An Integrated Machine-Learning Model to Predict Prokaryotic Essential Genes

Abstract

Essential genes are indispensable for the target organism’s survival. Large-scale identification and characterization of essential genes has shown to be beneficial in both fundamental biology and medicine fields. Current existing genome-scale experimental screenings of essential genes are time consuming and costly, also sometimes confer erroneous essential gene annotations. To circumvent these difficulties, many research groups turn to computational approaches as the alternative to identify essential genes. Here, we developed an integrative machine-learning based statistical framework to accurately predict essential genes in microorganisms. First we extracted a variety of relevant features derived from different aspects of an organism’s genomic sequences. Then we selected a subset of features have high predictive power of gene essentiality through a carefully designed feature selection system. Using the selected features as input, we constructed an ensemble classifier and trained the model on a well-studied microorganism. After fine-tuning the model parameters in cross-validation, we tested the model on the other microorganism. We found that the tenfold cross-validation results within the same organism achieves a high predictive accuracy (AUC ~0.9), and cross-organism predictions between distant related organisms yield the AUC scores from 0.69 to 0.89, which significantly outperformed homology mapping.