Interpretable Deep Learning for Studying Transcriptional and Post-Transcriptional Regulations




Zhang, Tinghe

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Transcription regulation and post-transcription regulation are critical biological processes for organisms' development, complexity, and homeostasis. Understanding the mechanisms of these processes will be helpful for biologists to reveal the secret of life. Traditionally, biological discoveries are achieved mainly by experiments. However, the experiments are costly and time-consuming. Developing computation tools that elucidate biological functions from data can accelerate biological discovery. In this study, we focused on three topics to investigate functional predictions of three different phases of Transcription and post-transcription regulation by interpretable deep learning methods. We first considered the prediction of enhancers, which are cis-acting DNA regulatory regions that play a key role in increasing the transcription of specific genes via interaction with transcription factors. We designed a CNN-based residual neural network to identify enhancers and their strength. A 4% accuracy improvement in independent tests shows that the proposed model can effectively predict the enhancer's strength. Then, we investigated the prediction of YTHDF2-mediated mRNA degradation based on mRNA sequences and proposed m6ABERT, a transformer-based model. Our models reported at least 2.5% improvement in accuracy than other models. Besides, we discovered the potential RNA binding proteins that affect the degradation by interpreting m6ABERT.For gene expression, we proposed an interpretable gene expression-based deep learning model, T-GEM, for phenotype prediction and gene regulatory network discovery. We showed the competitive performance with existing models and the advantage of the model's interpretability. We also revealed the learning mechanism of T-GEM and devised a method to extract the regulatory network from T-GEM.


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Deep learning, Transcription regulation, mRNA degradation, Gene expression



Electrical and Computer Engineering