Inferring cellular networks – a review

In this review we give an overview of computational and statistical methods to reconstruct cellular networks. Although this area of research is vast and fast developing, we show that most currently used methods can be organized by a few key concepts. The first part of the review deals with conditional independence models including Gaussian graphical models and Bayesian networks. The second part discusses probabilistic and graph-based methods for data from experimental interventions and perturbations

Combining gene expression data and prior knowledge for inferring gene regulatory networks via Bayesian networks using structural restrictions

Ministerio de Economía y Competitividad y Fondo Europeo de Desarrollo Regional (FEDER), proyectos TEC2015-69496-R y TIN2016-77902-C3-2-

Multiple Quantitative Trait Analysis Using Bayesian Networks

Models for genome-wide prediction and association studies usually target a single phenotypic trait. However, in animal and plant genetics it is common to record information on multiple phenotypes for each individual that will be genotyped. Modeling traits individually disregards the fact that they are most likely associated due to pleiotropy and shared biological basis, thus providing only a partial, confounded view of genetic effects and phenotypic interactions. In this paper we use data from a Multiparent Advanced Generation Inter-Cross (MAGIC) winter wheat population to explore Bayesian networks as a convenient and interpretable framework for the simultaneous modeling of multiple quantitative traits. We show that they are equivalent to multivariate genetic best linear unbiased prediction (GBLUP), and that they are competitive with single-trait elastic net and single-trait GBLUP in predictive performance. Finally, we discuss their relationship with other additive-effects models and their advantages in inference and interpretation. MAGIC populations provide an ideal setting for this kind of investigation because the very low population structure and large sample size result in predictive models with good power and limited confounding due to relatedness.Comment: 28 pages, 1 figure, code at http://www.bnlearn.com/research/genetics1

Efficient computational strategies to learn the structure of probabilistic graphical models of cumulative phenomena

Structural learning of Bayesian Networks (BNs) is a NP-hard problem, which is further complicated by many theoretical issues, such as the I-equivalence among different structures. In this work, we focus on a specific subclass of BNs, named Suppes-Bayes Causal Networks (SBCNs), which include specific structural constraints based on Suppes' probabilistic causation to efficiently model cumulative phenomena. Here we compare the performance, via extensive simulations, of various state-of-the-art search strategies, such as local search techniques and Genetic Algorithms, as well as of distinct regularization methods. The assessment is performed on a large number of simulated datasets from topologies with distinct levels of complexity, various sample size and different rates of errors in the data. Among the main results, we show that the introduction of Suppes' constraints dramatically improve the inference accuracy, by reducing the solution space and providing a temporal ordering on the variables. We also report on trade-offs among different search techniques that can be efficiently employed in distinct experimental settings. This manuscript is an extended version of the paper "Structural Learning of Probabilistic Graphical Models of Cumulative Phenomena" presented at the 2018 International Conference on Computational Science

Data- and knowledge-based modeling of gene regulatory networks: an update

Gene regulatory network inference is a systems biology approach which predicts interactions between genes with the help of high-throughput data. In this review, we present current and updated network inference methods focusing on novel techniques for data acquisition, network inference assessment, network inference for interacting species and the integration of prior knowledge. After the advance of Next-Generation-Sequencing of cDNAs derived from RNA samples (RNA-Seq) we discuss in detail its application to network inference. Furthermore, we present progress for large-scale or even full-genomic network inference as well as for small-scale condensed network inference and review advances in the evaluation of network inference methods by crowdsourcing. Finally, we reflect the current availability of data and prior knowledge sources and give an outlook for the inference of gene regulatory networks that reflect interacting species, in particular pathogen-host interactions

Reconstruction of metabolic pathways by combining probabilistic graphical model-based and knowledge-based methods

Automatic reconstruction of metabolic pathways for an organism from genomics and transcriptomics data has been a challenging and important problem in bioinformatics. Traditionally, known reference pathways can be mapped into an organism-specific ones based on its genome annotation and protein homology. However, this simple knowledge-based mapping method might produce incomplete pathways and generally cannot predict unknown new relations and reactions. In contrast, ab initio metabolic network construction methods can predict novel reactions and interactions, but its accuracy tends to be low leading to a lot of false positives. Here we combine existing pathway knowledge and a new ab initio Bayesian probabilistic graphical model together in a novel fashion to improve automatic reconstruction of metabolic networks. Specifically, we built a knowledge database containing known, individual gene / protein interactions and metabolic reactions extracted from existing reference pathways. Known reactions and interactions were then used as constraints for Bayesian network learning methods to predict metabolic pathways. Using individual reactions and interactions extracted from different pathways of many organisms to guide pathway construction is new and improves both the coverage and accuracy of metabolic pathway construction. We applied this probabilistic knowledge-based approach to construct the metabolic networks from yeast gene expression data and compared its results with 62 known metabolic networks in the KEGG database. The experiment showed that the method improved the coverage of metabolic network construction over the traditional reference pathway mapping method and was more accurate than pure ab initio methods

Learning the structure of Bayesian Networks: A quantitative assessment of the effect of different algorithmic schemes

One of the most challenging tasks when adopting Bayesian Networks (BNs) is the one of learning their structure from data. This task is complicated by the huge search space of possible solutions, and by the fact that the problem is NP-hard. Hence, full enumeration of all the possible solutions is not always feasible and approximations are often required. However, to the best of our knowledge, a quantitative analysis of the performance and characteristics of the different heuristics to solve this problem has never been done before. For this reason, in this work, we provide a detailed comparison of many different state-of-the-arts methods for structural learning on simulated data considering both BNs with discrete and continuous variables, and with different rates of noise in the data. In particular, we investigate the performance of different widespread scores and algorithmic approaches proposed for the inference and the statistical pitfalls within them