Prediction of protein continuum secondary structure with probabilistic models based on NMR solved structures

Background: The structure of proteins may change as a result of the inherent flexibility of some protein regions. We develop and explore probabilistic machine learning methods for predicting a continuum secondary structure, i.e. assigning probabilities to the conformational states of a residue. We train our methods using data derived from high-quality NMR models. Results: Several probabilistic models not only successfully estimate the continuum secondary structure, but also provide a categorical output on par with models directly trained on categorical data. Importantly, models trained on the continuum secondary structure are also better than their categorical counterparts at identifying the conformational state for structurally ambivalent residues. Conclusion: Cascaded probabilistic neural networks trained on the continuum secondary structure exhibit better accuracy in structurally ambivalent regions of proteins, while sustaining an overall classification accuracy on par with standard, categorical prediction methods.

The interplay between microscopic and mesoscopic structures in complex networks

Understanding a complex network's structure holds the key to understanding its function. The physics community has contributed a multitude of methods and analyses to this cross-disciplinary endeavor. Structural features exist on both the microscopic level, resulting from differences between single node properties, and the mesoscopic level resulting from properties shared by groups of nodes. Disentangling the determinants of network structure on these different scales has remained a major, and so far unsolved, challenge. Here we show how multiscale generative probabilistic exponential random graph models combined with efficient, distributive message-passing inference techniques can be used to achieve this separation of scales, leading to improved detection accuracy of latent classes as demonstrated on benchmark problems. It sheds new light on the statistical significance of motif-distributions in neural networks and improves the link-prediction accuracy as exemplified for gene-disease associations in the highly consequential Online Mendelian Inheritance in Man database. © 2011 Reichardt et al.

Predicting and diagnosing faults in wastewater treatment process by Bayesian Belief Networks

Diagnosing faults in wastewater treatment, like diagnosis of most problems, requires bi-directional plausible reasoning. This means that both predictive (from causes to symptoms) and diagnostic (from symptoms to causes) inferences have to be made, depending on the evidence available, in reasoning for the final diagnosis. The use of computer technology for the purpose of diagnosing faults in the wastewater process has been explored, and a rule-based expert system was initiated. It was found that such an approach has serious limitations in its ability to reason bi-directionally, which makes it unsuitable for diagnosing tasks under the conditions of uncertainty. The probabilistic approach known as Bayesian Belief Networks (BBNS) was then critically reviewed, and was found to be well-suited for diagnosis under uncertainty. The theory and application of BBNs are outlined. A full-scale BBN for the diagnosis of faults in a wastewater treatment plant based on the activated sludge system has been developed in this research. Results from the BBN show good agreement with the predictions of wastewater experts. It can be concluded that the BBNs are far superior to rule-based systems based on certainty factors in their ability to diagnose faults and predict systems in complex operating systems having inherently uncertain behaviour.

Dynamic decision networks for decision-making in self-adaptive systems:a case study

Bayesian decision theory is increasingly applied to support decision-making processes under environmental variability and uncertainty. Researchers from application areas like psychology and biomedicine have applied these techniques successfully. However, in the area of software engineering and speci?cally in the area of self-adaptive systems (SASs), little progress has been made in the application of Bayesian decision theory. We believe that techniques based on Bayesian Networks (BNs) are useful for systems that dynamically adapt themselves at runtime to a changing environment, which is usually uncertain. In this paper, we discuss the case for the use of BNs, speci?cally Dynamic Decision Networks (DDNs), to support the decision-making of self-adaptive systems. We present how such a probabilistic model can be used to support the decision making in SASs and justify its applicability. We have applied our DDN-based approach to the case of an adaptive remote data mirroring system. We discuss results, implications and potential bene?ts of the DDN to enhance the development and operation of self-adaptive systems, by providing mechanisms to cope with uncertainty and automatically make the best decision.

Probabilistic synchronisation of pinning control

This paper is concerned with synchronization of complex stochastic dynamical networks in the presence of noise and functional uncertainty. A probabilistic control method for adaptive synchronization is presented. All required probabilistic models of the network are assumed to be unknown therefore estimated to be dependent on the connectivity strength, the state and control values. Robustness of the probabilistic controller is proved via the Liapunov method. Furthermore, based on the residual error of the network states we introduce the definition of stochastic pinning controllability. A coupled map lattice with spatiotemporal chaos is taken as an example to illustrate all theoretical developments. The theoretical derivation is complemented by its validation on two representative examples.

Fully probabilistic control for stochastic nonlinear control systems with input dependent noise

Robust controllers for nonlinear stochastic systems with functional uncertainties can be consistently designed using probabilistic control methods. In this paper a generalised probabilistic controller design for the minimisation of the Kullback-Leibler divergence between the actual joint probability density function (pdf) of the closed loop control system, and an ideal joint pdf is presented emphasising how the uncertainty can be systematically incorporated in the absence of reliable systems models. To achieve this objective all probabilistic models of the system are estimated from process data using mixture density networks (MDNs) where all the parameters of the estimated pdfs are taken to be state and control input dependent. Based on this dependency of the density parameters on the input values, explicit formulations to the construction of optimal generalised probabilistic controllers are obtained through the techniques of dynamic programming and adaptive critic methods. Using the proposed generalised probabilistic controller, the conditional joint pdfs can be made to follow the ideal ones. A simulation example is used to demonstrate the implementation of the algorithm and encouraging results are obtained.

Probabilistic control for uncertain systems

In this paper a new framework has been applied to the design of controllers which encompasses nonlinearity, hysteresis and arbitrary density functions of forward models and inverse controllers. Using mixture density networks, the probabilistic models of both the forward and inverse dynamics are estimated such that they are dependent on the state and the control input. The optimal control strategy is then derived which minimizes uncertainty of the closed loop system. In the absence of reliable plant models, the proposed control algorithm incorporates uncertainties in model parameters, observations, and latent processes. The local stability of the closed loop system has been established. The efficacy of the control algorithm is demonstrated on two nonlinear stochastic control examples with additive and multiplicative noise.

Fully probabilistic control design in an adaptive critic framework

Optimal stochastic controller pushes the closed-loop behavior as close as possible to the desired one. The fully probabilistic design (FPD) uses probabilistic description of the desired closed loop and minimizes Kullback-Leibler divergence of the closed-loop description to the desired one. Practical exploitation of the fully probabilistic design control theory continues to be hindered by the computational complexities involved in numerically solving the associated stochastic dynamic programming problem. In particular very hard multivariate integration and an approximate interpolation of the involved multivariate functions. This paper proposes a new fully probabilistic contro algorithm that uses the adaptive critic methods to circumvent the need for explicitly evaluating the optimal value function, thereby dramatically reducing computational requirements. This is a main contribution of this short paper.

Probabilistic DHP adaptive critic for nonlinear stochastic control systems

Following the recently developed algorithms for fully probabilistic control design for general dynamic stochastic systems (Herzallah & Káarnáy, 2011; Kárný, 1996), this paper presents the solution to the probabilistic dual heuristic programming (DHP) adaptive critic method (Herzallah & Káarnáy, 2011) and randomized control algorithm for stochastic nonlinear dynamical systems. The purpose of the randomized control input design is to make the joint probability density function of the closed loop system as close as possible to a predetermined ideal joint probability density function. This paper completes the previous work (Herzallah & Kárnáy, 2011; Kárný, 1996) by formulating and solving the fully probabilistic control design problem on the more general case of nonlinear stochastic discrete time systems. A simulated example is used to demonstrate the use of the algorithm and encouraging results have been obtained.

Generalised Riccati solution and pinning control of complex stochastic networks

This paper considers the global synchronisation of a stochastic version of coupled map lattices networks through an innovative stochastic adaptive linear quadratic pinning control methodology. In a stochastic network, each state receives only noisy measurement of its neighbours' states. For such networks we derive a generalised Riccati solution that quantifies and incorporates uncertainty of the forward dynamics and inverse controller in the derivation of the stochastic optimal control law. The generalised Riccati solution is derived using the Lyapunov approach. A probabilistic approximation type algorithm is employed to estimate the conditional distributions of the state and inverse controller from historical data and quantifying model uncertainties. The theoretical derivation is complemented by its validation on a set of representative examples.

Scalable harmonization of complex networks with local controllers

Computational and communication complexities call for distributed, robust, and adaptive control. This paper proposes a promising way of bottom-up design of distributed control in which simple controllers are responsible for individual nodes. The overall behavior of the network can be achieved by interconnecting such controlled loops in cascade control for example and by enabling the individual nodes to share information about data with their neighbors without aiming at unattainable global solution. The problem is addressed by employing a fully probabilistic design, which can cope with inherent uncertainties, that can be implemented adaptively and which provide a systematic rich way to information sharing. This paper elaborates the overall solution, applies it to linear-Gaussian case, and provides simulation results.

Towards probabilistic synchronization of local controllers

The traditional use of global and centralised control methods, fails for large, complex, noisy and highly connected systems, which typify many real world industrial and commercial systems. This paper provides an efficient bottom up design of distributed control in which many simple components communicate and cooperate to achieve a joint system goal. Each component acts individually so as to maximise personal utility whilst obtaining probabilistic information on the global system merely through local message-passing. This leads to an implied scalable and collective control strategy for complex dynamical systems, without the problems of global centralised control. Robustness is addressed by employing a fully probabilistic design, which can cope with inherent uncertainties, can be implemented adaptively and opens a systematic rich way to information sharing. This paper opens the foreseen direction and inspects the proposed design on a linearised version of coupled map lattice with spatiotemporal chaos. A version close to linear quadratic design gives an initial insight into possible behaviours of such networks.

Trust based security mechanisms for wireless sensor networks

Wireless sensor networks are emerging as effective tools in the gathering and dissemination of data. They can be applied in many fields including health, environmental monitoring, home automation and the military. Like all other computing systems it is necessary to include security features, so that security sensitive data traversing the network is protected. However, traditional security techniques cannot be applied to wireless sensor networks. This is due to the constraints of battery power, memory, and the computational capacities of the miniature wireless sensor nodes. Therefore, to address this need, it becomes necessary to develop new lightweight security protocols. This dissertation focuses on designing a suite of lightweight trust-based security mechanisms and a cooperation enforcement protocol for wireless sensor networks. This dissertation presents a trust-based cluster head election mechanism used to elect new cluster heads. This solution prevents a major security breach against the routing protocol, namely, the election of malicious or compromised cluster heads. This dissertation also describes a location-aware, trust-based, compromise node detection, and isolation mechanism. Both of these mechanisms rely on the ability of a node to monitor its neighbors. Using neighbor monitoring techniques, the nodes are able to determine their neighbors’ reputation and trust level through probabilistic modeling. The mechanisms were designed to mitigate internal attacks within wireless sensor networks. The feasibility of the approach is demonstrated through extensive simulations. The dissertation also addresses non-cooperation problems in multi-user wireless sensor networks. A scalable lightweight enforcement algorithm using evolutionary game theory is also designed. The effectiveness of this cooperation enforcement algorithm is validated through mathematical analysis and simulation. This research has advanced the knowledge of wireless sensor network security and cooperation by developing new techniques based on mathematical models. By doing this, we have enabled others to build on our work towards the creation of highly trusted wireless sensor networks. This would facilitate its full utilization in many fields ranging from civilian to military applications.

Trust Based Security Mechanisms for Wireless Sensor Networks

Wireless sensor networks are emerging as effective tools in the gathering and dissemination of data. They can be applied in many fields including health, environmental monitoring, home automation and the military. Like all other computing systems it is necessary to include security features, so that security sensitive data traversing the network is protected. However, traditional security techniques cannot be applied to wireless sensor networks. This is due to the constraints of battery power, memory, and the computational capacities of the miniature wireless sensor nodes. Therefore, to address this need, it becomes necessary to develop new lightweight security protocols. This dissertation focuses on designing a suite of lightweight trust-based security mechanisms and a cooperation enforcement protocol for wireless sensor networks. This dissertation presents a trust-based cluster head election mechanism used to elect new cluster heads. This solution prevents a major security breach against the routing protocol, namely, the election of malicious or compromised cluster heads. This dissertation also describes a location-aware, trust-based, compromise node detection, and isolation mechanism. Both of these mechanisms rely on the ability of a node to monitor its neighbors. Using neighbor monitoring techniques, the nodes are able to determine their neighbors’ reputation and trust level through probabilistic modeling. The mechanisms were designed to mitigate internal attacks within wireless sensor networks. The feasibility of the approach is demonstrated through extensive simulations. The dissertation also addresses non-cooperation problems in multi-user wireless sensor networks. A scalable lightweight enforcement algorithm using evolutionary game theory is also designed. The effectiveness of this cooperation enforcement algorithm is validated through mathematical analysis and simulation. This research has advanced the knowledge of wireless sensor network security and cooperation by developing new techniques based on mathematical models. By doing this, we have enabled others to build on our work towards the creation of highly trusted wireless sensor networks. This would facilitate its full utilization in many fields ranging from civilian to military applications.

A Molecular-scale Programmable Stochastic Process Based On Resonance Energy Transfer Networks: Modeling And Applications

While molecular and cellular processes are often modeled as stochastic processes, such as Brownian motion, chemical reaction networks and gene regulatory networks, there are few attempts to program a molecular-scale process to physically implement stochastic processes. DNA has been used as a substrate for programming molecular interactions, but its applications are restricted to deterministic functions and unfavorable properties such as slow processing, thermal annealing, aqueous solvents and difficult readout limit them to proof-of-concept purposes. To date, whether there exists a molecular process that can be programmed to implement stochastic processes for practical applications remains unknown.

In this dissertation, a fully specified Resonance Energy Transfer (RET) network between chromophores is accurately fabricated via DNA self-assembly, and the exciton dynamics in the RET network physically implement a stochastic process, specifically a continuous-time Markov chain (CTMC), which has a direct mapping to the physical geometry of the chromophore network. Excited by a light source, a RET network generates random samples in the temporal domain in the form of fluorescence photons which can be detected by a photon detector. The intrinsic sampling distribution of a RET network is derived as a phase-type distribution configured by its CTMC model. The conclusion is that the exciton dynamics in a RET network implement a general and important class of stochastic processes that can be directly and accurately programmed and used for practical applications of photonics and optoelectronics. Different approaches to using RET networks exist with vast potential applications. As an entropy source that can directly generate samples from virtually arbitrary distributions, RET networks can benefit applications that rely on generating random samples such as 1) fluorescent taggants and 2) stochastic computing.

By using RET networks between chromophores to implement fluorescent taggants with temporally coded signatures, the taggant design is not constrained by resolvable dyes and has a significantly larger coding capacity than spectrally or lifetime coded fluorescent taggants. Meanwhile, the taggant detection process becomes highly efficient, and the Maximum Likelihood Estimation (MLE) based taggant identification guarantees high accuracy even with only a few hundred detected photons.

Meanwhile, RET-based sampling units (RSU) can be constructed to accelerate probabilistic algorithms for wide applications in machine learning and data analytics. Because probabilistic algorithms often rely on iteratively sampling from parameterized distributions, they can be inefficient in practice on the deterministic hardware traditional computers use, especially for high-dimensional and complex problems. As an efficient universal sampling unit, the proposed RSU can be integrated into a processor / GPU as specialized functional units or organized as a discrete accelerator to bring substantial speedups and power savings.