Dataset Information

Probabilistic edge inference of gene networks with markov random field-based bayesian learning.

ABSTRACT: Current algorithms for gene regulatory network construction based on Gaussian graphical models focuses on the deterministic decision of whether an edge exists. Both the probabilistic inference of edge existence and the relative strength of edges are often overlooked, either because the computational algorithms cannot account for this uncertainty or because it is not straightforward in implementation. In this study, we combine the Bayesian Markov random field and the conditional autoregressive (CAR) model to tackle simultaneously these two tasks. The uncertainty of edge existence and the relative strength of edges can be measured and quantified based on a Bayesian model such as the CAR model and the spike-and-slab lasso prior. In addition, the strength of the edges can be utilized to prioritize the importance of the edges in a network graph. Simulations and a glioblastoma cancer study were carried out to assess the proposed model's performance and to compare it with existing methods when a binary decision is of interest. The proposed approach shows stable performance and may provide novel structures with biological insights.

SUBMITTER: Huang YJ

PROVIDER: S-EPMC9684306 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Probabilistic edge inference of gene networks with markov random field-based bayesian learning.

Huang Yu-Jyun YJ Mukherjee Rajarshi R Hsiao Chuhsing Kate CK

Frontiers in genetics 20221110

Current algorithms for gene regulatory network construction based on Gaussian graphical models focuses on the deterministic decision of whether an edge exists. Both the probabilistic inference of edge existence and the relative strength of edges are often overlooked, either because the computational algorithms cannot account for this uncertainty or because it is not straightforward in implementation. In this study, we combine the Bayesian Markov random field and the conditional autoregressive (C ...[more]

PMID: 36437931

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Project description:BackgroundRecent advances in sequencing technologies have enabled parallel assays of chromatin accessibility and gene expression for major human cell lines. Such innovation provides a great opportunity to decode phenotypic consequences of genetic variation via the construction of predictive gene regulatory network models. However, there still lacks a computational method to systematically integrate chromatin accessibility information with gene expression data to recover complicated regulatory relationships between genes in a tissue-specific manner.ResultsWe propose a Markov random field (MRF) model for constructing tissue-specific transcriptional regulatory networks via integrative analysis of DNase-seq and RNA-seq data. Our method, named CSNets (cell-line specific regulatory networks), first infers regulatory networks for individual cell lines using chromatin accessibility information, and then fine-tunes these networks using the MRF based on pairwise similarity between cell lines derived from gene expression data. Using this method, we constructed regulatory networks specific to 110 human cell lines and 13 major tissues with the use of ENCODE data. We demonstrated the high quality of these networks via comprehensive statistical analysis based on ChIP-seq profiles, functional annotations, taxonomic analysis, and literature surveys. We further applied these networks to analyze GWAS data of Crohn's disease and prostate cancer. Results were either consistent with the literature or provided biological insights into regulatory mechanisms of these two complex diseases. The website of CSNets is freely available at http://bioinfo.au.tsinghua.edu.cn/jianglab/CSNETS/ .ConclusionsCSNets demonstrated the power of joint analysis on epigenomic and transcriptomic data towards the accurate construction of gene regulatory network. Our work provides not only a useful resource of regulatory networks to the community, but also valuable experiences in methodology development for multi-omics data integration.

Project description:BackgroundInference of gene networks typically relies on measurements across a wide range of conditions or treatments. Although one network structure is predicted, the relationship between genes could vary across conditions. A comprehensive approach to infer general and condition-dependent gene networks was evaluated. This approach integrated Bayesian network and Gaussian mixture models to describe continuous microarray gene expression measurements, and three gene networks were predicted.ResultsThe first reconstructions of a circadian rhythm pathway in honey bees and an adherens junction pathway in mouse embryos were obtained. In addition, general and condition-specific gene relationships, some unexpected, were detected in these two pathways and in a yeast cell-cycle pathway. The mixture Bayesian network approach identified all (honey bee circadian rhythm and mouse adherens junction pathways) or the vast majority (yeast cell-cycle pathway) of the gene relationships reported in empirical studies. Findings across the three pathways and data sets indicate that the mixture Bayesian network approach is well-suited to infer gene pathways based on microarray data. Furthermore, the interpretation of model estimates provided a broader understanding of the relationships between genes. The mixture models offered a comprehensive description of the relationships among genes in complex biological processes or across a wide range of conditions. The mixture parameter estimates and corresponding odds that the gene network inferred for a sample pertained to each mixture component allowed the uncovering of both general and condition-dependent gene relationships and patterns of expression.ConclusionThis study demonstrated the two main benefits of learning gene pathways using mixture Bayesian networks. First, the identification of the optimal number of mixture components supported by the data offered a robust approach to infer gene relationships and estimate gene expression profiles. Second, the classification of conditions and observations into groups that support particular mixture components helped to uncover both gene relationships that are unique or common across conditions. Results from the application of mixture Bayesian networks substantially augmented the understanding of gene networks and demonstrated the added-value of this methodology to infer gene networks.

Dataset Information

Probabilistic edge inference of gene networks with markov random field-based bayesian learning.

Publications

Probabilistic edge inference of gene networks with markov random field-based bayesian learning.

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