Enhanced metagenomic deep learning for disease prediction and consistent signature recognition by restructured microbiome 2D representations

Metagenomic analysis has been explored for disease diagnosis and biomarker discovery. Low sample sizes, high dimensionality, and sparsity of metagenomic data challenge metagenomic investigations. Here, an unsupervised microbial embedding, grouping, and mapping algorithm (MEGMA) was developed to transform metagenomic data into individualized multichannel microbiome 2D representation by manifold learning and clustering of microbial profiles (e.g., composition, abundance, hierarchy, and taxonomy). These 2D representations enable enhanced disease prediction by established ConvNet-based AggMapNet models, outperforming the commonly used machine learning and deep learning models in metagenomic benchmark datasets. These 2D representations combined with AggMapNet explainable module robustly identified more reliable and replicable disease-prediction microbes (biomarkers). Employing the MEGMA-AggMapNet pipeline for biomarker identification from 5 disease datasets, 84% of the identified biomarkers have been described in over 74 distinct works as important for these diseases. Moreover, the method also discovered highly consistent sets of biomarkers in cross-cohort colorectal cancer (CRC) patients and microbial shifts in different CRC stages.