CorrelationCalculator and Filigree: Tools for Data-Driven Network Analysis of Metabolomics Data

Summary

We present CorrelationCalculator and Filigree, two tools for data-driven network construction and analysis of metabolomics data. CorrelationCalculator supports building a single interaction network of metabolites based on expression data, while Filigree allows building a differential network, followed by network clustering and enrichment analysis.

Abstract

A significant challenge in the analysis of omics data is extracting actionable biological knowledge. Metabolomics is no exception. The general problem of relating changes in levels of individual metabolites to specific biological processes is compounded by the large number of unknown metabolites present in untargeted liquid chromatography-mass spectrometry (LC-MS) studies. Further, secondary metabolism and lipid metabolism are poorly represented in existing pathway databases. To overcome these limitations, our group has developed several tools for data-driven network construction and analysis. These include CorrelationCalculator and Filigree. Both tools allow users to build partial correlation-based networks from experimental metabolomics data when the number of metabolites exceeds the number of samples. CorrelationCalculator supports the construction of a single network, while Filigree allows building a differential network utilizing data from two groups of samples, followed by network clustering and enrichment analysis. We will describe the utility and application of both tools for the analysis of real-life metabolomics data.

Introduction

In the last decade, metabolomics has emerged as an omics science due to advances in analytical technologies such as Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS). These techniques allow simultaneous measurement of hundreds to thousands of small molecule metabolites, creating complex multidimensional datasets. Metabolomics experiments can be performed in targeted or untargeted modes. Targeted metabolomics experiments measure specific classes of metabolites. They are usually hypothesis-driven, while untargeted approaches attempt to measure as many metabolites as possible and are hypothesis-generating in nature. Targeted....

Protocol

1. CorrelationCalculator

1. Download a sample comma-delimited input file containing a list of metabolites with experimental measurements at http://metscape.med.umich.edu/kora_data_240.csv.
2. Double-click on the downloaded sample file to open it.
   1. Ensure that the file contains labels for both the samples and the metabolites.
   2. Since samples are in rows, confirm that the first column is the sample names and the first row is the metabolite names.
3. Download the CorrelationCalculator Java application (http://metscape.med.umich.edu/calculator.html). Double-click on the downloaded .jar file to ....

Results

To illustrate the use of CorrelationCalculator, we constructed a partial correlation network using a subset of the metabolomics data from the KORA population study described in Krumsiek et al.²⁴. The dataset contained 151 metabolites and 240 samples. Figure 1 shows the resulting partial correlation network that was visualized in Cytoscape. The network contains 148 nodes and 272 edges. The color of the nodes represents metabolites that belong to different chem.......

Discussion

Partial correlation-based network analysis methods implemented in CorrelationCalculator and Filigree help overcome some of the limitations of knowledge-based metabolic pathway analyses, especially for the datasets with a high prevalence of unknown metabolites and limited coverage of metabolic pathways (e.g., lipidomics data). These tools have been widely used by the research community to analyze a broad range of metabolomics and lipidomics data^14,22,

Materials

Name	Company	Catalog Number	Comments
CorrelationCalculator	JAVA	http://metscape.med.umich.edu/calculator.html
clusterNet		https://github.com/Karnovsky-Lab/clusterNet
Cytoscape	Cytoscape	https://cytoscape.org/
Filigree	JAVA	http://metscape.med.umich.edu/filigree.html
MetScape	Cytoscape	https://apps.cytoscape.org/apps/metscape	Cytoscape application that allows for the creation and exploration of correlation networks.