Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Exploiting network topology for large-scale inference of nonlinear reaction models.

ABSTRACT: The development of chemical reaction models aids understanding and prediction in areas ranging from biology to electrochemistry and combustion. A systematic approach to building reaction network models uses observational data not only to estimate unknown parameters but also to learn model structure. Bayesian inference provides a natural approach to this data-driven construction of models. Yet traditional Bayesian model inference methodologies that numerically evaluate the evidence for each model are often infeasible for nonlinear reaction network inference, as the number of plausible models can be combinatorially large. Alternative approaches based on model-space sampling can enable large-scale network inference, but their realization presents many challenges. In this paper, we present new computational methods that make large-scale nonlinear network inference tractable. First, we exploit the topology of networks describing potential interactions among chemical species to design improved 'between-model' proposals for reversible-jump Markov chain Monte Carlo. Second, we introduce a sensitivity-based determination of move types which, when combined with network-aware proposals, yields significant additional gains in sampling performance. These algorithms are demonstrated on inference problems drawn from systems biology, with nonlinear differential equation models of species interactions.

SUBMITTER: Galagali N

PROVIDER: S-EPMC6451393 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

RANK: Large-Scale Inference with Graphical Nonlinear Knockoffs.

Project description:Power and reproducibility are key to enabling refined scientific discoveries in contemporary big data applications with general high-dimensional nonlinear models. In this paper, we provide theoretical foundations on the power and robustness for the model-X knockoffs procedure introduced recently in Candès, Fan, Janson and Lv (2018) in high-dimensional setting when the covariate distribution is characterized by Gaussian graphical model. We establish that under mild regularity conditions, the power of the oracle knockoffs procedure with known covariate distribution in high-dimensional linear models is asymptotically one as sample size goes to infinity. When moving away from the ideal case, we suggest the modified model-X knockoffs method called graphical nonlin-ear knockoffs (RANK) to accommodate the unknown covariate distribution. We provide theoretical justifications on the robustness of our modified procedure by showing that the false discovery rate (FDR) is asymptotically controlled at the target level and the power is asymptotically one with the estimated covariate distribution. To the best of our knowledge, this is the first formal theoretical result on the power for the knockoffs procedure. Simulation results demonstrate that compared to existing approaches, our method performs competitively in both FDR control and power. A real data set is analyzed to further assess the performance of the suggested knockoffs procedure.

| S-EPMC7394464 | biostudies-literature

Bagging statistical network inference from large-scale gene expression data.

Project description:Modern biology and medicine aim at hunting molecular and cellular causes of biological functions and diseases. Gene regulatory networks (GRN) inferred from gene expression data are considered an important aid for this research by providing a map of molecular interactions. Hence, GRNs have the potential enabling and enhancing basic as well as applied research in the life sciences. In this paper, we introduce a new method called BC3NET for inferring causal gene regulatory networks from large-scale gene expression data. BC3NET is an ensemble method that is based on bagging the C3NET algorithm, which means it corresponds to a Bayesian approach with noninformative priors. In this study we demonstrate for a variety of simulated and biological gene expression data from S. cerevisiae that BC3NET is an important enhancement over other inference methods that is capable of capturing biochemical interactions from transcription regulation and protein-protein interaction sensibly. An implementation of BC3NET is freely available as an R package from the CRAN repository.

| S-EPMC3316596 | biostudies-literature

Oscillations and synchrony in large-scale cortical network models.

Project description:Intrinsic neuronal and circuit properties control the responses of large ensembles of neurons by creating spatiotemporal patterns of activity that are used for sensory processing, memory formation, and other cognitive tasks. The modeling of such systems requires computationally efficient single-neuron models capable of displaying realistic response properties. We developed a set of reduced models based on difference equations (map-based models) to simulate the intrinsic dynamics of biological neurons. These phenomenological models were designed to capture the main response properties of specific types of neurons while ensuring realistic model behavior across a sufficient dynamic range of inputs. This approach allows for fast simulations and efficient parameter space analysis of networks containing hundreds of thousands of neurons of different types using a conventional workstation. Drawing on results obtained using large-scale networks of map-based neurons, we discuss spatiotemporal cortical network dynamics as a function of parameters that affect synaptic interactions and intrinsic states of the neurons.

| S-EPMC2585628 | biostudies-other

Large-scale topology and the default mode network in the mouse connectome.

Project description:Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)--a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans.

| S-EPMC4284535 | biostudies-literature

Single-cell gene regulation network inference by large-scale data integration.

Project description:Single-cell ATAC-seq (scATAC-seq) has proven to be a state-of-art approach to investigating gene regulation at the single-cell level. However, existing methods cannot precisely uncover cell-type-specific binding of transcription regulators (TRs) and construct gene regulation networks (GRNs) in single-cell. ChIP-seq has been widely used to profile TR binding sites in the past decades. Here, we developed SCRIP, an integrative method to infer single-cell TR activity and targets based on the integration of scATAC-seq and a large-scale TR ChIP-seq reference. Our method showed improved performance in evaluating TR binding activity compared to the existing motif-based methods and reached a higher consistency with matched TR expressions. Besides, our method enables identifying TR target genes as well as building GRNs at the single-cell resolution based on a regulatory potential model. We demonstrate SCRIP's utility in accurate cell-type clustering, lineage tracing, and inferring cell-type-specific GRNs in multiple biological systems. SCRIP is freely available at https://github.com/wanglabtongji/SCRIP.

| S-EPMC9756951 | biostudies-literature

Directed partial correlation: inferring large-scale gene regulatory network through induced topology disruptions.

Project description:Inferring regulatory relationships among many genes based on their temporal variation in transcript abundance has been a popular research topic. Due to the nature of microarray experiments, classical tools for time series analysis lose power since the number of variables far exceeds the number of the samples. In this paper, we describe some of the existing multivariate inference techniques that are applicable to hundreds of variables and show the potential challenges for small-sample, large-scale data. We propose a directed partial correlation (DPC) method as an efficient and effective solution to regulatory network inference using these data. Specifically for genomic data, the proposed method is designed to deal with large-scale datasets. It combines the efficiency of partial correlation for setting up network topology by testing conditional independence, and the concept of Granger causality to assess topology change with induced interruptions. The idea is that when a transcription factor is induced artificially within a gene network, the disruption of the network by the induction signifies a genes role in transcriptional regulation. The benchmarking results using GeneNetWeaver, the simulator for the DREAM challenges, provide strong evidence of the outstanding performance of the proposed DPC method. When applied to real biological data, the inferred starch metabolism network in Arabidopsis reveals many biologically meaningful network modules worthy of further investigation. These results collectively suggest DPC is a versatile tool for genomics research. The R package DPC is available for download (http://code.google.com/p/dpcnet/).

| S-EPMC3071805 | biostudies-literature

Large-scale directed network inference with multivariate transfer entropy and hierarchical statistical testing.

Project description:Network inference algorithms are valuable tools for the study of large-scale neuroimaging datasets. Multivariate transfer entropy is well suited for this task, being a model-free measure that captures nonlinear and lagged dependencies between time series to infer a minimal directed network model. Greedy algorithms have been proposed to efficiently deal with high-dimensional datasets while avoiding redundant inferences and capturing synergistic effects. However, multiple statistical comparisons may inflate the false positive rate and are computationally demanding, which limited the size of previous validation studies. The algorithm we present-as implemented in the IDTxl open-source software-addresses these challenges by employing hierarchical statistical tests to control the family-wise error rate and to allow for efficient parallelization. The method was validated on synthetic datasets involving random networks of increasing size (up to 100 nodes), for both linear and nonlinear dynamics. The performance increased with the length of the time series, reaching consistently high precision, recall, and specificity (>98% on average) for 10,000 time samples. Varying the statistical significance threshold showed a more favorable precision-recall trade-off for longer time series. Both the network size and the sample size are one order of magnitude larger than previously demonstrated, showing feasibility for typical EEG and magnetoencephalography experiments.

| S-EPMC6663300 | biostudies-literature

Inference for nonlinear epidemiological models using genealogies and time series.

Project description:Phylodynamics - the field aiming to quantitatively integrate the ecological and evolutionary dynamics of rapidly evolving populations like those of RNA viruses - increasingly relies upon coalescent approaches to infer past population dynamics from reconstructed genealogies. As sequence data have become more abundant, these approaches are beginning to be used on populations undergoing rapid and rather complex dynamics. In such cases, the simple demographic models that current phylodynamic methods employ can be limiting. First, these models are not ideal for yielding biological insight into the processes that drive the dynamics of the populations of interest. Second, these models differ in form from mechanistic and often stochastic population dynamic models that are currently widely used when fitting models to time series data. As such, their use does not allow for both genealogical data and time series data to be considered in tandem when conducting inference. Here, we present a flexible statistical framework for phylodynamic inference that goes beyond these current limitations. The framework we present employs a recently developed method known as particle MCMC to fit stochastic, nonlinear mechanistic models for complex population dynamics to gene genealogies and time series data in a Bayesian framework. We demonstrate our approach using a nonlinear Susceptible-Infected-Recovered (SIR) model for the transmission dynamics of an infectious disease and show through simulations that it provides accurate estimates of past disease dynamics and key epidemiological parameters from genealogies with or without accompanying time series data.

| S-EPMC3161897 | biostudies-literature

Inference-based assessment of parameter identifiability in nonlinear biological models.

Project description:As systems approaches to the development of biological models become more mature, attention is increasingly focusing on the problem of inferring parameter values within those models from experimental data. However, particularly for nonlinear models, it is not obvious, either from inspection of the model or from the experimental data, that the inverse problem of parameter fitting will have a unique solution, or even a non-unique solution that constrains the parameters to lie within a plausible physiological range. Where parameters cannot be constrained they are termed 'unidentifiable'. We focus on gaining insight into the causes of unidentifiability using inference-based methods, and compare a recently developed measure-theoretic approach to inverse sensitivity analysis to the popular Markov chain Monte Carlo and approximate Bayesian computation techniques for Bayesian inference. All three approaches map the uncertainty in quantities of interest in the output space to the probability of sets of parameters in the input space. The geometry of these sets demonstrates how unidentifiability can be caused by parameter compensation and provides an intuitive approach to inference-based experimental design.

| S-EPMC6073654 | biostudies-literature

Inference of Large-scale Time-delayed Gene Regulatory Network with Parallel MapReduce Cloud Platform.

Project description:Inference of gene regulatory network (GRN) is crucial to understand intracellular physiological activity and function of biology. The identification of large-scale GRN has been a difficult and hot topic of system biology in recent years. In order to reduce the computation load for large-scale GRN identification, a parallel algorithm based on restricted gene expression programming (RGEP), namely MPRGEP, is proposed to infer instantaneous and time-delayed regulatory relationships between transcription factors and target genes. In MPRGEP, the structure and parameters of time-delayed S-system (TDSS) model are encoded into one chromosome. An original hybrid optimization approach based on genetic algorithm (GA) and gene expression programming (GEP) is proposed to optimize TDSS model with MapReduce framework. Time-delayed GRNs (TDGRN) with hundreds of genes are utilized to test the performance of MPRGEP. The experiment results reveal that MPRGEP could infer more accurately gene regulatory network than other state-of-art methods, and obtain the convincing speedup.

| S-EPMC6290780 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data