Neural network facilitated ab initio derivation of linear formula: A case study on formulating the relationship between DNA motifs and gene expression

Abstract: Developing models with high interpretability and even deriving formulas to quantify relationships between biological data is an emerging need. We propose here a framework for ab initio derivation of sequence motifs and linear formula using a new approach based on the interpretable neural network model called contextual regression model. We showed that this linear model could predict gene expression levels using promoter sequences with a performance comparable to deep neural network models. We uncovered a list of 300 motifs with important regulatory roles on gene expression and showed that they also had significant contributions to cell-type specific gene expression in 154 diverse cell types. This work illustrates the possibility of deriving formulas to represent biology laws that may not be easily elucidated. (https://github.com/Wang-lab-UCSD/Motif_Finding_Contextual_Regression)