution with mean $\theta$ and standard deviation one. Then, in each discrete time iteration, each reveals its estimate of $\theta$ to its neighbors, and, observing its neighbors' actions, updates its belief using Bayes' Law. This process aggregates information efficiently, in the sense that all the agents converge to the belief that they would have, had they access to all the private measurements. We show that this process is computationally efficient, so that each agent's calculation can be easily carried out. We also show that on any graph the process converges after at most $2N \cdot D$ steps, where $N$ is the number of agents and $D$ is the diameter of the network. Finally, we show that on trees and on distance transitive-graphs the process converges after $D$ steps, and that it preserves privacy, so that agents learn very little about the private signal of most other agents, despite the efficient aggregation of information. Our results extend those in an unpublished manuscript of the first and last authors.Comment: Added coauthor. Added proofs for fast convergence on trees and distance transitive graphs. Also, now analyzing a notion of privac

Allosteric proteins as logarithmic sensors

Many sensory systems, from vision and hearing in animals to signal transduction in cells, respond to fold changes in signal relative to background. Responding to fold change requires that the system senses signal on a logarithmic scale, responding identically to a change in signal level from 1 to 3, or from 10 to 30. It is an ongoing search in the field to understand the ways in which a logarithmic sensor can be implemented at the molecular level. In this work, we present evidence that logarithmic sensing can be implemented with a single protein, by means of allosteric regulation. Specifically, we find that mathematical models show that allosteric proteins can respond to stimuli on a logarithmic scale. Next, we present evidence from measurements in the literature that some allosteric proteins do operate in a parameter regime that permits logarithmic sensing. Finally, we present examples suggesting that allosteric proteins are indeed used in this capacity: allosteric proteins play a prominent role in systems where fold-change detection has been proposed. This finding suggests a role as logarithmic sensors for the many allosteric proteins across diverse biological processes

Architecture, Design, and Tradeoffs in Biomolecular Feedback Systems

A core pursuit in systems and synthetic biology is the analysis of the connection between the low-level structure and parameters of a biomolecular network and its high-level function and performance. Elucidating this mapping has become increasingly feasible as precise measurements of both input parameters and output dynamics become abundant. At the same time, cross-pollination between biology and engineering has led to the realization that many of the mathematical tools from control theory are well-suited to analyze biological processes. The goal of this thesis is to use tools from control theory to analyze a variety of biomolecular systems from both natural and synthetic settings, and subsequently yield insight into the architecture, tradeoffs, and limitations of biological network. In Chapter 2, I demonstrate how allosteric proteins can be used to respond logarithmically to changes in signal. In Chapter 3, I show how control theoretic techniques can be used to inform the design of synthetic integral feedback networks that implement feedback with a sequestration mechanism. Finally, in Chapter 4 I present a novel simplified model of the E. coli heat shock response system and show how the the mapping of circuit parameters to function depends on the network's architecture. The unifying theme of this research is that the conceptual framework used to study engineered systems is remarkably well-suited to biology. That being said, it is important to apply these tools in a way that is informed by the molecular details of biological processes. By combining structural and biochemical data with the functional perspective of engineering, it is possible to understand the architectural principles that underlie living systems.</p

Allosteric proteins as logarithmic sensors

Many sensory systems, from vision and hearing in animals to signal transduction in cells, respond to fold changes in signal relative to background. Responding to fold change requires that the system senses signal on a logarithmic scale, responding identically to a change in signal level from 1 to 3, or from 10 to 30. It is an ongoing search in the field to understand the ways in which a logarithmic sensor can be implemented at the molecular level. In this work, we present evidence that logarithmic sensing can be implemented with a single protein, by means of allosteric regulation. Specifically, we find that mathematical models show that allosteric proteins can respond to stimuli on a logarithmic scale. Next, we present evidence from measurements in the literature that some allosteric proteins do operate in a parameter regime that permits logarithmic sensing. Finally, we present examples suggesting that allosteric proteins are indeed used in this capacity: allosteric proteins play a prominent role in systems where fold-change detection has been proposed. This finding suggests a role as logarithmic sensors for the many allosteric proteins across diverse biological processes

Design Guidelines For Sequestration Feedback Networks

Integral control is commonly used in mechanical and electrical systems to ensure perfect adaptation. A proposed design of integral control for synthetic biological systems employs the sequestration of two biochemical controller species. The unbound amount of controller species captures the integral of the error between the current and the desired state of the system. However, implementing integral control inside bacterial cells using sequestration feedback has been challenging due to the controller molecules being degraded and diluted. Furthermore, integral control can only be achieved under stability conditions that not all sequestration feedback networks fulfill. In this work, we give guidelines for ensuring stability and good performance (small steady-state error) in sequestration feedback networks. Our guidelines provide simple tuning options to obtain a flexible and practical biological implementation of sequestration feedback control. Using tools and metrics from control theory, we pave the path for the systematic design of synthetic biological systems

Architectural Principles for Characterizing the Performance of Antithetic Integral Feedback Networks

As we begin to design increasingly complex synthetic biomolecular systems, it is essential to develop rational design methodologies that yield predictable circuit performance. Here we apply theoretical tools from the theory of control and dynamical systems to yield practical insights into the architecture and function of a particular class of biological feedback circuit. Specifically, we show that it is possible to analytically characterize both the operating regime and performance tradeoffs of a sequestration feedback circuit architecture. Further, we demonstrate how these principles can be applied to inform the design process of a particular synthetic feedback circuit

Experimental and Computational Analysis of a Large Protein Network That Controls Fat Storage Reveals the Design Principles of a Signaling Network

An approach combining genetic, proteomic, computational, and physiological analysis was used to define a protein network that regulates fat storage in budding yeast (Saccharomyces cerevisiae). A computational analysis of this network shows that it is not scale-free, and is best approximated by the Watts-Strogatz model, which generates “small-world” networks with high clustering and short path lengths. The network is also modular, containing energy level sensing proteins that connect to four output processes: autophagy, fatty acid synthesis, mRNA processing, and MAP kinase signaling. The importance of each protein to network function is dependent on its Katz centrality score, which is related both to the protein’s position within a module and to the module’s relationship to the network as a whole. The network is also divisible into subnetworks that span modular boundaries and regulate different aspects of fat metabolism. We used a combination of genetics and pharmacology to simultaneously block output from multiple network nodes. The phenotypic results of this blockage define patterns of communication among distant network nodes, and these patterns are consistent with the Watts-Strogatz model