Differential Equation Models and Numerical Methods for Reverse Engineering Genetic Regulatory Networks

This dissertation develops and analyzes differential equation-based mathematical models and efficient numerical methods and algorithms for genetic regulatory network identification. The primary objectives of the dissertation are to design, analyze, and test a general variational framework and numerical methods for seeking its approximate solutions for reverse engineering genetic regulatory networks from microarray datasets using the approach based on differential equation modeling. In the proposed variational framework, no structure assumption on the genetic network is presumed, instead, the network is solely determined by the microarray profile of the network components and is identified through a well chosen variational principle which minimizes a biological energy functional. The variational principle serves not only as a selection criterion to pick up the right biological solution of the underlying differential equation model but also provide an effective mathematical characterization of the small-world property of genetic regulatory networks which has been observed in lab experiments. Five specific models within the variational framework and efficient numerical methods and algorithms for computing their solutions are proposed and analyzed in the dissertation. Model validations using both synthetic network datasets and real world subnetwork datasets of Saccharomyces cerevisiae (yeast) and E. Coli are done on all five proposed variational models and a performance comparison vs some existing genetic regulatory network identification methods is also provided. As microarray data is typically noisy, in order to take into account the noise effect in the mathematical models, we propose a new approach based on stochastic differential equation modeling and generalize the deterministic variational framework to a stochastic variational framework which relies on stochastic optimization. Numerical algorithms are also proposed for computing solutions of the stochastic variational models. To address the important issue of post-processing computed networks to reflect the small-world property of underlying genetic regulatory networks, a novel threshholding technique based on the Random Matrix Theory is proposed and tested on various synthetic network datasets

Evolutionary improvement of programs

Most applications of genetic programming (GP) involve the creation of an entirely new function, program or expression to solve a specific problem. In this paper, we propose a new approach that applies GP to improve existing software by optimizing its non-functional properties such as execution time, memory usage, or power consumption. In general, satisfying non-functional requirements is a difficult task and often achieved in part by optimizing compilers. However, modern compilers are in general not always able to produce semantically equivalent alternatives that optimize non-functional properties, even if such alternatives are known to exist: this is usually due to the limited local nature of such optimizations. In this paper, we discuss how best to combine and extend the existing evolutionary methods of GP, multiobjective optimization, and coevolution in order to improve existing software. Given as input the implementation of a function, we attempt to evolve a semantically equivalent version, in this case optimized to reduce execution time subject to a given probability distribution of inputs. We demonstrate that our framework is able to produce non-obvious optimizations that compilers are not yet able to generate on eight example functions. We employ a coevolved population of test cases to encourage the preservation of the function's semantics. We exploit the original program both through seeding of the population in order to focus the search, and as an oracle for testing purposes. As well as discussing the issues that arise when attempting to improve software, we employ rigorous experimental method to provide interesting and practical insights to suggest how to address these issues

Genetic Programming for Smart Phone Personalisation

Personalisation in smart phones requires adaptability to dynamic context based on user mobility, application usage and sensor inputs. Current personalisation approaches, which rely on static logic that is developed a priori, do not provide sufficient adaptability to dynamic and unexpected context. This paper proposes genetic programming (GP), which can evolve program logic in realtime, as an online learning method to deal with the highly dynamic context in smart phone personalisation. We introduce the concept of collaborative smart phone personalisation through the GP Island Model, in order to exploit shared context among co-located phone users and reduce convergence time. We implement these concepts on real smartphones to demonstrate the capability of personalisation through GP and to explore the benefits of the Island Model. Our empirical evaluations on two example applications confirm that the Island Model can reduce convergence time by up to two-thirds over standalone GP personalisation.Comment: 43 pages, 11 figure

Multi-objective improvement of software using co-evolution and smart seeding

Optimising non-functional properties of software is an important part of the implementation process. One such property is execution time, and compilers target a reduction in execution time using a variety of optimisation techniques. Compiler optimisation is not always able to produce semantically equivalent alternatives that improve execution times, even if such alternatives are known to exist. Often, this is due to the local nature of such optimisations. In this paper we present a novel framework for optimising existing software using a hybrid of evolutionary optimisation techniques. Given as input the implementation of a program or function, we use Genetic Programming to evolve a new semantically equivalent version, optimised to reduce execution time subject to a given probability distribution of inputs. We employ a co-evolved population of test cases to encourage the preservation of the program’s semantics, and exploit the original program through seeding of the population in order to focus the search. We carry out experiments to identify the important factors in maximising efficiency gains. Although in this work we have optimised execution time, other non-functional criteria could be optimised in a similar manner

A Multi-Gene Genetic Programming Application for Predicting Students Failure at School

Several efforts to predict student failure rate (SFR) at school accurately still remains a core problem area faced by many in the educational sector. The procedure for forecasting SFR are rigid and most often times require data scaling or conversion into binary form such as is the case of the logistic model which may lead to lose of information and effect size attenuation. Also, the high number of factors, incomplete and unbalanced dataset, and black boxing issues as in Artificial Neural Networks and Fuzzy logic systems exposes the need for more efficient tools. Currently the application of Genetic Programming (GP) holds great promises and has produced tremendous positive results in different sectors. In this regard, this study developed GPSFARPS, a software application to provide a robust solution to the prediction of SFR using an evolutionary algorithm known as multi-gene genetic programming. The approach is validated by feeding a testing data set to the evolved GP models. Result obtained from GPSFARPS simulations show its unique ability to evolve a suitable failure rate expression with a fast convergence at 30 generations from a maximum specified generation of 500. The multi-gene system was also able to minimize the evolved model expression and accurately predict student failure rate using a subset of the original expressionComment: 14 pages, 9 figures, Journal paper. arXiv admin note: text overlap with arXiv:1403.0623 by other author