Journal Article

wTO: an R package for computing weighted topological overlap and a consensus network with integrated visualization tool

Voigt, Andre, Fragoso, Tiago de Miranda, Almaas, Eivind, Gysi, Deisy Morselli, Nowick, Katja

2018

Overview

Background Network analyses, such as of gene co-expression networks, metabolic networks and ecological networks have become a central approach for the systems-level study of biological data. Several software packages exist for generating and analyzing such networks, either from correlation scores or the absolute value of a transformed score called weighted topological overlap ( wTO ). However, since gene regulatory processes can up- or down-regulate genes, it is of great interest to explicitly consider both positive and negative correlations when constructing a gene co-expression network. Results Here, we present an R package for calculating the weighted topological overlap ( wTO ), that, in contrast to existing packages, explicitly addresses the sign of the wTO values, and is thus especially valuable for the analysis of gene regulatory networks. The package includes the calculation of p -values (raw and adjusted) for each pairwise gene score. Our package also allows the calculation of networks from time series (without replicates). Since networks from independent datasets (biological repeats or related studies) are not the same due to technical and biological noise in the data, we additionally, incorporated a novel method for calculating a consensus network ( CN ) from two or more networks into our R package. To graphically inspect the resulting networks, the R package contains a visualization tool, which allows for the direct network manipulation and access of node and link information. When testing the package on a standard laptop computer, we can conduct all calculations for systems of more than 20,000 genes in under two hours. We compare our new wTO package to state of art packages and demonstrate the application of the wTO and CN functions using 3 independently derived datasets from healthy human pre-frontal cortex samples. To showcase an example for the time series application we utilized a metagenomics data set. Conclusion In this work, we developed a software package that allows the computation of wTO networks, CN s and a visualization tool in the R statistical environment. It is publicly available on CRAN repositories under the GPL −2 Open Source License ( https://cran.r-project.org/web/packages/wTO/ ).

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Algorithms / Bioinformatics / Biomedical and Life Sciences / Co-expression network / Computational biology / Computational Biology - methods / Computational Biology/Bioinformatics / Computer Appl. in Life Sciences / Computer programs / Consensus / Consensus Network / Correlation analysis / Cortex (frontal) / Data processing / Datasets / Ecological monitoring / Escherichia coli - metabolism / Expression / Gene expression / Gene Ontology / Gene Regulatory Networks / Genes / Genetic engineering / Humans / Life Sciences / Mathematical analysis / Meta-analysis / Metabolic networks / Metabolic Networks and Pathways / Metabolism / Metagenomics / Microarrays / Network / Networks / Networks analysis / Oceans and Seas / R package / Repositories / ROC Curve / Software / Software packages / Statistical analysis / Statistical methods / Time Factors / Time series / Transcription factors / Transcription Factors - metabolism / Visualization / Visualization (Computer)