IRIS: a method for reverse engineering of regulatory relations in gene networks

<p>Abstract</p> <p>Background</p> <p>The ultimate aim of systems biology is to understand and describe how molecular components interact to manifest collective behaviour that is the sum of the single parts. Building a network of molecular interactions is the basic step in modelling a complex entity such as the cell. Even if gene-gene interactions only partially describe real networks because of post-transcriptional modifications and protein regulation, using microarray technology it is possible to combine measurements for thousands of genes into a single analysis step that provides a picture of the cell's gene expression. Several databases provide information about known molecular interactions and various methods have been developed to infer gene networks from expression data. However, network topology alone is not enough to perform simulations and predictions of how a molecular system will respond to perturbations. Rules for interactions among the single parts are needed for a complete definition of the network behaviour. Another interesting question is how to integrate information carried by the network topology, which can be derived from the literature, with large-scale experimental data.</p> <p>Results</p> <p>Here we propose an algorithm, called inference of regulatory interaction schema (IRIS), that uses an iterative approach to map gene expression profile values (both steady-state and time-course) into discrete states and a simple probabilistic method to infer the regulatory functions of the network. These interaction rules are integrated into a factor graph model. We test IRIS on two synthetic networks to determine its accuracy and compare it to other methods. We also apply IRIS to gene expression microarray data for the <it>Saccharomyces cerevisiae </it>cell cycle and for human B-cells and compare the results to literature findings.</p> <p>Conclusions</p> <p>IRIS is a rapid and efficient tool for the inference of regulatory relations in gene networks. A topological description of the network and a matrix of gene expression profiles are required as input to the algorithm. IRIS maps gene expression data onto discrete values and then computes regulatory functions as conditional probability tables. The suitability of the method is demonstrated for synthetic data and microarray data. The resulting network can also be embedded in a factor graph model.</p

Answering queries in hybrid Bayesian networks using importance sampling

In this paper we propose an algorithm for answering queries in hybrid Bayesian networks where the underlying probability distribution is of class MTE (mixture of truncated exponentials). The algorithm is based on importance sampling simulation. We show how, like existing importance sampling algorithms for discrete networks, it is able to provide answers to multiple queries simultaneously using a single sample. The behaviour of the new algorithm is experimentally tested and compared with previous methods existing in the literature

Open problems in causal structure learning: A case study of COVID-19 in the UK

Causal machine learning (ML) algorithms recover graphical structures that tell us something about cause-and-effect relationships. The causal representation praovided by these algorithms enables transparency and explainability, which is necessary for decision making in critical real-world problems. Yet, causal ML has had limited impact in practice compared to associational ML. This paper investigates the challenges of causal ML with application to COVID-19 UK pandemic data. We collate data from various public sources and investigate what the various structure learning algorithms learn from these data. We explore the impact of different data formats on algorithms spanning different classes of learning, and assess the results produced by each algorithm, and groups of algorithms, in terms of graphical structure, model dimensionality, sensitivity analysis, confounding variables, predictive and interventional inference. We use these results to highlight open problems in causal structure learning and directions for future research. To facilitate future work, we make all graphs, models, data sets, and source code publicly available online

Generic Bayesian network models for making maintenance decisions from available data and expert knowledge

To maximise asset reliability cost-effectively, maintenance should be scheduled based on the likely deterioration of an asset. Various statistical models have been proposed for predicting this, but they have important practical limitations. We present a Bayesian network model that can be used for maintenance decision support to overcome these limitations. The model extends an existing statistical model of asset deterioration, but shows how (1) data on the condition of assets available from their periodic inspection can be used, (2) failure data from related groups of asset can be combined using judgement from experts and (3) expert knowledge of the deterioration’s causes can be combined with statistical data to adjust predictions. A case study of bridges on the rail network in Great Britain (GB) is presented, showing how the model could be used for the maintenance decision problem, given typical data likely to be available in practice

Bayesian networks for spatio-temporal integrated catchment assessment

Includes abstract.Includes bibliographical references (leaves 181-203).In this thesis, a methodology for integrated catchment water resources assessment using Bayesian Networks was developed. A custom made software application that combines Bayesian Networks with GIS was used to facilitate data pre-processing and spatial modelling. Dynamic Bayesian Networks were implemented in the software for time-series modelling

A Review of Inference Algorithms for Hybrid Bayesian Networks

Hybrid Bayesian networks have received an increasing attention during the last years. The difference with respect to standard Bayesian networks is that they can host discrete and continuous variables simultaneously, which extends the applicability of the Bayesian network framework in general. However, this extra feature also comes at a cost: inference in these types of models is computationally more challenging and the underlying models and updating procedures may not even support closed-form solutions. In this paper we provide an overview of the main trends and principled approaches for performing inference in hybrid Bayesian networks. The methods covered in the paper are organized and discussed according to their methodological basis. We consider how the methods have been extended and adapted to also include (hybrid) dynamic Bayesian networks, and we end with an overview of established software systems supporting inference in these types of models

MCMC inference for Markov Jump Processes via the Linear Noise Approximation

Bayesian analysis for Markov jump processes is a non-trivial and challenging problem. Although exact inference is theoretically possible, it is computationally demanding thus its applicability is limited to a small class of problems. In this paper we describe the application of Riemann manifold MCMC methods using an approximation to the likelihood of the Markov jump process which is valid when the system modelled is near its thermodynamic limit. The proposed approach is both statistically and computationally efficient while the convergence rate and mixing of the chains allows for fast MCMC inference. The methodology is evaluated using numerical simulations on two problems from chemical kinetics and one from systems biology

Learning Bayesian network equivalence classes using ant colony optimisation

Bayesian networks have become an indispensable tool in the modelling of uncertain knowledge. Conceptually, they consist of two parts: a directed acyclic graph called the structure, and conditional probability distributions attached to each node known as the parameters. As a result of their expressiveness, understandability and rigorous mathematical basis, Bayesian networks have become one of the first methods investigated, when faced with an uncertain problem domain. However, a recurring problem persists in specifying a Bayesian network. Both the structure and parameters can be difficult for experts to conceive, especially if their knowledge is tacit.To counteract these problems, research has been ongoing, on learning both the structure and parameters of Bayesian networks from data. Whilst there are simple methods for learning the parameters, learning the structure has proved harder. Part ofthis stems from the NP-hardness of the problem and the super-exponential space of possible structures. To help solve this task, this thesis seeks to employ a relatively new technique, that has had much success in tackling NP-hard problems. This technique is called ant colony optimisation. Ant colony optimisation is a metaheuristic based on the behaviour of ants acting together in a colony. It uses the stochastic activity of artificial ants to find good solutions to combinatorial optimisation problems. In the current work, this method is applied to the problem of searching through the space of equivalence classes of Bayesian networks, in order to find a good match against a set of data. The system uses operators that evaluate potential modifications to a current state. Each of the modifications is scored and the results used to inform the search. In order to facilitate these steps, other techniques are also devised, to speed up the learning process. The techniques includeThe techniques are tested by sampling data from gold standard networks and learning structures from this sampled data. These structures are analysed using various goodnessof-fit measures to see how well the algorithms perform. The measures include structural similarity metrics and Bayesian scoring metrics. The results are compared in depth against systems that also use ant colony optimisation and other methods, including evolutionary programming and greedy heuristics. Also, comparisons are made to well known state-of-the-art algorithms and a study performed on a real-life data set. The results show favourable performance compared to the other methods and on modelling the real-life data