C3NA: correlation and consensus-based cross-taxonomy network analysis for compositional microbial data

Abstract

Background: Studying the co-occurrence network structure of microbial samples is one of the critical approaches to understanding the perplexing and delicate relationship between the microbe, host, and diseases. It is also critical to develop a tool for investigating co-occurrence networks and differential abundance analyses to reveal the disease-related taxa–taxa relationship. In addition, it is also necessary to tighten the co-occurrence network into smaller modules to increase the ability for functional annotation and interpretability of these taxa-taxa relationships. Also, it is critical to retain the phylogenetic relationship among the taxa to identify differential abundance patterns, which can be used to resolve contradicting functions reported by different studies. Results: In this article, we present Correlation and Consensus-based Cross-taxonomy Network Analysis (C3NA), a user-friendly R package for investigating compositional microbial sequencing data to identify and compare co-occurrence patterns across different taxonomic levels. C3NA contains two interactive graphic user interfaces (Shiny applications), one of them dedicated to the comparison between two diagnoses, e.g., disease versus control. We used C3NA to analyze two well-studied diseases, colorectal cancer, and Crohn’s disease. We discovered clusters of study and disease-dependent taxa that overlap with known functional taxa studied by other discovery studies and differential abundance analyses. Conclusion: C3NA offers a new microbial data analyses pipeline for refined and enriched taxa–taxa co-occurrence network analyses, and the usability was further expanded via the built-in Shiny applications for interactive investigation.