“…Furthermore, Machine learning-based methods are capable of discovering non-linear hidden motifs of enhancers. To date, there are at least twenty machine learning-based methods for enhancer prediction [ 16 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ], such as iEnhancer-2L [ 40 ], iEnhancer-PsedeKNC [ 41 ], EnhancerPred [ 42 ], and EnhancerPred2.0 [ 43 ]. The general workflow of these methods is firstly to compute representation of sequences such as pseudo k-tuple nucleotide composition, nucleotide binary profiles, as well as accumulated nucleotide frequency, then to learn a classifier by using a machine learning algorithm such as support vector machine and random forest, and finally to predict unknown sequences.…”