Mathematical modelling plant signalling networks

During the last two decades, molecular genetic studies and the completion of the sequencing of the Arabidopsis thaliana genome have increased knowledge of hormonal regulation in plants. These signal transduction pathways act in concert through gene regulatory and signalling networks whose main components have begun to be elucidated. Our understanding of the resulting cellular processes is hindered by the complex, and sometimes counter-intuitive, dynamics of the networks, which may be interconnected through feedback controls and cross-regulation. Mathematical modelling provides a valuable tool to investigate such dynamics and to perform in silico experiments that may not be easily carried out in a laboratory. In this article, we firstly review general methods for modelling gene and signalling networks and their application in plants. We then describe specific models of hormonal perception and cross-talk in plants. This sub-cellular analysis paves the way for more comprehensive mathematical studies of hormonal transport and signalling in a multi-scale setting

netgwas: An R Package for Network-Based Genome-Wide Association Studies

Graphical models are powerful tools for modeling and making statistical inferences regarding complex associations among variables in multivariate data. In this paper we introduce the R package netgwas, which is designed based on undirected graphical models to accomplish three important and interrelated goals in genetics: constructing linkage map, reconstructing linkage disequilibrium (LD) networks from multi-loci genotype data, and detecting high-dimensional genotype-phenotype networks. The netgwas package deals with species with any chromosome copy number in a unified way, unlike other software. It implements recent improvements in both linkage map construction (Behrouzi and Wit, 2018), and reconstructing conditional independence network for non-Gaussian continuous data, discrete data, and mixed discrete-and-continuous data (Behrouzi and Wit, 2017). Such datasets routinely occur in genetics and genomics such as genotype data, and genotype-phenotype data. We demonstrate the value of our package functionality by applying it to various multivariate example datasets taken from the literature. We show, in particular, that our package allows a more realistic analysis of data, as it adjusts for the effect of all other variables while performing pairwise associations. This feature controls for spurious associations between variables that can arise from classical multiple testing approach. This paper includes a brief overview of the statistical methods which have been implemented in the package. The main body of the paper explains how to use the package. The package uses a parallelization strategy on multi-core processors to speed-up computations for large datasets. In addition, it contains several functions for simulation and visualization. The netgwas package is freely available at https://cran.r-project.org/web/packages/netgwasComment: 32 pages, 9 figures; due to the limitation "The abstract field cannot be longer than 1,920 characters", the abstract appearing here is slightly shorter than that in the PDF fil

Stochastic reaction networks with input processes: Analysis and applications to reporter gene systems

Stochastic reaction network models are widely utilized in biology and chemistry to describe the probabilistic dynamics of biochemical systems in general, and gene interaction networks in particular. Most often, statistical analysis and inference of these systems is addressed by parametric approaches, where the laws governing exogenous input processes, if present, are themselves fixed in advance. Motivated by reporter gene systems, widely utilized in biology to monitor gene activation at the individual cell level, we address the analysis of reaction networks with state-affine reaction rates and arbitrary input processes. We derive a generalization of the so-called moment equations where the dynamics of the network statistics are expressed as a function of the input process statistics. In stationary conditions, we provide a spectral analysis of the system and elaborate on connections with linear filtering. We then apply the theoretical results to develop a method for the reconstruction of input process statistics, namely the gene activation autocovariance function, from reporter gene population snapshot data, and demonstrate its performance on a simulated case study

Hybrid Collaborative Filtering with Autoencoders

Collaborative Filtering aims at exploiting the feedback of users to provide personalised recommendations. Such algorithms look for latent variables in a large sparse matrix of ratings. They can be enhanced by adding side information to tackle the well-known cold start problem. While Neu-ral Networks have tremendous success in image and speech recognition, they have received less attention in Collaborative Filtering. This is all the more surprising that Neural Networks are able to discover latent variables in large and heterogeneous datasets. In this paper, we introduce a Collaborative Filtering Neural network architecture aka CFN which computes a non-linear Matrix Factorization from sparse rating inputs and side information. We show experimentally on the MovieLens and Douban dataset that CFN outper-forms the state of the art and benefits from side information. We provide an implementation of the algorithm as a reusable plugin for Torch, a popular Neural Network framework

Data based identification and prediction of nonlinear and complex dynamical systems

We thank Dr. R. Yang (formerly at ASU), Dr. R.-Q. Su (formerly at ASU), and Mr. Zhesi Shen for their contributions to a number of original papers on which this Review is partly based. This work was supported by ARO under Grant No. W911NF-14-1-0504. W.-X. Wang was also supported by NSFC under Grants No. 61573064 and No. 61074116, as well as by the Fundamental Research Funds for the Central Universities, Beijing Nova Programme.Peer reviewedPostprin

Inferring Regulatory Networks by Combining Perturbation Screens and Steady State Gene Expression Profiles

Reconstructing transcriptional regulatory networks is an important task in functional genomics. Data obtained from experiments that perturb genes by knockouts or RNA interference contain useful information for addressing this reconstruction problem. However, such data can be limited in size and/or are expensive to acquire. On the other hand, observational data of the organism in steady state (e.g. wild-type) are more readily available, but their informational content is inadequate for the task at hand. We develop a computational approach to appropriately utilize both data sources for estimating a regulatory network. The proposed approach is based on a three-step algorithm to estimate the underlying directed but cyclic network, that uses as input both perturbation screens and steady state gene expression data. In the first step, the algorithm determines causal orderings of the genes that are consistent with the perturbation data, by combining an exhaustive search method with a fast heuristic that in turn couples a Monte Carlo technique with a fast search algorithm. In the second step, for each obtained causal ordering, a regulatory network is estimated using a penalized likelihood based method, while in the third step a consensus network is constructed from the highest scored ones. Extensive computational experiments show that the algorithm performs well in reconstructing the underlying network and clearly outperforms competing approaches that rely only on a single data source. Further, it is established that the algorithm produces a consistent estimate of the regulatory network.Comment: 24 pages, 4 figures, 6 table

Inference of the genetic network regulating lateral root initiation in Arabidopsis thaliana

Regulation of gene expression is crucial for organism growth, and it is one of the challenges in Systems Biology to reconstruct the underlying regulatory biological networks from transcriptomic data. The formation of lateral roots in Arabidopsis thaliana is stimulated by a cascade of regulators of which only the interactions of its initial elements have been identified. Using simulated gene expression data with known network topology, we compare the performance of inference algorithms, based on different approaches, for which ready-to-use software is available. We show that their performance improves with the network size and the inclusion of mutants. We then analyse two sets of genes, whose activity is likely to be relevant to lateral root initiation in Arabidopsis, by integrating sequence analysis with the intersection of the results of the best performing methods on time series and mutants to infer their regulatory network. The methods applied capture known interactions between genes that are candidate regulators at early stages of development. The network inferred from genes significantly expressed during lateral root formation exhibits distinct scale-free, small world and hierarchical properties and the nodes with a high out-degree may warrant further investigation

Robust Multi-Objective Sustainable Reverse Supply Chain Planning: An Application in the Steel Industry

In the design of the supply chain, the use of the returned products and their recycling in the production and consumption network is called reverse logistics. The proposed model aims to optimize the flow of materials in the supply chain network (SCN), and determine the amount and location of facilities and the planning of transportation in conditions of demand uncertainty. Thus, maximizing the total profit of operation, minimizing adverse environmental effects, and maximizing customer and supplier service levels have been considered as the main objectives. Accordingly, finding symmetry (balance) among the profit of operation, the environmental effects and customer and supplier service levels is considered in this research. To deal with the uncertainty of the model, scenario-based robust planning is employed alongside a meta-heuristic algorithm (NSGA-II) to solve the model with actual data from a case study of the steel industry in Iran. The results obtained from the model, solving and validating, compared with actual data indicated that the model could optimize the objectives seamlessly and determine the amount and location of the necessary facilities for the steel industry more appropriately.This article belongs to the Special Issue Uncertain Multi-Criteria Optimization Problem

Computational Cancer Biology: An Evolutionary Perspective

ISSN:1553-734XISSN:1553-735