Knowledge-fused differential dependency network models for detecting significant rewiring in biological networks

Modeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context specific and dynamic in nature. To systematically characterize the selectively activated regulatory components and mechanisms, the modeling tools must be able to effectively distinguish significant rewiring from random background fluctuations. We formulated the inference of differential dependency networks that incorporates both conditional data and prior knowledge as a convex optimization problem, and developed an efficient learning algorithm to jointly infer the conserved biological network and the significant rewiring across different conditions. We used a novel sampling scheme to estimate the expected error rate due to random knowledge and based on which, developed a strategy that fully exploits the benefit of this data-knowledge integrated approach. We demonstrated and validated the principle and performance of our method using synthetic datasets. We then applied our method to yeast cell line and breast cancer microarray data and obtained biologically plausible results.Comment: 7 pages, 7 figure

Fusión de redes Bayesianas Gaussianas

Las redes Bayesianas constituyen un modelo ampliamente utilizado para la representación de relaciones de dependencia condicional en datos multivariantes. Su aprendizaje a partir de un conjunto de datos o expertos ha sido estudiado profundamente desde su concepción. Sin embargo, en determinados escenarios se demanda la obtención de un modelo común asociado a particiones de datos o conjuntos de expertos. En este caso, se trata el problema de fusión o agregación de modelos. Los trabajos y resultados en agregación de redes Bayesianas son de naturaleza variada, aunque escasos en comparación con aquellos de aprendizaje. En este documento, se proponen dos métodos para la agregación de redes Gaussianas, definidas como aquellas redes Bayesianas que modelan una distribución Gaussiana multivariante. Los métodos presentados son efectivos, precisos y producen redes con menor cantidad de parámetros en comparación con los modelos obtenidos individualmente. Además, constituyen un enfoque novedoso al incorporar nociones exploradas tradicionalmente por separado en el estado del arte. Futuras aplicaciones en entornos escalables hacen dichos métodos especialmente atractivos, dada su simplicidad y la ganancia en compacidad de la representación obtenida.---ABSTRACT---Bayesian networks are a widely used model for the representation of conditional dependence relationships among variables in multivariate data. The task of learning them from a data set or experts has been deeply studied since their conception. However, situations emerge where there is a need of obtaining a consensuated model from several data partitions or a set of experts. This situation is referred to as model fusion or aggregation. Results about Bayesian network aggregation, although rich in variety, have been scarce when compared to the learning task. In this context, two methods are proposed for the aggregation of Gaussian Bayesian networks, that is, Bayesian networks whose underlying modelled distribution is a multivariate Gaussian. Both methods are effective, precise and produce networks with fewer parameters in comparison with the models obtained by individual learning. They constitute a novel approach given that they incorporate notions traditionally explored separately in the state of the art. Future applications in scalable computer environments make such models specially attractive, given their simplicity and the gaining in sparsity of the produced model