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Designing synthetic networks in silico: a generalised evolutionary algorithm approach.

ABSTRACT: Evolution has led to the development of biological networks that are shaped by environmental signals. Elucidating, understanding and then reconstructing important network motifs is one of the principal aims of Systems & Synthetic Biology. Consequently, previous research has focused on finding optimal network structures and reaction rates that respond to pulses or produce stable oscillations. In this work we present a generalised in silico evolutionary algorithm that simultaneously finds network structures and reaction rates (genotypes) that can satisfy multiple defined objectives (phenotypes).The key step to our approach is to translate a schema/binary-based description of biological networks into systems of ordinary differential equations (ODEs). The ODEs can then be solved numerically to provide dynamic information about an evolved networks functionality. Initially we benchmark algorithm performance by finding optimal networks that can recapitulate concentration time-series data and perform parameter optimisation on oscillatory dynamics of the Repressilator. We go on to show the utility of our algorithm by finding new designs for robust synthetic oscillators, and by performing multi-objective optimisation to find a set of oscillators and feed-forward loops that are optimal at balancing different system properties. In sum, our results not only confirm and build on previous observations but we also provide new designs of synthetic oscillators for experimental construction.In this work we have presented and tested an evolutionary algorithm that can design a biological network to produce desired output. Given that previous designs of synthetic networks have been limited to subregions of network- and parameter-space, the use of our evolutionary optimisation algorithm will enable Synthetic Biologists to construct new systems with the potential to display a wider range of complex responses.

SUBMITTER: Smith RW

PROVIDER: S-EPMC5712201 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Designing synthetic networks in silico: a generalised evolutionary algorithm approach.

Smith Robert W RW van Sluijs Bob B Fleck Christian C

BMC systems biology 20171202 1

<h4>Background</h4>Evolution has led to the development of biological networks that are shaped by environmental signals. Elucidating, understanding and then reconstructing important network motifs is one of the principal aims of Systems & Synthetic Biology. Consequently, previous research has focused on finding optimal network structures and reaction rates that respond to pulses or produce stable oscillations. In this work we present a generalised in silico evolutionary algorithm that simultaneo ...[more]

PMID: 29197394

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Project description:To design an algorithm for detecting outliers over streaming data has become an important task in many common applications, arising in areas such as fraud detections, network analysis, environment monitoring and so forth. Due to the fact that real-time data may arrive in the form of streams rather than batches, properties such as concept drift, temporal context, transiency, and uncertainty need to be considered. In addition, data processing needs to be incremental with limited memory resource, and scalable. These facts create big challenges for existing outlier detection algorithms in terms of their accuracies when they are implemented in an incremental fashion, especially in the streaming environment. To address these problems, we first propose C_KDE_WR, which uses sliding window and kernel function to process the streaming data online, and reports its results demonstrating high throughput on handling real-time streaming data, implemented in a CUDA framework on Graphics Processing Unit (GPU). We also present another algorithm, C_LOF, based on a very popular and effective outlier detection algorithm called Local Outlier Factor (LOF) which unfortunately works only on batched data. Using a novel incremental approach that compensates the drawback of high complexity in LOF, we show how to implement it in a streaming context and to obtain results in a timely manner. Like C_KDE_WR, C_LOF also employs sliding-window and statistical-summary to help making decision based on the data in the current window. It also addresses all those challenges of streaming data as addressed in C_KDE_WR. In addition, we report the comparative evaluation on the accuracy of C_KDE_WR with the state-of-the-art SOD_GPU using Precision, Recall and F-score metrics. Furthermore, a t-test is also performed to demonstrate the significance of the improvement. We further report the testing results of C_LOF on different parameter settings and drew ROC and PR curve with their area under the curve (AUC) and Average Precision (AP) values calculated respectively. Experimental results show that C_LOF can overcome the masquerading problem, which often exists in outlier detection on streaming data. We provide complexity analysis and report experiment results on the accuracy of both C_KDE_WR and C_LOF algorithms in order to evaluate their effectiveness as well as their efficiencies.

Project description:BACKGROUND:The future of medicine is moving towards the phase of precision medicine, with the goal to prevent and treat diseases by taking inter-individual variability into account. A large part of the variability lies in our genetic makeup. With the fast paced improvement of high-throughput methods for genome sequencing, a tremendous amount of genetics data have already been generated. The next hurdle for precision medicine is to have sufficient computational tools for analyzing large sets of data. Genome-Wide Association Studies (GWAS) have been the primary method to assess the relationship between single nucleotide polymorphisms (SNPs) and disease traits. While GWAS is sufficient in finding individual SNPs with strong main effects, it does not capture potential interactions among multiple SNPs. In many traits, a large proportion of variation remain unexplained by using main effects alone, leaving the door open for exploring the role of genetic interactions. However, identifying genetic interactions in large-scale genomics data poses a challenge even for modern computing. RESULTS:For this study, we present a new algorithm, Grammatical Evolution Bayesian Network (GEBN) that utilizes Bayesian Networks to identify interactions in the data, and at the same time, uses an evolutionary algorithm to reduce the computational cost associated with network optimization. GEBN excelled in simulation studies where the data contained main effects and interaction effects. We also applied GEBN to a Type 2 diabetes (T2D) dataset obtained from the Marshfield Personalized Medicine Research Project (PMRP). We were able to identify genetic interactions for T2D cases and controls and use information from those interactions to classify T2D samples. We obtained an average testing area under the curve (AUC) of 86.8 %. We also identified several interacting genes such as INADL and LPP that are known to be associated with T2D. CONCLUSIONS:Developing the computational tools to explore genetic associations beyond main effects remains a critically important challenge in human genetics. Methods, such as GEBN, demonstrate the utility of considering genetic interactions, as they likely explain some of the missing heritability.

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Designing synthetic networks in silico: a generalised evolutionary algorithm approach.

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Designing synthetic networks in silico: a generalised evolutionary algorithm approach.

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