Abstract
MOTIVATION: With advances in metagenomic sequencing technologies, there are accumulating studies revealing the associations between the human gut microbiome and some human diseases. These associations shed light on using gut microbiome data to distinguish case and control samples of a specific disease, which is also called host disease status classification. Importantly, using learning-based models to distinguish the disease and control samples is expected to identify important biomarkers more accurately than abundance-based statistical analysis. However, available tools have not fully addressed two challenges associated with this task: limited labeled microbiome data and decreased accuracy in cross-studies. The confounding factors, such as the diet, technical biases in sample collection/sequencing across different studies/cohorts often jeopardize the generalization of the learning model. RESULTS: To address these challenges, we develop a new tool GDmicro, which combines semi-supervised learning and domain adaptation to achieve a more generalized model using limited labeled samples. We evaluated GDmicro on human gut microbiome data from 11 cohorts covering 5 different diseases. The results show that GDmicro has better performance and robustness than state-of-the-art tools. In particular, it improves the AUC from 0.783 to 0.949 in identifying inflammatory bowel disease. Furthermore, GDmicro can identify potential biomarkers with greater accuracy than abundance-based statistical analysis methods. It also reveals the contribution of these biomarkers to the host's disease status. AVAILABILITY AND IMPLEMENTATION: https://github.com/liaoherui/GDmicro.