Inverse Potts model improves accuracy of phylogenetic profiling

Motivation: Phylogenetic profiling is a powerful computational method for revealing the functions of function-unknown genes. Although conventional similarity metrics in phylogenetic profiling achieved high prediction accuracy, they have two estimation biases: an evolutionary bias and a spurious correlation bias. While previous studies reduced the evolutionary bias by considering a phylogenetic tree, few studies have analyzed the spurious correlation bias. Results: To reduce the spurious correlation bias, we developed metrics based on the inverse Potts model (IPM) for phylogenetic profiling. We also developed a metric based on both the IPM and a phylogenetic tree. In an empirical dataset analysis, we demonstrated that these IPM-based metrics improved the prediction performance of phylogenetic profiling. In addition, we found that the integration of several metrics, including the IPM-based metrics, had superior performance to a single metric.