scholarly journals WASABI: a dynamic iterative framework for gene regulatory network inference

2018 ◽  
Author(s):  
Arnaud Bonnaffoux ◽  
Ulysse Herbach ◽  
Angélique Richard ◽  
Anissa Guillemin ◽  
Sandrine Giraud ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Network Inference ◽  
Molecular Mechanisms ◽  
Gene Regulatory Network Inference ◽  
Piecewise Deterministic Markov Processes ◽  
Gene Regulatory ◽  
Cell Data

AbstractInference of gene regulatory networks from gene expression data has been a long-standing and notoriously difficult task in systems biology. Recently, single-cell transcriptomic data have been massively used for gene regulatory network inference, with both successes and limitations. In the present work we propose an iterative algorithm called WASABI, dedicated to inferring a causal dynamical network from time-stamped single-cell data, which tackles some of the limitations associated with current approaches. We first introduce the concept of waves, which posits that the information provided by an external stimulus will affect genes one-by-one through a cascade, like waves spreading through a network. This concept allows us to infer the network one gene at a time, after genes have been ordered regarding their time of regulation. We then demonstrate the ability of WASABI to correctly infer small networks, which have been simulated in silico using a mechanistic model consisting of coupled piecewise-deterministic Markov processes for the proper description of gene expression at the single-cell level. We finally apply WASABI on in vitro generated data on an avian model of erythroid differentiation. The structure of the resulting gene regulatory network sheds a fascinating new light on the molecular mechanisms controlling this process. In particular, we find no evidence for hub genes and a much more distributed network structure than expected. Interestingly, we find that a majority of genes are under the direct control of the differentiation-inducing stimulus. In conclusion, WASABI is a versatile algorithm which should help biologists to fully exploit the power of time-stamped single-cell data.

SIN-KNO: A method of gene regulatory network inference using single-cell transcription and gene knockout data

2019 ◽  
Vol 17 (06) ◽  
pp. 1950035
Author(s):  
Huiqing Wang ◽  
Yuanyuan Lian ◽  
Chun Li ◽  
Yue Ma ◽  
Zhiliang Yan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Single Cell ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Gene Knockout ◽  
Cell Heterogeneity ◽  
State Information ◽  
Gene Regulatory ◽  
Cell Data

As a tool of interpreting and analyzing genetic data, gene regulatory network (GRN) could reveal regulatory relationships between genes, proteins, and small molecules, as well as understand physiological activities and functions within biological cells, interact in pathways, and how to make changes in the organism. Traditional GRN research focuses on the analysis of the regulatory relationships through the average of cellular gene expressions. These methods are difficult to identify the cell heterogeneity of gene expression. Existing methods for inferring GRN using single-cell transcriptional data lack expression information when genes reach steady state, and the high dimensionality of single-cell data leads to high temporal and spatial complexity of the algorithm. In order to solve the problem in traditional GRN inference methods, including the lack of cellular heterogeneity information, single-cell data complexity and lack of steady-state information, we propose a method for GRN inference using single-cell transcription and gene knockout data, called SINgle-cell transcription data-KNOckout data (SIN-KNO), which focuses on combining dynamic and steady-state information of regulatory relationship contained in gene expression. Capturing cell heterogeneity information could help understand the gene expression difference in different cells. So, we could observe gene expression changes more accurately. Gene knockout data could observe the gene expression levels at steady-state of all other genes when one gene is knockout. Classifying the genes before analyzing the single-cell data could determine a large number of non-existent regulation, greatly reducing the number of regulation required for inference. In order to show the efficiency, the proposed method has been compared with several typical methods in this area including GENIE3, JUMP3, and SINCERITIES. The results of the evaluation indicate that the proposed method can analyze the diversified information contained in the two types of data, establish a more accurate gene regulation network, and improve the computational efficiency. The method provides a new thinking for dealing with large datasets and high computational complexity of single-cell data in the GRN inference.

scholarly journals Benchmarking algorithms for gene regulatory network inference from single-cell transcriptomic data

2020 ◽  
Vol 17 (2) ◽  
pp. 147-154 ◽  
Author(s):  
Aditya Pratapa ◽  
Amogh P. Jalihal ◽  
Jeffrey N. Law ◽  
Aditya Bharadwaj ◽  
T. M. Murali
Keyword(s):  
Single Cell ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Network Inference ◽  
Gene Regulatory Network Inference ◽  
Transcriptomic Data ◽  
Gene Regulatory

Inferring Gene Regulatory Networks from Genetical Genomics Data

2010 ◽  
pp. 79-107 ◽  
Author(s):  
Bing Liu ◽  
Ina Hoeschele ◽  
Alberto de la Fuente
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Network Inference ◽  
Dna Marker ◽  
Search Space ◽  
Genetical Genomics ◽  
Gene Regulatory Network Inference ◽  
Gene Regulatory

In this chapter, we review the current state of Gene Regulatory Network inference based on ‘Genetical Genomics’ experiments (Brem & Kruglyak, 2005; Brem, Yvert, Clinton & Kruglyak, 2002; Jansen, 2003; Jansen & Nap, 2001; Schadt et al., 2003) as a special case of causal network inference in ‘Systems Genetics’ (Threadgill, 2006). In a Genetical Genomics experiment, a segregating or genetically randomized population is DNA marker genotyped and gene-expression profiled on a genomewide scale. The genotypes are regarded as natural, multifactorial perturbations resulting in different gene-expression ‘phenotypes’, and causal relationships can therefore be established between the measured genotypes and the gene-expression phenotypes. In this chapter, we review different computational approaches to Gene Regulatory Network inference based on the joint analysis of DNA marker and expression data and additionally of DNA sequence information if available. This includes different methods for expression QTL mapping, selection of regulator-target pairs, construction of an encompassing network, which strongly constrains the network search space, and pairwise and multivariate methods for Gene Regulatory Network inference, such as Bayesian Networks and Structural Equation Modeling.

scholarly journals Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference

2020 ◽  
Vol 21 (21) ◽  
pp. 7886
Author(s):  
Furqan Aziz ◽  
Animesh Acharjee ◽  
John A. Williams ◽  
Dominic Russ ◽  
Laura Bravo-Merodio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Network Inference ◽  
Partial Least Square ◽  
Least Square ◽  
Ductal Adenocarcinoma ◽  
Gene Regulatory Network Inference ◽  
Gene Regulatory ◽  
Regulator Genes

Inferring the topology of a gene regulatory network (GRN) from gene expression data is a challenging but important undertaking for gaining a better understanding of gene regulation. Key challenges include working with noisy data and dealing with a higher number of genes than samples. Although a number of different methods have been proposed to infer the structure of a GRN, there are large discrepancies among the different inference algorithms they adopt, rendering their meaningful comparison challenging. In this study, we used two methods, namely the MIDER (Mutual Information Distance and Entropy Reduction) and the PLSNET (Partial least square based feature selection) methods, to infer the structure of a GRN directly from data and computationally validated our results. Both methods were applied to different gene expression datasets resulting from inflammatory bowel disease (IBD), pancreatic ductal adenocarcinoma (PDAC), and acute myeloid leukaemia (AML) studies. For each case, gene regulators were successfully identified. For example, for the case of the IBD dataset, the UGT1A family genes were identified as key regulators while upon analysing the PDAC dataset, the SULF1 and THBS2 genes were depicted. We further demonstrate that an ensemble-based approach, that combines the output of the MIDER and PLSNET algorithms, can infer the structure of a GRN from data with higher accuracy. We have also estimated the number of the samples required for potential future validation studies. Here, we presented our proposed analysis framework that caters not only to candidate regulator genes prediction for potential validation experiments but also an estimation of the number of samples required for these experiments.

scholarly journals Gene regulatory network inference from single-cell data using multivariate information measures

2016 ◽  
Author(s):  
Thalia E. Chan ◽  
Michael P.H. Stumpf ◽  
Ann C. Babtie
Keyword(s):  
Gene Expression ◽  
Information Theory ◽  
Single Cell ◽  
Network Inference ◽  
Gene Regulatory Network Inference ◽  
Functional Relationships ◽  
Cell Gene Expression ◽  
Gene Regulatory ◽  
Cell Data ◽  
Cell Gene

AbstractWhile single-cell gene expression experiments present new challenges for data processing, the cell-to-cell variability observed also reveals statistical relationships that can be used by information theory. Here, we use multivariate information theory to explore the statistical dependencies between triplets of genes in single-cell gene expression datasets. We develop PIDC, a fast, efficient algorithm that uses partial information decomposition (PID) to identify regulatory relationships between genes. We thoroughly evaluate the performance of our algorithm and demonstrate that the higher order information captured by PIDC allows it to outperform pairwise mutual information-based algorithms when recovering true relationships present in simulated data. We also infer gene regulatory networks from three experimental single-cell data sets and illustrate how network context, choices made during analysis, and sources of variability affect network inference. PIDC tutorials and open-source software for estimating PID are available here:https://github.com/Tchanders/network_inference_tutorials. PIDC should facilitate the identification of putative functional relationships and mechanistic hypotheses from single-cell transcriptomic data.

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