arXiv subjects

Matthieu Vignes

Publications and source records attributed to Matthieu Vignes.

5 recordsLinked to original sources

arXiv2018

Causal Queries from Observational Data in Biological Systems via Bayesian Networks: An Empirical Study in Small Networks

Biological networks are a very convenient modelling and visualisation tool to discover knowledge from modern high-throughput genomics and postgenomics data sets. Indeed, biological entities are not isolated, but are components of complex multi-level systems. We go one step further and advocate for the consideration of causal representations of the interactions in living systems.We present the causal formalism and bring it out in the context of biological networks, when the data is observational. We also discuss its ability to decipher the causal information flow as observed in gene expression. We also illustrate our exploration by experiments on small simulated networks as well as on a real biological data set.

q-bio.QM↗

arXiv2018

Gene regulatory networks: a primer in biological processes and statistical modelling

Modelling gene regulatory networks not only requires a thorough understanding of the biological system depicted but also the ability to accurately represent this system from a mathematical perspective. Throughout this chapter, we aim to familiarise the reader with the biological processes and molecular factors at play in the process of gene expression regulation.We first describe the different interactions controlling each step of the expression process, from transcription to mRNA and protein decay. In the second section, we provide statistical tools to accurately represent this biological complexity in the form of mathematical models. Amongst other considerations, we discuss the topological properties of biological networks, the application of deterministic and stochastic frameworks and the quantitative modelling of regulation. We particularly focus on the use of such models for the simulation of expression data that can serve as a benchmark for the testing of network inference algorithms.

q-bio.QM↗

arXiv2015

Inferring large graphs using l1-penalized likelihood

We address the issue of recovering the structure of large sparse directed acyclic graphs from noisy observations of the system. We propose a novel procedure based on a specific formulation of the l1-norm regularized maximum likelihood, which decomposes the graph estimation into two optimization sub-problems: topological structure and node order learning. We provide oracle inequalities for the graph estimator, as well as an algorithm to solve the induced optimization problem, in the form of a convex program embedded in a genetic algorithm. We apply our method to various data sets (including data from the DREAM4 challenge) and show that it compares favorably to state-of-the-art methods.

math.ST↗

arXiv2015

Exact and approximate inference in graphical models: variable elimination and beyond

Probabilistic graphical models offer a powerful framework to account for the dependence structure between variables, which is represented as a graph. However, the dependence between variables may render inference tasks intractable. In this paper we review techniques exploiting the graph structure for exact inference, borrowed from optimisation and computer science. They are built on the principle of variable elimination whose complexity is dictated in an intricate way by the order in which variables are eliminated. The so-called treewidth of the graph characterises this algorithmic complexity: low-treewidth graphs can be processed efficiently. The first message that we illustrate is therefore the idea that for inference in graphical model, the number of variables is not the limiting factor, and it is worth checking for the treewidth before turning to approximate methods. We show how algorithms providing an upper bound of the treewidth can be exploited to derive a 'good' elimination order enabling to perform exact inference. The second message is that when the treewidth is too large, algorithms for approximate inference linked to the principle of variable elimination, such as loopy belief propagation and variational approaches, can lead to accurate results while being much less time consuming than Monte-Carlo approaches. We illustrate the techniques reviewed in this article on benchmarks of inference problems in genetic linkage analysis and computer vision, as well as on hidden variables restoration in coupled Hidden Markov Models.

stat.ML↗

arXiv2014

Bridging physiological and evolutionary time scales in a gene regulatory network

Gene regulatory networks (GRN) govern phenotypic adaptations and reflect the trade-offs between physiological responses and evolutionary adaptation that act at different time scales. To identify patterns of molecular function and genetic diversity in GRNs, we studied the drought response of the common sunflower, Helianthus annuus, and how the underlying GRN is related to its evolution. We examined the responses of 32,423 expressed sequences to drought and to abscisic acid and selected 145 co-expressed transcripts. We characterized their regulatory relationships in nine kinetic studies based on different hormones. From this, we inferred a GRN by meta-analyses of a Gaussian graphical model and a random forest algorithm and studied the genetic differentiation among populations (FST) at nodes. We identified two main hubs in the network that transport nitrate in guard cells. This suggests that nitrate transport is a critical aspect of sunflower physiological response to drought. We observed that differentiation of the network genes in elite sunflower cultivars is correlated with their position and connectivity. This systems biology approach combined molecular data at different time scales and identified important physiological processes. At the evolutionary level, we propose that network topology could influence responses to human selection and possibly adaptation to dry environments.

q-bio.MN↗