27,114 research outputs found
Multicriteria global optimization for biocircuit design
One of the challenges in Synthetic Biology is to design circuits with
increasing levels of complexity. While circuits in Biology are complex and
subject to natural tradeoffs, most synthetic circuits are simple in terms of
the number of regulatory regions, and have been designed to meet a single
design criterion. In this contribution we introduce a multiobjective
formulation for the design of biocircuits. We set up the basis for an advanced
optimization tool for the modular and systematic design of biocircuits capable
of handling high levels of complexity and multiple design criteria. Our
methodology combines the efficiency of global Mixed Integer Nonlinear
Programming solvers with multiobjective optimization techniques. Through a
number of examples we show the capability of the method to generate non
intuitive designs with a desired functionality setting up a priori the desired
level of complexity. The presence of more than one competing objective provides
a realistic design setting where every design solution represents a trade-off
between different criteria. The tool can be useful to explore and identify
different design principles for synthetic gene circuits
Detection of regulator genes and eQTLs in gene networks
Genetic differences between individuals associated to quantitative phenotypic
traits, including disease states, are usually found in non-coding genomic
regions. These genetic variants are often also associated to differences in
expression levels of nearby genes (they are "expression quantitative trait
loci" or eQTLs for short) and presumably play a gene regulatory role, affecting
the status of molecular networks of interacting genes, proteins and
metabolites. Computational systems biology approaches to reconstruct causal
gene networks from large-scale omics data have therefore become essential to
understand the structure of networks controlled by eQTLs together with other
regulatory genes, and to generate detailed hypotheses about the molecular
mechanisms that lead from genotype to phenotype. Here we review the main
analytical methods and softwares to identify eQTLs and their associated genes,
to reconstruct co-expression networks and modules, to reconstruct causal
Bayesian gene and module networks, and to validate predicted networks in
silico.Comment: minor revision with typos corrected; review article; 24 pages, 2
figure
Parameter estimation for Boolean models of biological networks
Boolean networks have long been used as models of molecular networks and play
an increasingly important role in systems biology. This paper describes a
software package, Polynome, offered as a web service, that helps users
construct Boolean network models based on experimental data and biological
input. The key feature is a discrete analog of parameter estimation for
continuous models. With only experimental data as input, the software can be
used as a tool for reverse-engineering of Boolean network models from
experimental time course data.Comment: Web interface of the software is available at
http://polymath.vbi.vt.edu/polynome
Delay-Based Controller Design for Continuous-Time and Hybrid Applications
Motivated by the availability of different types of delays in embedded systems and biological circuits, the objective of this work is to study the benefits that delay can provide in simplifying the implementation of controllers for continuous-time systems. Given a continuous-time linear time-invariant (LTI) controller, we propose three methods to approximate this controller arbitrarily precisely by a simple controller composed of delay blocks, a few integrators and possibly a unity feedback. Different problems associated with the approximation procedures, such as finding the optimal number of delay blocks or studying the robustness of the designed controller with respect to delay values, are then investigated. We also study the design of an LTI continuous-time controller satisfying given control objectives whose delay-based implementation needs the least number of delay blocks. A direct application of this work is in the sampled-data control of a real-time embedded system, where the sampling frequency is relatively high and/or the output of the system is sampled irregularly. Based on our results on delay-based controller design, we propose a digital-control scheme that can implement every continuous-time stabilizing (LTI)
controller. Unlike a typical sampled-data controller, the hybrid controller introduced here -— consisting of an ideal sampler, a digital controller, a number of modified second-order holds and possibly a unity feedback -— is robust to sampling jitter and can operate at arbitrarily high sampling frequencies without requiring expensive, high-precision computation
Systems approaches and algorithms for discovery of combinatorial therapies
Effective therapy of complex diseases requires control of highly non-linear
complex networks that remain incompletely characterized. In particular, drug
intervention can be seen as control of signaling in cellular networks.
Identification of control parameters presents an extreme challenge due to the
combinatorial explosion of control possibilities in combination therapy and to
the incomplete knowledge of the systems biology of cells. In this review paper
we describe the main current and proposed approaches to the design of
combinatorial therapies, including the empirical methods used now by clinicians
and alternative approaches suggested recently by several authors. New
approaches for designing combinations arising from systems biology are
described. We discuss in special detail the design of algorithms that identify
optimal control parameters in cellular networks based on a quantitative
characterization of control landscapes, maximizing utilization of incomplete
knowledge of the state and structure of intracellular networks. The use of new
technology for high-throughput measurements is key to these new approaches to
combination therapy and essential for the characterization of control
landscapes and implementation of the algorithms. Combinatorial optimization in
medical therapy is also compared with the combinatorial optimization of
engineering and materials science and similarities and differences are
delineated.Comment: 25 page
Parameters identification of unknown delayed genetic regulatory networks by a switching particle swarm optimization algorithm
The official published version can be found at the link below.This paper presents a novel particle swarm optimization (PSO) algorithm based on Markov chains and competitive penalized method. Such an algorithm is developed to solve global optimization problems with applications in identifying unknown parameters of a class of genetic regulatory networks (GRNs). By using an evolutionary factor, a new switching PSO (SPSO) algorithm is first proposed and analyzed, where the velocity updating equation jumps from one mode to another according to a Markov chain, and acceleration coefficients are dependent on mode switching. Furthermore, a leader competitive penalized multi-learning approach (LCPMLA) is introduced to improve the global search ability and refine the convergent solutions. The LCPMLA can automatically choose search strategy using a learning and penalizing mechanism. The presented SPSO algorithm is compared with some well-known PSO algorithms in the experiments. It is shown that the SPSO algorithm has faster local convergence speed, higher accuracy and algorithm reliability, resulting in better balance between the global and local searching of the algorithm, and thus generating good performance. Finally, we utilize the presented SPSO algorithm to identify not only the unknown parameters but also the coupling topology and time-delay of a class of GRNs.This research was partially supported by the National Natural Science Foundation of PR China (Grant No. 60874113), the Research Fund for the Doctoral Program of Higher Education (Grant No. 200802550007), the Key Creative Project of Shanghai Education Community (Grant No. 09ZZ66), the Key Foundation Project of Shanghai (Grant No. 09JC1400700), the Engineering and Physical Sciences Research Council EPSRC of the UK under Grant No. GR/S27658/01, the International Science and Technology Cooperation Project of China under Grant No. 2009DFA32050, an International Joint Project sponsored by the Royal Society of the UK, and the Alexander von Humboldt Foundation of Germany
Review of trends and targets of complex systems for power system optimization
Optimization systems (OSs) allow operators of electrical power systems (PS) to optimally operate PSs and to also create optimal PS development plans. The inclusion of OSs in the PS is a big trend nowadays, and the demand for PS optimization tools and PS-OSs experts is growing. The aim of this review is to define the current dynamics and trends in PS optimization research and to present several papers that clearly and comprehensively describe PS OSs with characteristics corresponding to the identified current main trends in this research area. The current dynamics and trends of the research area were defined on the basis of the results of an analysis of the database of 255 PS-OS-presenting papers published from December 2015 to July 2019. Eleven main characteristics of the current PS OSs were identified. The results of the statistical analyses give four characteristics of PS OSs which are currently the most frequently presented in research papers: OSs for minimizing the price of electricity/OSs reducing PS operation costs, OSs for optimizing the operation of renewable energy sources, OSs for regulating the power consumption during the optimization process, and OSs for regulating the energy storage systems operation during the optimization process. Finally, individual identified characteristics of the current PS OSs are briefly described. In the analysis, all PS OSs presented in the observed time period were analyzed regardless of the part of the PS for which the operation was optimized by the PS OS, the voltage level of the optimized PS part, or the optimization goal of the PS OS.Web of Science135art. no. 107
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