Gene regulatory network inference based on novel ensemble method

Gene regulatory networks (GRNs) contribute toward understanding the function of genes and the development of cancer or the impact of key genes on diseases. Hence, this study proposes an ensemble method based on 13 basic classification methods and a flexible neural tree (FNT) to improve GRN identification accuracy. The primary classification methods contain ridge classification, stochastic gradient descent, Gaussian process classification, Bernoulli Naive Bayes, adaptive boosting, gradient boosting decision tree, hist gradient boosting classification, eXtreme gradient boosting (XGBoost), multilayer perceptron, light gradient boosting machine, random forest, support vector machine, and k-nearest neighbor algorithm, which are regarded as the input variable set of FNT model. Additionally, a hybrid evolutionary algorithm based on a gene programming variant and particle swarm optimization is developed to search for the optimal FNT model. Experiments on three simulation datasets and three real single-cell RNA-seq datasets demonstrate that the proposed ensemble feature outperforms 13 supervised algorithms, seven unsupervised algorithms (ARACNE, CLR, GENIE3, MRNET, PCACMI, GENECI, and EPCACMI) and four single cell-specific methods (SCODE, BiRGRN, LEAP, and BiGBoost) based on the area under the receiver operating characteristic curve, area under the precision-recall curve, and F1 metrics.