Combining Bayesian Approaches and Evolutionary Techniques for the Inference of Breast Cancer Networks

Gene and protein networks are very important to model complex large-scale systems in molecular biology. Inferring or reverseengineering such networks can be defined as the process of identifying gene/protein interactions from experimental data through computational analysis. However, this task is typically complicated by the enormously large scale of the unknowns in a rather small sample size. Furthermore, when the goal is to study causal relationships within the network, tools capable of overcoming the limitations of correlation networks are required. In this work, we make use of Bayesian Graphical Models to attach this problem and, specifically, we perform a comparative study of different state-of-the-art heuristics, analyzing their performance in inferring the structure of the Bayesian Network from breast cancer data

Deterministic Effects Propagation Networks for reconstructing protein signaling networks from multiple interventions

<p>Abstract</p> <p>Background</p> <p>Modern gene perturbation techniques, like RNA interference (RNAi), enable us to study effects of targeted interventions in cells efficiently. In combination with mRNA or protein expression data this allows to gain insights into the behavior of complex biological systems.</p> <p>Results</p> <p>In this paper, we propose Deterministic Effects Propagation Networks (DEPNs) as a special Bayesian Network approach to reverse engineer signaling networks from a combination of protein expression and perturbation data. DEPNs allow to reconstruct protein networks based on combinatorial intervention effects, which are monitored via changes of the protein expression or activation over one or a few time points. Our implementation of DEPNs allows for latent network nodes (i.e. proteins without measurements) and has a built in mechanism to impute missing data. The robustness of our approach was tested on simulated data. We applied DEPNs to reconstruct the <it>ERBB </it>signaling network in <it>de novo </it>trastuzumab resistant human breast cancer cells, where protein expression was monitored on Reverse Phase Protein Arrays (RPPAs) after knockdown of network proteins using RNAi.</p> <p>Conclusion</p> <p>DEPNs offer a robust, efficient and simple approach to infer protein signaling networks from multiple interventions. The method as well as the data have been made part of the latest version of the R package "nem" available as a supplement to this paper and via the Bioconductor repository.</p

Network and biosignature analysis for the integration of transcriptomic and metabolomic data to characterize leaf senescence process in sunflower

In recent years, high throughput technologies have led to an increase of datasets from omics disciplines allowing the understanding of the complex regulatory networks associated with biological processes. Leaf senescence is a complex mechanism controlled by multiple genetic and environmental variables, which has a strong impact on crop yield. Transcription factors (TFs) are key proteins in the regulation of gene expression, regulating different signaling pathways; their function is crucial for triggering and/or regulating different aspects of the leaf senescence process. The study of TF interactions and their integration with metabolic profiles under different developmental conditions, especially for a non-model organism such as sunflower, will open new insights into the details of gene regulation of leaf senescence.Fil: Moschen, Sebastián Nicolás. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Higgins, Janet. The Genome Analysis Centre; Reino UnidoFil: Di Rienzo, Julio Alejandro. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias; ArgentinaFil: Heinz, Ruth Amelia. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paniego, Norma Beatriz. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Paula del Carmen. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Memetic micro-genetic algorithms for cancer data classification

Fast and precise medical diagnosis of human cancer is crucial for treatment decisions. Gene selection consists of identifying a set of informative genes from microarray data to allow high predictive accuracy in human cancer classification. This task is a combinatorial search problem, and optimisation methods can be applied for its resolution. In this paper, two memetic micro-genetic algorithms (MμV1 and MμV2) with different hybridisation approaches are proposed for feature selection of cancer microarray data. Seven gene expression datasets are used for experimentation. The comparison with stochastic state-of-the-art optimisation techniques concludes that problem-dependent local search methods combined with micro-genetic algorithms improve feature selection of cancer microarray data.Fil: Rojas, Matias Gabriel. Universidad Nacional de Lujan. Centro de Investigacion Docencia y Extension En Tecnologias de la Informacion y Las Comunicaciones.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Olivera, Ana Carolina. Universidad Nacional de Cuyo. Facultad de Ingeniería; Argentina. Universidad Nacional de Lujan. Centro de Investigacion Docencia y Extension En Tecnologias de la Informacion y Las Comunicaciones.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Carballido, Jessica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias e Ingeniería de la Computación; ArgentinaFil: Vidal, Pablo Javier. Universidad Nacional de Cuyo. Facultad de Ingeniería; Argentina. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentin

Improving the efficiency of Bayesian Network Based EDAs and their application in Bioinformatics

Estimation of distribution algorithms (EDAs) is a relatively new trend of stochastic optimizers which have received a lot of attention during last decade. In each generation, EDAs build probabilistic models of promising solutions of an optimization problem to guide the search process. New sets of solutions are obtained by sampling the corresponding probability distributions. Using this approach, EDAs are able to provide the user a set of models that reveals the dependencies between variables of the optimization problems while solving them. In order to solve a complex problem, it is necessary to use a probabilistic model which is able to capture the dependencies. Bayesian networks are usually used for modeling multiple dependencies between variables. Learning Bayesian networks, especially for large problems with high degree of dependencies among their variables is highly computationally expensive which makes it the bottleneck of EDAs. Therefore introducing efficient Bayesian learning algorithms in EDAs seems necessary in order to use them for large problems. In this dissertation, after comparing several Bayesian network learning algorithms, we propose an algorithm, called CMSS-BOA, which uses a recently introduced heuristic called max-min parent children (MMPC) in order to constrain the model search space. This algorithm does not consider a fixed and small upper bound on the order of interaction between variables and is able solve problems with large numbers of variables efficiently. We compare the efficiency of CMSS-BOA with the standard Bayesian network based EDA for solving several benchmark problems and finally we use it to build a predictor for predicting the glycation sites in mammalian proteins

Constraint-based probabilistic learning of metabolic pathways from tomato volatiles

Clustering and correlation analysis techniques have become popular tools for the analysis of data produced by metabolomics experiments. The results obtained from these approaches provide an overview of the interactions between objects of interest. Often in these experiments, one is more interested in information about the nature of these relationships, e.g., cause-effect relationships, than in the actual strength of the interactions. Finding such relationships is of crucial importance as most biological processes can only be understood in this way. Bayesian networks allow representation of these cause-effect relationships among variables of interest in terms of whether and how they influence each other given that a third, possibly empty, group of variables is known. This technique also allows the incorporation of prior knowledge as established from the literature or from biologists. The representation as a directed graph of these relationship is highly intuitive and helps to understand these processes. This paper describes how constraint-based Bayesian networks can be applied to metabolomics data and can be used to uncover the important pathways which play a significant role in the ripening of fresh tomatoes. We also show here how this methods of reconstructing pathways is intuitive and performs better than classical techniques. Methods for learning Bayesian network models are powerful tools for the analysis of data of the magnitude as generated by metabolomics experiments. It allows one to model cause-effect relationships and helps in understanding the underlying processes

A temporal prognostic model based on dynamic Bayesian networks: mining medical insurance data

A prognostic model is a formal combination of multiple predictors from which risk probability of a specific diagnosis can be modelled for patients. Prognostic models have become essential instruments in medicine. The models are used for prediction purposes of guiding doctors to make a smart diagnosis, patient-specific decisions or help in planning the utilization of resources for patient groups who have similar prognostic paths. Dynamic Bayesian networks theoretically provide a very expressive and flexible model to solve temporal problems in medicine. However, this involves various challenges due both to the nature of the clinical domain, and the nature of the DBN modelling and inference process itself. The challenges from the clinical domain include insufficient knowledge of temporal interactions of processes in the medical literature, the sparse nature and variability of medical data collection, and the difficulty in preparing and abstracting clinical data in a suitable format without losing valuable information in the process. Challenges about the DBN methodology and implementation include the lack of tools that allow easy modelling of temporal processes. Overcoming this challenge will help to solve various clinical temporal reasoning problems. In this thesis, we addressed these challenges while building a temporal network with explanations of the effects of predisposing factors, such as age and gender, and the progression information of all diagnoses using claims data from an insurance company in Kenya. We showed that our network could differentiate the possible probability exposure to a diagnosis given the age and gender and possible paths given a patient's history. We also presented evidence that the more patient history is provided, the better the prediction of future diagnosis