Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CausalR: extracting mechanistic sense from genome scale data.

ABSTRACT:

Summary

Utilization of causal interaction data enables mechanistic rather than descriptive interpretation of genome-scale data. Here we present CausalR, the first open source causal network analysis platform. Implemented functions enable regulator prediction and network reconstruction, with network and annotation files created for visualization in Cytoscape. False positives are limited using the introduced Sequential Causal Analysis of Networks approach.

Availability and implementation

CausalR is implemented in R, parallelized, and is available from Bioconductor.

Contact

glyn.x.bradley@gsk.com.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Bradley G

PROVIDER: S-EPMC5870775 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

CausalR: extracting mechanistic sense from genome scale data.

Bradley Glyn G Barrett Steven J SJ

Bioinformatics (Oxford, England) 20171101 22

<h4>Summary</h4>Utilization of causal interaction data enables mechanistic rather than descriptive interpretation of genome-scale data. Here we present CausalR, the first open source causal network analysis platform. Implemented functions enable regulator prediction and network reconstruction, with network and annotation files created for visualization in Cytoscape. False positives are limited using the introduced Sequential Causal Analysis of Networks approach.<h4>Availability and implementatio ...[more]

PMID: 28666369

Similar Datasets

A strategy for extracting and analyzing large-scale quantitative epistatic interaction data.

Project description:Recently, approaches have been developed for high-throughput identification of synthetic sick/lethal gene pairs. However, these are only a specific example of the broader phenomenon of epistasis, wherein the presence of one mutation modulates the phenotype of another. We present analysis techniques for generating high-confidence quantitative epistasis scores from measurements made using synthetic genetic array and epistatic miniarray profile (E-MAP) technology, as well as several tools for higher-level analysis of the resulting data that are greatly enhanced by the quantitative score and detection of alleviating interactions.

| S-EPMC1779568 | biostudies-literature

Genome-scale mechanistic modeling of signaling pathways made easy: A bioconductor/cytoscape/web server framework for the analysis of omic data.

Project description:Genome-scale mechanistic models of pathways are gaining importance for genomic data interpretation because they provide a natural link between genotype measurements (transcriptomics or genomics data) and the phenotype of the cell (its functional behavior). Moreover, mechanistic models can be used to predict the potential effect of interventions, including drug inhibitions. Here, we present the implementation of a mechanistic model of cell signaling for the interpretation of transcriptomic data as an R/Bioconductor package, a Cytoscape plugin and a web tool with enhanced functionality which includes building interpretable predictors, estimation of the effect of perturbations and assessment of the effect of mutations in complex scenarios.

| S-EPMC8170118 | biostudies-literature

Mechanistic insights into bacterial metabolic reprogramming from omics-integrated genome-scale models.

Project description:Understanding the adaptive responses of individual bacterial strains is crucial for microbiome engineering approaches that introduce new functionalities into complex microbiomes, such as xenobiotic compound metabolism for soil bioremediation. Adaptation requires metabolic reprogramming of the cell, which can be captured by multi-omics, but this data remains formidably challenging to interpret and predict. Here we present a new approach that combines genome-scale metabolic modeling with transcriptomics and exometabolomics, both of which are common tools for studying dynamic population behavior. As a realistic demonstration, we developed a genome-scale model of Pseudomonas veronii 1YdBTEX2, a candidate bioaugmentation agent for accelerated metabolism of mono-aromatic compounds in soil microbiomes, while simultaneously collecting experimental data of P. veronii metabolism during growth phase transitions. Predictions of the P. veronii growth rates and specific metabolic processes from the integrated model closely matched experimental observations. We conclude that integrative and network-based analysis can help build predictive models that accurately capture bacterial adaptation responses. Further development and testing of such models may considerably improve the successful establishment of bacterial inoculants in more complex systems.

| S-EPMC6946695 | biostudies-literature

SCALPEL: EXTRACTING NEURONS FROM CALCIUM IMAGING DATA.

Project description:In the past few years, new technologies in the field of neuroscience have made it possible to simultaneously image activity in large populations of neurons at cellular resolution in behaving animals. In mid-2016, a huge repository of this so-called "calcium imaging" data was made publicly available. The availability of this large-scale data resource opens the door to a host of scientific questions for which new statistical methods must be developed. In this paper we consider the first step in the analysis of calcium imaging data-namely, identifying the neurons in a calcium imaging video. We propose a dictionary learning approach for this task. First, we perform image segmentation to develop a dictionary containing a huge number of candidate neurons. Next, we refine the dictionary using clustering. Finally, we apply the dictionary to select neurons and estimate their corresponding activity over time, using a sparse group lasso optimization problem. We assess performance on simulated calcium imaging data and apply our proposal to three calcium imaging data sets. Our proposed approach is implemented in the R package scalpel, which is available on CRAN.

| S-EPMC6269150 | biostudies-literature

Data-Driven Polymer Model for Mechanistic Exploration of Diploid Genome Organization.

Project description:Chromosomes are positioned nonrandomly inside the nucleus to coordinate with their transcriptional activity. The molecular mechanisms that dictate the global genome organization and the nuclear localization of individual chromosomes are not fully understood. We introduce a polymer model to study the organization of the diploid human genome. It is data-driven because all parameters can be derived from Hi-C data; it is also a mechanistic model because the energy function is explicitly written out based on a few biologically motivated hypotheses. These two features distinguish the model from existing approaches and make it useful both for reconstructing genome structures and for exploring the principles of genome organization. We carried out extensive validations to show that simulated genome structures reproduce a wide variety of experimental measurements, including chromosome radial positions and spatial distances between homologous pairs. Detailed mechanistic investigations support the importance of both specific interchromosomal interactions and centromere clustering for chromosome positioning. We anticipate the polymer model, when combined with Hi-C experiments, to be a powerful tool for investigating large-scale rearrangements in genome structure upon cell differentiation and tumor progression.

| S-EPMC7677132 | biostudies-literature

Cell-based screening: extracting meaning from complex data.

Project description:Unbiased discovery approaches have the potential to uncover neurobiological insights into CNS disease and lead to the development of therapies. Here, we review lessons learned from imaging-based screening approaches and recent advances in these areas, including powerful new computational tools to synthesize complex data into more useful knowledge that can reliably guide future research and development.

| S-EPMC4457442 | biostudies-literature

Extracting transcription factor targets from ChIP-Seq data.

Project description:ChIP-Seq technology, which combines chromatin immunoprecipitation (ChIP) with massively parallel sequencing, is rapidly replacing ChIP-on-chip for the genome-wide identification of transcription factor binding events. Identifying bound regions from the large number of sequence tags produced by ChIP-Seq is a challenging task. Here, we present GLITR (GLobal Identifier of Target Regions), which accurately identifies enriched regions in target data by calculating a fold-change based on random samples of control (input chromatin) data. GLITR uses a classification method to identify regions in ChIP data that have a peak height and fold-change which do not resemble regions in an input sample. We compare GLITR to several recent methods and show that GLITR has improved sensitivity for identifying bound regions closely matching the consensus sequence of a given transcription factor, and can detect bona fide transcription factor targets missed by other programs. We also use GLITR to address the issue of sequencing depth, and show that sequencing biological replicates identifies far more binding regions than re-sequencing the same sample.

| S-EPMC2761252 | biostudies-literature

Secure large-scale genome data storage and query.

Project description:BACKGROUND AND OBJECTIVE:Cloud computing plays a vital role in big data science with its scalable and cost-efficient architecture. Large-scale genome data storage and computations would benefit from using these latest cloud computing infrastructures, to save cost and speedup discoveries. However, due to the privacy and security concerns, data owners are often disinclined to put sensitive data in a public cloud environment without enforcing some protective measures. An ideal solution is to develop secure genome database that supports encrypted data deposition and query. METHODS:Nevertheless, it is a challenging task to make such a system fast and scalable enough to handle real-world demands providing data security as well. In this paper, we propose a novel, secure mechanism to support secure count queries on an open source graph database (Neo4j) and evaluated the performance on a real-world dataset of around 735,317 Single Nucleotide Polymorphisms (SNPs). In particular, we propose a new tree indexing method that offers constant time complexity (proportion to the tree depth), which was the bottleneck of existing approaches. RESULTS:The proposed method significantly improves the runtime of query execution compared to the existing techniques. It takes less than one minute to execute an arbitrary count query on a dataset of 212 GB, while the best-known algorithm takes around 7 min. CONCLUSIONS:The outlined framework and experimental results show the applicability of utilizing graph database for securely storing large-scale genome data in untrusted environment. Furthermore, the crypto-system and security assumptions underlined are much suitable for such use cases which be generalized in future work.

| S-EPMC6196742 | biostudies-literature

Extracting information from RNA SHAPE data: Kalman filtering approach.

Project description:RNA SHAPE experiments have become important and successful sources of information for RNA structure prediction. In such experiments, chemical reagents are used to probe RNA backbone flexibility at the nucleotide level, which in turn provides information on base pairing and therefore secondary structure. Little is known, however, about the statistics of such SHAPE data. In this work, we explore different representations of noise in SHAPE data and propose a statistically sound framework for extracting reliable reactivity information from multiple SHAPE replicates. Our analyses of RNA SHAPE experiments underscore that a normal noise model is not adequate to represent their data. We propose instead a log-normal representation of noise and discuss its relevance. Under this assumption, we observe that processing simulated SHAPE data by directly averaging different replicates leads to bias. Such bias can be reduced by analyzing the data following a log transformation, either by log-averaging or Kalman filtering. Application of Kalman filtering has the additional advantage that a prior on the nucleotide reactivities can be introduced. We show that the performance of Kalman filtering is then directly dependent on the quality of that prior. We conclude the paper with guidelines on signal processing of RNA SHAPE data.

| S-EPMC6248965 | biostudies-literature

Extracting multi-way chromatin contacts from Hi-C data.

Project description:There is a growing realization that multi-way chromatin contacts formed in chromosome structures are fundamental units of gene regulation. However, due to the paucity and complexity of such contacts, it is challenging to detect and identify them using experiments. Based on an assumption that chromosome structures can be mapped onto a network of Gaussian polymer, here we derive analytic expressions for n-body contact probabilities (n > 2) among chromatin loci based on pairwise genomic contact frequencies available in Hi-C, and show that multi-way contact probability maps can in principle be extracted from Hi-C. The three-body (triplet) contact probabilities, calculated from our theory, are in good correlation with those from measurements including Tri-C, MC-4C and SPRITE. Maps of multi-way chromatin contacts calculated from our analytic expressions can not only complement experimental measurements, but also can offer better understanding of the related issues, such as cell-line dependent assemblies of multiple genes and enhancers to chromatin hubs, competition between long-range and short-range multi-way contacts, and condensates of multiple CTCF anchors.

| S-EPMC8675768 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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