Forward variable selection improves the power of random forest for high- dimensional microbiome data

Background Random forest (RF) captures complex feature patterns that differentiate groups of samples and is rapidly being adopted in microbiome studies. However, a major challenge is the high dimensionality of microbiome datasets. They include thousands of species or molecular functions of particular biological interest. This high dimensionality significantly reduces the power of random forest approaches for identifying true differences. The widely used Boruta algorithm iteratively removes features that are proved by a statistical test to be less relevant than random probes. Result We developed a massively parallel forward variable selection algorithm and coupled it with the RF classifier to maximize the predictive performance. The forward variable selection algorithm adds new variable to a set of selected variables as far as the prespecified criterion of predictive power is improved. At each step, the parameters of random forest are optimized. We demonstrated the performance of the proposed approach, which we named RF-FVS, by analyzing two published datasets from large-scale case-control studies: (i) 16S rRNA gene amplicon data for Clostridioides difficile infection (CDI) and (ii) shotgun metagenomics data for human colorectal cancer (CRC). The RF-FVS approach further screened the variables that the Boruta algorithm left and improved the accuracy of the random forest classifier from 81% to 99.01% for CDI and from 75.14% to 90.17% for CRC. Conclusion Valid variable selection is essential for the analysis of high-dimensional microbiota data. By adopting the Boruta algorithm for pre-screening of the variables, our proposed RF-FVS approach improves the accuracy of random forest significantly with minimum increase of computational burden. The procedure can be used to identify the functional profiles that differentiate samples between different conditions.