Benchmark of data processing methods and machine learning models for gut microbiome-based diagnosis of inflammatory bowel disease

Background Inflammatory bowel disease (IBD) patients wait months and undergo numerous invasive procedures between the initial appearance of symptoms and receiving a diagnosis. In order to reduce time until diagnosis and improve patient wellbeing, machine learning algorithms capable of diagnosing IBD from the gut microbiome’s composition are currently being explored. To date, these models have had limited clinical application due to decreased performance when applied to a new cohort of patient samples. Various methods have been developed to analyze microbiome data which may improve the generalizability of machine learning IBD diagnostic tests. With an abundance of methods, there is a need to benchmark the performance and generalizability of various machine learning pipelines (from data processing to training a machine learning model) for microbiome-based IBD diagnostic tools. Results We collected fifteen 16S rRNA microbiome datasets (7707 samples) from North America to benchmark combinations of gut microbiome features, data normalization methods, batch effect reduction methods, and machine learning models. Pipeline generalizability to new cohorts of patients was evaluated with four binary classification metrics following leave-one dataset-out cross validation, where all samples from one study were left out of the training set and tested upon. We demonstrate that taxonomic features obtained from QIIME2 lead to better classification of samples from IBD patients than inferred functional features obtained from PICRUSt2. In addition, machine learning models that identify non-linear decision boundaries between labels are more generalizable than those that are linearly constrained. Prior to training a non-linear machine learning model on taxonomic features, it is important to apply a compositional normalization method and remove batch effects with the naive zero-centering method. Lastly, we illustrate the importance of generating a curated training dataset to ensure similar performance across patient demographics. Conclusions These findings will help improve the generalizability of machine learning models as we move towards non-invasive diagnostic and disease management tools for patients with IBD.