Efficient partially observable markov decision process based formulation of gene regulatory network control problem

Erdoğdu, Utku
The need to analyze and closely study the gene related mechanisms motivated the research on the modeling and control of gene regulatory networks (GRN). Di erent approaches exist to model GRNs; they are mostly simulated as mathematical models that represent relationships between genes. Though it turns into a more challenging problem, we argue that partial observability would be a more natural and realistic method for handling the control of GRNs. Partial observability is a fundamental aspect of the problem; it is mostly ignored and substituted by the assumption that states of GRN are known precisely, prescribed as full observability. On the other hand, current works addressing partially observability focus on formulating algorithms for the nite horizon GRN control problem. So, in this work we explore the feasibility of realizing the problem in a partially observable setting, mainly with Partially Observable Markov Decision Processes (POMDP). We proposed a POMDP formulation for the in nite horizon version of the problem. Knowing the fact that POMDP problems su er from the curse of dimensionality, we also proposed a POMDP solution method that automatically decomposes the problem by isolating di erent unrelated parts of the problem, and then solves the reduced subproblems. We also proposed a method to enrich gene expression data sets given as input to POMDP control task, because in available data sets there are thousands of genes but only tens or rarely hundreds of samples. The method is based on the idea of generating more than one model using the available data sets, and then sampling data from each of the models and nally ltering the generated samples with the help of metrics that measure compatibility, diversity and coverage of the newly generated samples.


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Inference of gene regulatory or signaling networks from perturbation experiments and gene expression assays is one of the challenging problems in bioinformatics. Recently, the inference problem has been formulated as a reference network editing problem and it has been show that finding the minimum number of edit operations on a reference network in order to comply with perturbation experiments is an NP-complete problem. In this dissertation, we propose linear programming based solutions for reconstruction o...
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Gene regulatory networks (GRNs) govern the protein transcription process in the cell and interactions among genes play a vital role in determining the biosynthesis rate of proteins. By using intervention techniques discovered by biological research it is possible to control a GRN, thus promoting or demoting the expression rate of a certain gene. In this work, this control task is studied in a partially observable setting where interventions lack perfect knowledge of the expression level of all genes. Moreov...
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Yılmaz, Fatih; Öktem, Hüseyin Avni (2004-09-03)
This study concerns modeling, approximation and inference of gene regulatory dynamics on the basis of gene expression patterns. The dynamical behavior of gene expressions is represented by a system of ordinary differential equations. We introduce a gene-interaction matrix with some nonlinear entries, in particular, quadratic polynomials of the expression levels to keep the system solvable. The model parameters are determined by using optimization. Then, we provide the time-discrete approximation of our time...
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Şirin, Utku; Polat, Faruk; Department of Computer Engineering (2013)
Over the last decade, modeling and controlling gene regulation has received much attention. In this thesis, we have attempted to solve (i) controlling gene regulation systems and (ii) generating high quality artificial gene expression data problems. For controlling gene regulation systems, we have proposed three control solutions based on Batch Mode Reinforcement Learning (Batch RL) techniques. We have proposed one control solution for fully, and two control solutions for partially observable gene regulatio...
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Citation Formats
U. Erdoğdu, “Efficient partially observable markov decision process based formulation of gene regulatory network control problem,” Ph.D. - Doctoral Program, Middle East Technical University, 2012.