scholarly journals SILGGM: An extensive R package for efficient statistical inference in large-scale gene networks

2018 ◽  
Vol 14 (8) ◽  
pp. e1006369 ◽  
Author(s):  
Rong Zhang ◽  
Zhao Ren ◽  
Wei Chen
Keyword(s):  
Statistical Inference ◽  
Gene Networks ◽  
Large Scale ◽  
R Package

scholarly journals graphsim: An R package for simulating gene expression data from graph structures of biological pathways

2020 ◽  
Author(s):  
S. Thomas Kelly ◽  
Michael A. Black
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Large Scale ◽  
Simulated Data ◽  
R Package ◽  
Biological Pathways ◽  
Graph Structure ◽  
Expression Data

SummaryTranscriptomic analysis is used to capture the molecular state of a cell or sample in many biological and medical applications. In addition to identifying alterations in activity at the level of individual genes, understanding changes in the gene networks that regulate fundamental biological mechanisms is also an important objective of molecular analysis. As a result, databases that describe biological pathways are increasingly uesad to assist with the interpretation of results from large-scale genomics studies. Incorporating information from biological pathways and gene regulatory networks into a genomic data analysis is a popular strategy, and there are many methods that provide this functionality for gene expression data. When developing or comparing such methods, it is important to gain an accurate assessment of their performance. Simulation-based validation studies are frequently used for this. This necessitates the use of simulated data that correctly accounts for pathway relationships and correlations. Here we present a versatile statistical framework to simulate correlated gene expression data from biological pathways, by sampling from a multivariate normal distribution derived from a graph structure. This procedure has been released as the graphsim R package on CRAN and GitHub (https://github.com/TomKellyGenetics/graphsim) and is compatible with any graph structure that can be described using the igraph package. This package allows the simulation of biological pathways from a graph structure based on a statistical model of gene expression.

scholarly journals Directed Conservative Causal Core Gene Networks

2018 ◽  
Author(s):  
Gokmen Altay
Keyword(s):  
Gene Networks ◽  
Large Scale ◽  
Network Inference ◽  
R Package ◽  
Core Gene ◽  
Supplementary Information ◽  
Supplementary File ◽  
Core Network ◽  
Large Scale Networks ◽  
Direction Information

AbstractMotivation:Inferring large scale directional networks with higher accuracy has important applications such as gene regulatory network or finance.Results:We modified a well-established conservative causal core network inference algorithm, C3NET, to be able to infer very large scale networks with direction information. This advanced version is called Ac3net. We demonstrate that Ac3net outperforms C3NET and many other popular algorithms when considering the directional interaction information of gene/protein networks. We provide and R package and present performance results that are reproducible via the Supplementary file.Availability:Ac3net is available on CRAN and at github.com/altayg/Ac3netContact:[email protected] information:Supplementary file is available online.

scholarly journals Analysis of blood-based gene expression in idiopathic Parkinson disease

Neurology ◽  
2017 ◽  
Vol 89 (16) ◽  
pp. 1676-1683 ◽  
Author(s):  
Ron Shamir ◽  
Christine Klein ◽  
David Amar ◽  
Eva-Juliane Vollstedt ◽  
Michael Bonin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson Disease ◽  
Gene Networks ◽  
Large Scale ◽  
Expression Profiles ◽  
Area Under The Curve ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Gene Profiles ◽  
Independent Test

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).Methods:Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.Results:A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E–6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E–4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1, ATP5A1, and VDAC3.Conclusions:We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers.

Sex differences in white adipose tissue expansion: emerging molecular mechanisms

2021 ◽  
Vol 135 (24) ◽  
pp. 2691-2708
Author(s):  
Simon T. Bond ◽  
Anna C. Calkin ◽  
Brian G. Drew
Keyword(s):  
Sex Differences ◽  
Sexual Dimorphism ◽  
Gene Networks ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Tissue Expansion ◽  
Economic Systems ◽  
Genomic Association ◽  
Males And Females

Abstract The escalating prevalence of individuals becoming overweight and obese is a rapidly rising global health problem, placing an enormous burden on health and economic systems worldwide. Whilst obesity has well described lifestyle drivers, there is also a significant and poorly understood component that is regulated by genetics. Furthermore, there is clear evidence for sexual dimorphism in obesity, where overall risk, degree, subtype and potential complications arising from obesity all differ between males and females. The molecular mechanisms that dictate these sex differences remain mostly uncharacterised. Many studies have demonstrated that this dimorphism is unable to be solely explained by changes in hormones and their nuclear receptors alone, and instead manifests from coordinated and highly regulated gene networks, both during development and throughout life. As we acquire more knowledge in this area from approaches such as large-scale genomic association studies, the more we appreciate the true complexity and heterogeneity of obesity. Nevertheless, over the past two decades, researchers have made enormous progress in this field, and some consistent and robust mechanisms continue to be established. In this review, we will discuss some of the proposed mechanisms underlying sexual dimorphism in obesity, and discuss some of the key regulators that influence this phenomenon.

scholarly journals Feasibility and Evaluation of a Large-Scale External Validation Approach for Patient-Level Prediction in an International Data Network: Validation of models predicting stroke in female patients newly diagnosed with atrial fibrillation.

2020 ◽  
Author(s):  
Jenna Marie Reps ◽  
Ross Williams ◽  
Seng Chan You ◽  
Thomas Falconer ◽  
Evan Minty ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Large Scale ◽  
Data Science ◽  
Prediction Models ◽  
External Validation ◽  
Scale Up ◽  
R Package ◽  
Prognostic Models ◽  
Healthcare Data ◽  
Patient Level

Abstract Objective: To demonstrate how the Observational Healthcare Data Science and Informatics (OHDSI) collaborative network and standardization can be utilized to scale-up external validation of patient-level prediction models by enabling validation across a large number of heterogeneous observational healthcare datasets.Materials & Methods: Five previously published prognostic models (ATRIA, CHADS2, CHADS2VASC, Q-Stroke and Framingham) that predict future risk of stroke in patients with atrial fibrillation were replicated using the OHDSI frameworks. A network study was run that enabled the five models to be externally validated across nine observational healthcare datasets spanning three countries and five independent sites. Results: The five existing models were able to be integrated into the OHDSI framework for patient-level prediction and they obtained mean c-statistics ranging between 0.57-0.63 across the 6 databases with sufficient data to predict stroke within 1 year of initial atrial fibrillation diagnosis for females with atrial fibrillation. This was comparable with existing validation studies. The validation network study was run across nine datasets within 60 days once the models were replicated. An R package for the study was published at https://github.com/OHDSI/StudyProtocolSandbox/tree/master/ExistingStrokeRiskExternalValidation.Discussion: This study demonstrates the ability to scale up external validation of patient-level prediction models using a collaboration of researchers and a data standardization that enable models to be readily shared across data sites. External validation is necessary to understand the transportability or reproducibility of a prediction model, but without collaborative approaches it can take three or more years for a model to be validated by one independent researcher. Conclusion : In this paper we show it is possible to both scale-up and speed-up external validation by showing how validation can be done across multiple databases in less than 2 months. We recommend that researchers developing new prediction models use the OHDSI network to externally validate their models.

scholarly journals Optimizing smartphone-based canopy hemispherical photography

2021 ◽  
Author(s):  
Gastón Mauro Díaz
Keyword(s):  
Large Scale ◽  
Forest Canopy ◽  
Accuracy Assessment ◽  
Low Cost ◽  
R Package ◽  
Coefficient Of Determination ◽  
Native Forest ◽  
Hemispherical Photography ◽  
Area Index ◽  
Plant Area Index

1) Hemispherical photography (HP) is a long-standing tool for forest canopy characterization. Currently, there are low-cost fisheye lenses to convert smartphones into high-portable HP equipment; however, they cannot be used whenever since HP is sensitive to illumination conditions. To obtain sound results outside diffuse light conditions, a deep-learning-based system needs to be developed. A ready-to-use alternative is the multiscale color-based binarization algorithm, but it can provide moderate-quality results only for open forests. To overcome this limitation, I propose coupling it with the model-based local thresholding algorithm. I call this coupling the MBCB approach. 2) Methods presented here are part of the R package CAnopy IMage ANalysis (caiman), which I am developing. The accuracy assessment of the new MBCB approach was done with data from a pine plantation and a broadleaf native forest. 3) The coefficient of determination (R^2) was greater than 0.7, and the root mean square error (RMSE) lower than 20 %, both for plant area index calculation. 4) Results suggest that the new MBCB approach allows the calculation of unbiased canopy metrics from smartphone-based HP acquired in sunlight conditions, even for closed canopies. This facilitates large-scale and opportunistic sampling with hemispherical photography.

scholarly journals Implementation of the Omega (ω) Index to detect large-scale systematic cheating

2019 ◽  
Author(s):  
Alvin Vista
Keyword(s):  
Standardized Testing ◽  
Large Scale ◽  
Type I Error ◽  
R Package ◽  
Statistical Testing ◽  
System Level ◽  
Control Group ◽  
Type I ◽  
Data Contamination ◽  
Cheating Detection

Cheating detection is an important issue in standardized testing, especially in large-scale settings. Statistical approaches are often computationally intensive and require specialised software to conduct. We present a two-stage approach that quickly filters suspected groups using statistical testing on an IRT-based answer-copying index. We also present an approach to mitigate data contamination and improve the performance of the index. The computation of the index was implemented through a modified version of an open source R package, thus enabling wider access to the method. Using data from PIRLS 2011 (N=64,232) we conduct a simulation to demonstrate our approach. Type I error was well-controlled and no control group was falsely flagged for cheating, while 16 (combined n=12,569) of the 18 (combined n=14,149) simulated groups were detected. Implications for system-level cheating detection and further improvements of the approach were discussed.

scholarly journals FrustratometeR: an R-package to compute Local frustration in protein structures, point mutants and MD simulations

2020 ◽  
Author(s):  
Atilio O. Rausch ◽  
Maria I. Freiberger ◽  
Cesar O. Leonetti ◽  
Diego M. Luna ◽  
Leandro G. Radusky ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Protein Structures ◽  
Md Simulations ◽  
R Package ◽  
Protein Protein Interactions ◽  
Large Scale Analysis ◽  
Functional Aspects ◽  
Catalytic Sites ◽  
Polypeptide Chains

Once folded natural protein molecules have few energetic conflicts within their polypeptide chains. Many protein structures do however contain regions where energetic conflicts remain after folding, i.e. they have highly frustrated regions. These regions, kept in place over evolutionary and physiological timescales, are related to several functional aspects of natural proteins such as protein-protein interactions, small ligand recognition, catalytic sites and allostery. Here we present FrustratometeR, an R package that easily computes local energetic frustration on a personal computer or a cluster. This package facilitates large scale analysis of local frustration, point mutants and MD trajectories, allowing straightforward integration of local frustration analysis in to pipelines for protein structural analysis.Availability and implementation: https://github.com/proteinphysiologylab/frustratometeR

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