Application of Machine Learning Methods in Predicting Nuclear Receptors and their Families

Nuclear receptors (NRs) are a superfamily of ligand-dependent transcription factors that are closely related to cell development, differentiation, reproduction, homeostasis, and metabolism. According to the alignments of the conserved domains, NRs are classified and assigned the following seven subfamilies or eight subfamilies: (1) NR1: thyroid hormone like (thyroid hormone, retinoic acid, RAR-related orphan receptor, peroxisome proliferator activated, vitamin D3- like), (2) NR2: HNF4-like (hepatocyte nuclear factor 4, retinoic acid X, tailless-like, COUP-TFlike, USP), (3) NR3: estrogen-like (estrogen, estrogen-related, glucocorticoid-like), (4) NR4: nerve growth factor IB-like (NGFI-B-like), (5) NR5: fushi tarazu-F1 like (fushi tarazu-F1 like), (6) NR6: germ cell nuclear factor like (germ cell nuclear factor), and (7) NR0: knirps like (knirps, knirpsrelated, embryonic gonad protein, ODR7, trithorax) and DAX like (DAX, SHP), or dividing NR0 into (7) NR7: knirps like and (8) NR8: DAX like. Different NRs families have different structural features and functions. Since the function of a NR is closely correlated with which subfamily it belongs to, it is highly desirable to identify NRs and their subfamilies rapidly and effectively. The knowledge acquired is essential for a proper understanding of normal and abnormal cellular mechanisms. With the advent of the post-genomics era, huge amounts of sequence-known proteins have increased explosively. Conventional methods for accurately classifying the family of NRs are experimental means with high cost and low efficiency. Therefore, it has created a greater need for bioinformatics tools to effectively recognize NRs and their subfamilies for the purpose of understanding their biological function. In this review, we summarized the application of machine learning methods in the prediction of NRs from different aspects. We hope that this review will provide a reference for further research on the classification of NRs and their families.