Abstract
Recent studies have shown that the microbiome can impact cancer development, progression, and response to therapies suggesting microbiome-based approaches for cancer characterization. As cancer-related signatures are complex and implicate many taxa, their discovery often requires Machine Learning approaches. This review discusses Machine Learning methods for cancer characterization from microbiome data. It focuses on the implications of choices undertaken during sample collection, feature selection and pre-processing. It also discusses ML model selection, guiding how to choose an ML model, and model validation. Finally, it enumerates current limitations and how these may be surpassed. Proposed methods, often based on Random Forests, show promising results, however insufficient for widespread clinical usage. Studies often report conflicting results mainly due to ML models with poor generalizability. We expect that evaluating models with expanded, hold-out datasets, removing technical artifacts, exploring representations of the microbiome other than taxonomical profiles, leveraging advances in deep learning, and developing ML models better adapted to the characteristics of microbiome data will improve the performance and generalizability of models and enable their usage in the clinic.