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      NetCoMi: network construction and comparison for microbiome data in R

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          Abstract

          Motivation

          Estimating microbial association networks from high-throughput sequencing data is a common exploratory data analysis approach aiming at understanding the complex interplay of microbial communities in their natural habitat. Statistical network estimation workflows comprise several analysis steps, including methods for zero handling, data normalization and computing microbial associations. Since microbial interactions are likely to change between conditions, e.g. between healthy individuals and patients, identifying network differences between groups is often an integral secondary analysis step. Thus far, however, no unifying computational tool is available that facilitates the whole analysis workflow of constructing, analysing and comparing microbial association networks from high-throughput sequencing data.

          Results

          Here, we introduce NetCoMi ( Network Construction and comparison for Microbiome data), an R package that integrates existing methods for each analysis step in a single reproducible computational workflow. The package offers functionality for constructing and analysing single microbial association networks as well as quantifying network differences. This enables insights into whether single taxa, groups of taxa or the overall network structure change between groups. NetCoMi also contains functionality for constructing differential networks, thus allowing to assess whether single pairs of taxa are differentially associated between two groups. Furthermore, NetCoMi facilitates the construction and analysis of dissimilarity networks of microbiome samples, enabling a high-level graphical summary of the heterogeneity of an entire microbiome sample collection. We illustrate NetCoMi’s wide applicability using data sets from the GABRIELA study to compare microbial associations in settled dust from children’s rooms between samples from two study centers (Ulm and Munich).

          Availability

          R scripts used for producing the examples shown in this manuscript are provided as supplementary data. The NetCoMi package, together with a tutorial, is available at https://github.com/stefpeschel/NetCoMi.

          Contact

          Tel:+49 89 3187 43258; stefanie.peschel@mail.de

          Supplementary information

          Supplementary data are available at Briefings in Bioinformatics online.

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          Most cited references113

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          Cytoscape: a software environment for integrated models of biomolecular interaction networks.

          Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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            WGCNA: an R package for weighted correlation network analysis

            Background Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. Results The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. Conclusion The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at .
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              phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data

              Background The analysis of microbial communities through DNA sequencing brings many challenges: the integration of different types of data with methods from ecology, genetics, phylogenetics, multivariate statistics, visualization and testing. With the increased breadth of experimental designs now being pursued, project-specific statistical analyses are often needed, and these analyses are often difficult (or impossible) for peer researchers to independently reproduce. The vast majority of the requisite tools for performing these analyses reproducibly are already implemented in R and its extensions (packages), but with limited support for high throughput microbiome census data. Results Here we describe a software project, phyloseq, dedicated to the object-oriented representation and analysis of microbiome census data in R. It supports importing data from a variety of common formats, as well as many analysis techniques. These include calibration, filtering, subsetting, agglomeration, multi-table comparisons, diversity analysis, parallelized Fast UniFrac, ordination methods, and production of publication-quality graphics; all in a manner that is easy to document, share, and modify. We show how to apply functions from other R packages to phyloseq-represented data, illustrating the availability of a large number of open source analysis techniques. We discuss the use of phyloseq with tools for reproducible research, a practice common in other fields but still rare in the analysis of highly parallel microbiome census data. We have made available all of the materials necessary to completely reproduce the analysis and figures included in this article, an example of best practices for reproducible research. Conclusions The phyloseq project for R is a new open-source software package, freely available on the web from both GitHub and Bioconductor.
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                Author and article information

                Contributors
                Journal
                Brief Bioinform
                Brief Bioinform
                bib
                Briefings in Bioinformatics
                Oxford University Press
                1467-5463
                1477-4054
                July 2021
                03 December 2020
                03 December 2020
                : 22
                : 4
                : bbaa290
                Affiliations
                Institute for Asthma and Allergy Prevention , Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany
                Department of Statistics , LMU München, Munich, Germany
                Institute of Computational Biology , Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany
                Center for Computational Mathematics , Flatiron Institute, New York, USA
                Institute for Asthma and Allergy Prevention , Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany
                Dr von Hauner Children’s Hospital , LMU München, Munich, Germany
                Comprehensive Pneumology Center Munich (CPC-M) , Member of the German Center for Lung Research, Munich, Germany
                Institute for Medical Information Processing , Biometry and Epidemiology, LMU München, Munich, Germany
                Institute for Asthma and Allergy Prevention , Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany
                Author notes
                Corresponding author: Stefanie Peschel, İnstitute of Asthma and Allergy Prevention, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. Tel: +49 89 3187 43258; E-mail: stefanie.peschel@ 123456mail.de
                Article
                bbaa290
                10.1093/bib/bbaa290
                8293835
                33264391
                e9e5af1e-a8fb-4861-ab6d-237a489504fc
                © The Author(s) 2020. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 July 2020
                : 24 September 2020
                : 7 October 2020
                Page count
                Pages: 18
                Funding
                Funded by: European Commission, DOI 10.13039/501100000780;
                Award ID: LSHBCT-2006-018996
                Funded by: European Research Council, DOI 10.13039/501100000781;
                Award ID: ERC-2009-AdG_20090506_250268
                Categories
                Method Review
                AcademicSubjects/SCI01060

                Bioinformatics & Computational biology
                compositional data,microbial association estimation,sample similarity network,differential association,network analysis,network comparison

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