Harmonies: A hybrid approach for microbiome networks inference via exploiting sparsity

Shuang Jiang, Guanghua Xiao, Andrew Y. Koh, Yingfei Chen, Bo Yao, Qiwei Li, Xiaowei Zhan

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The human microbiome is a collection of microorganisms. They form complex communities and collectively affect host health. Recently, the advances in next-generation sequencing technology enable the high-throughput profiling of the human microbiome. This calls for a statistical model to construct microbial networks from the microbiome sequencing count data. As microbiome count data are high-dimensional and suffer from uneven sampling depth, over-dispersion, and zero-inflation, these characteristics can bias the network estimation and require specialized analytical tools. Here we propose a general framework, HARMONIES, Hybrid Approach foR MicrobiOme Network Inferences via Exploiting Sparsity, to infer a sparse microbiome network. HARMONIES first utilizes a zero-inflated negative binomial (ZINB) distribution to model the skewness and excess zeros in the microbiome data, as well as incorporates a stochastic process prior for sample-wise normalization. This approach infers a sparse and stable network by imposing non-trivial regularizations based on the Gaussian graphical model. In comprehensive simulation studies, HARMONIES outperformed four other commonly used methods. When using published microbiome data from a colorectal cancer study, it discovered a novel community with disease-enriched bacteria. In summary, HARMONIES is a novel and useful statistical framework for microbiome network inference, and it is available at https://github.com/shuangj00/HARMONIES.

Original languageEnglish (US)
Article number445
JournalFrontiers in Genetics
StatePublished - 2020


  • Bayesian statistics
  • Dirichlet process prior
  • Gaussian graphical model
  • Hierarchical model
  • Microbiome network

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)


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