Inferring slowly changing dynamic gene-regulatory networks

Dynamic gene-regulatory networks are complex since the interaction patterns between its components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a class of models that connect the network with a conditional independence relationships between the random variables. By interpreting the random variables as gene activities and the conditional independence relationships as functional non-relatedness, graphical models have been used to describe gene-regulatory networks. Whereas the literature has been focused on static networks, most time-course experiments are designed in order to tease out temporal changes in the underlying networks. It is typically reasonable to assume that changes in genomic networks are few, because biological systems tend to be stable. We introduce a new model for estimating slowly changes in dynamic gene-regulatory networks, which is suitable for high-dimensional data, e.g. time-course genomic data. Our aim is to estimate a dynamically changing genomic network based on temporal activity measurements of the genes in the network. Our method is based on the penalized likelihood with l1-norm, that penalizes conditional dependencies between genes as well as differences between conditional independence elements across time points. We also present a the heuristic search strategy to find optimal tuning parameters. We re-write the penalized maximum likelihood problem into a standard convex optimization problem subject to linear equality constraints. We show that our method performs well in simulation studies. Finally, we apply the proposed model to a time-course T-cell dataset

Sparse model-based network inference using Gaussian graphical models

We consider the problem of estimating a sparse dynamic Gaussian graphical model with L1 penalized maximum likelihood of structured precision matrix. The structure can consist of specific time dynamics, known presence or absence of links in the graphical model or equality constraints on the parameters. The model is defined on the basis of partial correlations, which results in a specific class precision matrices. A priori L1 penalized maximum likelihood estimation in this class is extremely difficult, because of the above mentioned constraints, the computational complexity of the L1 constraint on the side of the usual positive-definite constraint. The implementation is non-trivial, but we show that the com- putation can be done effectively by taking advantage of an efficient maximum determinant algorithm (SDPT3) developed in convex optimization. For selecting the tuning parameter, we compare several selection criteria and argue that the traditional AIC and BIC should not expect to work. We compare our method with related methods, such as glasso (Friedman et al. 2007)

Generalized information criterion for model selection in penalized graphical models

This paper introduces an estimator of the relative directed distance between an estimated model and the true model, based on the Kulback-Leibler divergence and is motivated by the generalized information criterion proposed by Konishi and Kitagawa. This estimator can be used to select model in penalized Gaussian copula graphical models. The use of this estimator is not feasible for high-dimensional cases. However, we derive an efficient way to compute this estimator which is feasible for the latter class of problems. Moreover, this estimator is, generally, appropriate for several penalties such as lasso, adaptive lasso and smoothly clipped absolute deviation penalty. Simulations show that the method performs similarly to KL oracle estimator and it also improves BIC performance in terms of support recovery of the graph. Specifically, we compare our method with Akaike information criterion, Bayesian information criterion and cross validation for band, sparse and dense network structures

Spatio-temporal spread pattern of Covid-19 in Italy

This paper investigates the spatio-temporal spread pattern of Covid-19 in Italy, during the first wave of infections, from February to October 2020. Disease mappings of the virus infections by using the Besag-York-Molliè model and some spatio-temporal extensions are provided. This modelling framework, which includes a temporal component, allows to study the time evolution of the spread pattern among the 107 Italian provinces. The focus is on the effect of citizens’ mobility patterns, represented here by the three distinct phases of the Italian virus first wave, identified by the Italian government, also characterised by the lockdown period. Results show the effectiveness of the lockdown action and an inhomogeneous spatial trend that characterises the virus spread during the first wave. Furthermore, the results suggest that the temporal evolution of each province’s cases is independent of the temporal evolution of the other ones, meaning that the contagions and temporal trend may be caused by some province-specific aspects rather than by the subjects’ spatial movements

Inferring slowly-changing dynamic gene-regulatory networks

Dynamic gene-regulatory networks are complex since the interaction patterns between their components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a class of models that connect the network with a conditional independence relationships between random variables. By interpreting these random variables as gene activities and the conditional independence relationships as functional non-relatedness, graphical models have been used to describe gene-regulatory networks. Whereas the literature has been focused on static networks, most time-course experiments are designed in order to tease out temporal changes in the underlying network. It is typically reasonable to assume that changes in genomic networks are few, because biological systems tend to be stable. We introduce a new model for estimating slow changes in dynamic gene-regulatory networks, which is suitable for high-dimensional data, e.g. time-course microarray data. Our aim is to estimate a dynamically changing genomic network based on temporal activity measurements of the genes in the network. Our method is based on the penalized likelihood with l1-norm, that penalizes conditional dependencies between genes as well as differences between conditional independence elements across time points. We also present a heuristic search strategy to find optimal tuning parameters. We re-write the penalized maximum likelihood problem into a standard convex optimization problem subject to linear equality constraints. We show that our method performs well in simulation studies. Finally, we apply the proposed model to a time-course T-cell dataset

A computationally fast alternative to cross-validation in penalized Gaussian graphical models

We study the problem of selection of regularization parameter in penalized Gaussian graphical models. When the goal is to obtain a model with good predicting power, cross validation is the gold standard. We present a new estimator of Kullback-Leibler loss in Gaussian Graphical model which provides a computationally fast alternative to cross-validation. The estimator is obtained by approximating leave-one-out-cross validation. Our approach is demonstrated on simulated data sets for various types of graphs. The proposed formula exhibits superior performance, especially in the typical small sample size scenario, compared to other available alternatives to cross validation, such as Akaike’s information criterion and Generalized approximate cross validation. We also show that the estimator can be used to improve the performance of the BIC when the sample size is small

Networks as mediating variables: a Bayesian latent space approach

The use of network analysis to investigate social structures has recently seen a rise due to the high availability of data and the numerous insights it can provide into different fields. Most analyses focus on the topological characteristics of networks and the estimation of relationships between the nodes. We adopt a different perspective by considering the whole network as a random variable conveying the effect of an exposure on a response. This point of view represents a classical mediation setting, where the interest lies in estimating the indirect effect, that is, the effect propagated through the mediating variable. We introduce a latent space model mapping the network into a space of smaller dimension by considering the hidden positions of the units in the network. The coordinates of each node are used as mediators in the relationship between the exposure and the response. We further extend mediation analysis in the latent space framework by using Generalised Linear Models instead of linear ones, as previously done in the literature, adopting an approach based on derivatives to obtain the effects of interest. A Bayesian approach allows us to get the entire distribution of the indirect effect, generally unknown, and compute the corresponding highest density interval, which gives accurate and interpretable bounds for the mediated effect. Finally, an application to social interactions among a group of adolescents and their attitude toward substance use is presented

Chapter Determinants of spatial intensity of stop locations on cruise passengers tracking data

This paper aims at analyzing the spatial intensity in the distribution of stop locations of cruise passengers during their visit at the destination through a stochastic point process modelling approach on a linear network. Data collected through the integration of GPS tracking technology and questionnaire-based survey on cruise passengers visiting the city of Palermo are used, to identify the main determinants which characterize their stop locations pattern. The spatial intensity of stop locations is estimated through a Gibbs point process model, taking into account for both individual-related variables, contextual-level information, and for spatial interaction among stop points. The Berman-Turner device for maximum pseudolikelihood is considered, by using a quadrature scheme generated on the network. The approach used allows taking into account the linear network determined by the street configuration of the destination under analysis. The results show an influence of both socio-demographic and trip-related characteristics on the stop location patterns, as well as the relevance of distance from the main attractions, and potential interactions among cruise passengers in stop configuration. The proposed approach represents both improvements from the methodological perspective, related to the modelling of spatial point process on a linear network, and from the applied perspective, given that better knowledge of the determinants of spatial intensity of visitors’ stop locations in urban contexts may orient destination management policy

Hydrological post-processing based on approximate Bayesian computation (ABC)

[EN] This study introduces a method to quantify the conditional predictive uncertainty in hydrological post-processing contexts when it is cumbersome to calculate the likelihood (intractable likelihood). Sometimes, it can be difficult to calculate the likelihood itself in hydrological modelling, specially working with complex models or with ungauged catchments. Therefore, we propose the ABC post-processor that exchanges the requirement of calculating the likelihood function by the use of some sufficient summary statistics and synthetic datasets. The aim is to show that the conditional predictive distribution is qualitatively similar produced by the exact predictive (MCMC post-processor) or the approximate predictive (ABC post-processor). We also use MCMC post-processor as a benchmark to make results more comparable with the proposed method. We test the ABC post-processor in two scenarios: (1) the Aipe catchment with tropical climate and a spatially-lumped hydrological model (Colombia) and (2) the Oria catchment with oceanic climate and a spatially-distributed hydrological model (Spain). The main finding of the study is that the approximate (ABC post-processor) conditional predictive uncertainty is almost equivalent to the exact predictive (MCMC post-processor) in both scenarios.This study was partially supported by the Departamento del Huila Scholarship Program No. 677 (Colombia) and Colciencias, by the Spanish Research Project TETIS-MED (ref. CGL2014-58127-C3-3-R) and TETIS-CHANGE (ref.RTI2018-093717-B-I00). Also, G. Adelfio's research has been supported by the national grant of the Italian Ministry of Education University and Research (MIUR) for the PRIN-2015 program, "Complex space-time modelling and functional analysis for probabilistic forecast of seismic events'. 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