Evaluation of metabolite-microbe correlation detection methods.

Different correlation detection methods have been specifically designed for the microbiome data analysis considering the compositional data structure and different sequencing depths. Along with the speedy development of omics studies, there is an increasing interest in discovering the biological associations between microbes and host metabolites. This raises the need of finding proper statistical methods that facilitate the correlation analysis across different omics studies. Here, we comprehensively evaluated six different correlation methods, i.e., Pearson correlation, Spearman correlation, Sparse Correlations for Compositional data (SparCC), Correlation inference for Compositional data through Lasso (CCLasso), Mutual Information Coefficient (MIC), and Cosine similarity methods, for the correlations detection between microbes and metabolites. Three simulated and two real-world data sets (from public databases and our lab) were used to examine the performance of each method regarding its specificity, sensitivity, similarity, accuracy, and stability with different sparsity. Our results indicate that although each method has its own pros and cons in different scenarios, Spearman correlation and MIC outperform the others with their overall performances. A strategic guidance was also proposed for the correlation analysis between microbe and metabolite.