scholarly journals Incomplete graphical model inference via latent tree aggregation

2018 ◽  
Vol 19 (5) ◽  
pp. 545-568 ◽  
Author(s):  
Geneviéve Robin ◽  
Christophe Ambroise ◽  
Stéphane Robin
Keyword(s):  
Graphical Models ◽  
Network Inference ◽  
Spanning Trees ◽  
Graphical Model ◽  
Expectation Maximization Algorithm ◽  
Estimation Procedure ◽  
R Package ◽  
Original Network ◽  
Model Inference ◽  
Missing Variables

Graphical network inference is used in many fields such as genomics or ecology to infer the conditional independence structure between variables, from measurements of gene expression or species abundances for instance. In many practical cases, not all variables involved in the network have been observed, and the samples are actually drawn from a distribution where some variables have been marginalized out. This challenges the sparsity assumption commonly made in graphical model inference, since marginalization yields locally dense structures, even when the original network is sparse. We present a procedure for inferring Gaussian graphical models when some variables are unobserved, that accounts both for the influence of missing variables and the low density of the original network. Our model is based on the aggregation of spanning trees, and the estimation procedure on the expectation-maximization algorithm. We treat the graph structure and the unobserved nodes as missing variables and compute posterior probabilities of edge appearance. To provide a complete methodology, we also propose several model selection criteria to estimate the number of missing nodes. A simulation study and an illustration on flow cytometry data reveal that our method has favourable edge detection properties compared to existing graph inference techniques. The methods are implemented in an R package.

scholarly journals Disentangling microbial associations from hidden environmental and technical factors via latent graphical models

2019 ◽  
Author(s):  
Zachary D. Kurtz ◽  
Richard Bonneau ◽  
Christian L. Müller
Keyword(s):  
Graphical Models ◽  
Graphical Model ◽  
R Package ◽  
Comprehensive Collection ◽  
Performance Guarantees ◽  
Ecological Association ◽  
Microbial Associations ◽  
Sparse Inverse Covariance Estimation ◽  
Statistical Relationships ◽  
And Function

AbstractDetecting community-wide statistical relationships from targeted amplicon-based and metagenomic profiling of microbes in their natural environment is an important step toward understanding the organization and function of these communities. We present a robust and computationally tractable latent graphical model inference scheme that allows simultaneous identification of parsimonious statistical relationships among microbial species and unobserved factors that influence the prevalence and variability of the abundance measurements. Our method comes with theoretical performance guarantees and is available within the SParse InversE Covariance estimation for Ecological ASsociation Inference (SPIEC-EASI) framework (‘SpiecEasi’ R-package). Using simulations, as well as a comprehensive collection of amplicon-based gut microbiome datasets, we illustrate the method’s ability to jointly identify compositional biases, latent factors that correlate with observed technical covariates, and robust statistical microbial associations that replicate across different gut microbial data sets.

scholarly journals NEM-Tar: A Probabilistic Graphical Model for Cancer Regulatory Network Inference and Prioritization of Potential Therapeutic Targets From Multi-Omics Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuchen Zhang ◽  
Lina Zhu ◽  
Xin Wang
Keyword(s):  
Graphical Models ◽  
Drug Targets ◽  
Network Inference ◽  
Graphical Model ◽  
Information Gain ◽  
Therapeutic Targets ◽  
Hill Climbing ◽  
Omics Data ◽  
Pathway Inference ◽  
The Impact

Targeted therapy has been widely adopted as an effective treatment strategy to battle against cancer. However, cancers are not single disease entities, but comprising multiple molecularly distinct subtypes, and the heterogeneity nature prevents precise selection of patients for optimized therapy. Dissecting cancer subtype-specific signaling pathways is crucial to pinpointing dysregulated genes for the prioritization of novel therapeutic targets. Nested effects models (NEMs) are a group of graphical models that encode subset relations between observed downstream effects under perturbations to upstream signaling genes, providing a prototype for mapping the inner workings of the cell. In this study, we developed NEM-Tar, which extends the original NEMs to predict drug targets by incorporating causal information of (epi)genetic aberrations for signaling pathway inference. An information theory-based score, weighted information gain (WIG), was proposed to assess the impact of signaling genes on a specific downstream biological process of interest. Subsequently, we conducted simulation studies to compare three inference methods and found that the greedy hill-climbing algorithm demonstrated the highest accuracy and robustness to noise. Furthermore, two case studies were conducted using multi-omics data for colorectal cancer (CRC) and gastric cancer (GC) in the TCGA database. Using NEM-Tar, we inferred signaling networks driving the poor-prognosis subtypes of CRC and GC, respectively. Our model prioritized not only potential individual drug targets such as HER2, for which FDA-approved inhibitors are available but also the combinations of multiple targets potentially useful for the design of combination therapies.

scholarly journals Tailored graphical lasso for data integration in gene network reconstruction

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Camilla Lingjærde ◽  
Tonje G. Lien ◽  
Ørnulf Borgan ◽  
Helga Bergholtz ◽  
Ingrid K. Glad
Keyword(s):  
Biological Networks ◽  
Prior Information ◽  
Network Inference ◽  
Graphical Model ◽  
Network Models ◽  
R Package ◽  
Biological Information ◽  
Graphical Lasso ◽  
Special Cases ◽  
The Matrix

Abstract Background Identifying gene interactions is a topic of great importance in genomics, and approaches based on network models provide a powerful tool for studying these. Assuming a Gaussian graphical model, a gene association network may be estimated from multiomic data based on the non-zero entries of the inverse covariance matrix. Inferring such biological networks is challenging because of the high dimensionality of the problem, making traditional estimators unsuitable. The graphical lasso is constructed for the estimation of sparse inverse covariance matrices in such situations, using $$L_1$$ L 1 -penalization on the matrix entries. The weighted graphical lasso is an extension in which prior biological information from other sources is integrated into the model. There are however issues with this approach, as it naïvely forces the prior information into the network estimation, even if it is misleading or does not agree with the data at hand. Further, if an associated network based on other data is used as the prior, the method often fails to utilize the information effectively. Results We propose a novel graphical lasso approach, the tailored graphical lasso, that aims to handle prior information of unknown accuracy more effectively. We provide an R package implementing the method, . Applying the method to both simulated and real multiomic data sets, we find that it outperforms the unweighted and weighted graphical lasso in terms of all performance measures we consider. In fact, the graphical lasso and weighted graphical lasso can be considered special cases of the tailored graphical lasso, and a parameter determined by the data measures the usefulness of the prior information. We also find that among a larger set of methods, the tailored graphical is the most suitable for network inference from high-dimensional data with prior information of unknown accuracy. With our method, mRNA data are demonstrated to provide highly useful prior information for protein–protein interaction networks. Conclusions The method we introduce utilizes useful prior information more effectively without involving any risk of loss of accuracy should the prior information be misleading.

scholarly journals Tailored Graphical Lasso for Data Integration in Gene Network Reconstruction

2020 ◽  
Author(s):  
Camilla Lingjærde ◽  
Tonje G Lien ◽  
Ørnulf Borgan ◽  
Ingrid K Glad
Keyword(s):  
Graphical Models ◽  
Biological Networks ◽  
Prior Information ◽  
Graphical Model ◽  
Network Models ◽  
R Package ◽  
Biological Information ◽  
Graphical Lasso ◽  
Special Cases ◽  
The Matrix

AbstractBackgroundIdentifying gene interactions is a topic of great importance in genomics, and approaches based on network models provide a powerful tool for studying these. Assuming a Gaussian graphical model, a gene association network may be estimated from multiomic data based on the non-zero entries of the inverse covariance matrix. Inferring such biological networks is challenging because of the high dimensionality of the problem, making traditional estimators unsuitable. The graphical lasso is constructed for the estimation of sparse inverse covariance matrices in Gaussian graphical models in such situations, using L1-penalization on the matrix entries. An extension of the graphical lasso is the weighted graphical lasso, in which prior biological information from other (data) sources is integrated into the model through the weights. There are however issues with this approach, as it naïvely forces the prior information into the network estimation, even if it is misleading or does not agree with the data at hand. Further, if an associated network based on other data is used as the prior, weighted graphical lasso often fails to utilize the information effectively.ResultsWe propose a novel graphical lasso approach, the tailored graphical lasso, that aims to handle prior information of unknown accuracy more effectively. We provide an R package implementing the method, tailoredGlasso. Applying the method to both simulated and real multiomic data sets, we find that it outperforms the unweighted and weighted graphical lasso in terms of all performance measures we consider. In fact, the graphical lasso and weighted graphical lasso can be considered special cases of the tailored graphical lasso, and a parameter determined by the data measures the usefulness of the prior information. With our method, mRNA data are demonstrated to provide highly useful prior information for protein-protein interaction networks.ConclusionsThe method we introduce utilizes useful prior information more effectively without involving any risk of loss of accuracy should the prior information be misleading.

scholarly journals Estimating Differential Latent Variable Graphical Models with Applications to Brain Connectivity

Biometrika ◽  
2020 ◽  
Author(s):  
S Na ◽  
M Kolar ◽  
O Koyejo
Keyword(s):  
Graphical Models ◽  
Latent Variable ◽  
Graphical Model ◽  
Brain Connectivity ◽  
Statistical Error ◽  
Real Data ◽  
Low Rank ◽  
Conditional Dependence ◽  
Gradient Descent Algorithm ◽  
The Difference

Abstract Differential graphical models are designed to represent the difference between the conditional dependence structures of two groups, thus are of particular interest for scientific investigation. Motivated by modern applications, this manuscript considers an extended setting where each group is generated by a latent variable Gaussian graphical model. Due to the existence of latent factors, the differential network is decomposed into sparse and low-rank components, both of which are symmetric indefinite matrices. We estimate these two components simultaneously using a two-stage procedure: (i) an initialization stage, which computes a simple, consistent estimator, and (ii) a convergence stage, implemented using a projected alternating gradient descent algorithm applied to a nonconvex objective, initialized using the output of the first stage. We prove that given the initialization, the estimator converges linearly with a nontrivial, minimax optimal statistical error. Experiments on synthetic and real data illustrate that the proposed nonconvex procedure outperforms existing methods.

scholarly journals Functional connectomics from neural dynamics: probabilistic graphical models for neuronal network of Caenorhabditis elegans

2018 ◽  
Vol 373 (1758) ◽  
pp. 20170377 ◽  
Author(s):  
Hexuan Liu ◽  
Jimin Kim ◽  
Eli Shlizerman
Keyword(s):  
Time Series ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Graphical Models ◽  
Neuronal Network ◽  
Graphical Model ◽  
Time Series Data ◽  
Series Data ◽  
Neuronal Responses ◽  
C Elegans

We propose an approach to represent neuronal network dynamics as a probabilistic graphical model (PGM). To construct the PGM, we collect time series of neuronal responses produced by the neuronal network and use singular value decomposition to obtain a low-dimensional projection of the time-series data. We then extract dominant patterns from the projections to get pairwise dependency information and create a graphical model for the full network. The outcome model is a functional connectome that captures how stimuli propagate through the network and thus represents causal dependencies between neurons and stimuli. We apply our methodology to a model of the Caenorhabditis elegans somatic nervous system to validate and show an example of our approach. The structure and dynamics of the C. elegans nervous system are well studied and a model that generates neuronal responses is available. The resulting PGM enables us to obtain and verify underlying neuronal pathways for known behavioural scenarios and detect possible pathways for novel scenarios. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

scholarly journals MSCquartets 1.0: Quartet methods for species trees and networks under the multispecies coalescent model in R

2020 ◽  
Author(s):  
John A Rhodes ◽  
Hector Baños ◽  
Jonathan D Mitchell ◽  
Elizabeth S Allman
Keyword(s):  
Network Inference ◽  
Incomplete Lineage Sorting ◽  
R Package ◽  
Species Tree ◽  
Supplementary Information ◽  
Species Trees ◽  
Lineage Sorting ◽  
Coalescent Model ◽  
Multispecies Coalescent ◽  
Tree Inference

Abstract Summary MSCquartets is an R package for species tree hypothesis testing, inference of species trees, and inference of species networks under the Multispecies Coalescent model of incomplete lineage sorting and its network analog. Input for these analyses are collections of metric or topological locus trees which are then summarized by the quartets displayed on them. Results of hypothesis tests at user-supplied levels are displayed in a simplex plot by color-coded points. The package implements the QDC and WQDC algorithms for topological and metric species tree inference, and the NANUQ algorithm for level-1 topological species network inference, all of which give statistically consistent estimators under the model. Availability MSCquartets is available through the Comprehensive R Archive Network: https://CRAN.R-project.org/package=MSCquartets. Supplementary information Supplementary materials, including example data and analyses, are incorporated into the package.

scholarly journals Collaborative Intelligence: Accelerating Deep Neural Network Inference via Device-Edge Synergy

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nanliang Shan ◽  
Zecong Ye ◽  
Xiaolong Cui
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Deep Neural Network ◽  
Network Inference ◽  
Partition Scheme ◽  
Model Inference ◽  
Cloud Server ◽  
Hardware Configuration ◽  
Collaborative Intelligence ◽  
Service Latency

With the development of mobile edge computing (MEC), more and more intelligent services and applications based on deep neural networks are deployed on mobile devices to meet the diverse and personalized needs of users. Unfortunately, deploying and inferencing deep learning models on resource-constrained devices are challenging. The traditional cloud-based method usually runs the deep learning model on the cloud server. Since a large amount of input data needs to be transmitted to the server through WAN, it will cause a large service latency. This is unacceptable for most current latency-sensitive and computation-intensive applications. In this paper, we propose Cogent, an execution framework that accelerates deep neural network inference through device-edge synergy. In the Cogent framework, it is divided into two operation stages, including the automatic pruning and partition stage and the containerized deployment stage. Cogent uses reinforcement learning (RL) to automatically predict pruning and partition strategies based on feedback from the hardware configuration and system conditions so that the pruned and partitioned model can better adapt to the system environment and user hardware configuration. Then through containerized deployment to the device and the edge server to accelerate model inference, experiments show that the learning-based hardware-aware automatic pruning and partition scheme can significantly reduce the service latency, and it accelerates the overall model inference process while maintaining accuracy. Using this method can accelerate up to 8.89× without loss of accuracy of more than 7%.

DiffNetFDR: differential network analysis with false discovery rate control

2019 ◽  
Vol 35 (17) ◽  
pp. 3184-3186
Author(s):  
Xiao-Fei Zhang ◽  
Le Ou-Yang ◽  
Shuo Yang ◽  
Xiaohua Hu ◽  
Hong Yan
Keyword(s):  
False Discovery Rate ◽  
Graphical Models ◽  
Biological Significance ◽  
R Package ◽  
Supplementary Information ◽  
Gaussian Graphical Models ◽  
Multiple Testing Procedure ◽  
False Discovery ◽  
Differential Network ◽  
Shiny App

Abstract Summary To identify biological network rewiring under different conditions, we develop a user-friendly R package, named DiffNetFDR, to implement two methods developed for testing the difference in different Gaussian graphical models. Compared to existing tools, our methods have the following features: (i) they are based on Gaussian graphical models which can capture the changes of conditional dependencies; (ii) they determine the tuning parameters in a data-driven manner; (iii) they take a multiple testing procedure to control the overall false discovery rate; and (iv) our approach defines the differential network based on partial correlation coefficients so that the spurious differential edges caused by the variants of conditional variances can be excluded. We also develop a Shiny application to provide easier analysis and visualization. Simulation studies are conducted to evaluate the performance of our methods. We also apply our methods to two real gene expression datasets. The effectiveness of our methods is validated by the biological significance of the identified differential networks. Availability and implementation R package and Shiny app are available at https://github.com/Zhangxf-ccnu/DiffNetFDR. Supplementary information Supplementary data are available at Bioinformatics online.

Sign in / Sign up

Export Citation Format

Share Document