Abstract

Microorganisms including bacteria, fungi, viruses, protists and archaea live as communities in complex and contiguous environments. They engage in numerous inter- and intra- kingdom interactions which can be inferred from microbiome profiling data. In particular, network-based approaches have proven helpful in deciphering complex microbial interaction patterns. Here we give an overview of state-of-the-art methods to infer intra-kingdom interactions ranging from simple correlation- to complex conditional dependence-based methods. We highlight common biases encountered in microbial profiles and discuss mitigation strategies employed by different tools and their trade-off with increased computational complexity. Finally, we discuss current limitations that motivate further method development to infer inter-kingdom interactions and to robustly and comprehensively characterize microbial environments in the future.

Highlights

  • The human body acts as a host for complex microbial communities consisting of bacteria, protozoa, archaea, viruses and fungi [1]

  • Microorganisms have built complex and robust ecosystems in various environments ranging from soil or sea water to various organs of the human body

  • Understanding the nature of microbial co-occurrence and correlation patterns within and between kingdoms may provide insights into the robustness of ecological systems and offer insights into complex human diseases such as inflammatory bowel disease, which is known to be influenced by the microbiome

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Summary

Introduction

The human body acts as a host for complex microbial communities consisting of bacteria, protozoa, archaea, viruses and fungi [1]. Next-generation sequencing techniques proved very effective for characterizing microbial communities by sequencing suitable molecular targets such as 16S ribosomal RNA gene amplicons for bacteria, internal transcribed spacer regions of ribosomal RNA genes for fungi and shotgun metagenomics for viruses (Fig. 1A). Since these organisms share the same host, they are in constant competition, where some organisms develop symbiotic relationships in which they cooperate or synergize with each other for gaining a fitness advantage that may or may not benefit the host organism [2,3].

Network methods for microbial communities
Correlation based methods
Limitation
Regularized linear regression
Association rule mining
Conditional dependence and graphical methods
Addressing network topology bias
Methods scaling to large-scale data
Multi-view networks
10. Differential network analysis
11. Inferring interaction types
12. Studying microbiome time-series dynamics
13. Network-based methods for trans-kingdom analysis
Findings
14. Discussion
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