# Bridging the gap between target-based and cell-based drug discovery with a graph generative multi-task model

arXiv: https://arxiv.org/abs/2208.04944 · HTML: https://mlsanity.com/paper/2208.04944/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 8 of its 35 references that are in the map.
- First posted on arXiv 9 Aug 2022.

## Builds on (most cited first, 8 of 8)

- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Learning Phrase Representations using RNN Encoder-Decoder for Statistical Machine Translation](https://mlsanity.com/paper/1406.1078/) (2014)
- [Fast and Accurate Deep Network Learning by Exponential Linear Units (ELUs)](https://mlsanity.com/paper/1511.07289/) (2015)
- [An Overview of Multi-Task Learning in Deep Neural Networks](https://mlsanity.com/paper/1706.05098/) (2017)
- [Cross-stitch Networks for Multi-task Learning](https://mlsanity.com/paper/1604.03539/) (2016)
- [DeepDTA: Deep Drug-Target Binding Affinity Prediction](https://mlsanity.com/paper/1801.10193/) (2018)
- [Development and evaluation of a deep learning model for protein-ligand binding affinity prediction](https://mlsanity.com/paper/1712.07042/) (2017)
- [A Novel Framework Integrating AI Model and Enzymological Experiments Promotes Identification of SARS-CoV-2 3CL Protease Inhibitors and Activity-based Probe](https://mlsanity.com/paper/2105.14224/) (2021)

## Abstract (arXiv)

Drug discovery is vitally important for protecting human against disease. Target-based screening is one of the most popular methods to develop new drugs in the past several decades. This method efficiently screens candidate drugs inhibiting target protein in vitro, but it often fails due to inadequate activity of the selected drugs in vivo. Accurate computational methods are needed to bridge this gap. Here, we propose a novel graph multi task deep learning model to identify compounds carrying both target inhibitory and cell active (MATIC) properties. On a carefully curated SARS-CoV-2 dataset, the proposed MATIC model shows advantages comparing with traditional method in screening effective compounds in vivo. Next, we explored the model interpretability and found that the learned features for target inhibition (in vitro) or cell active (in vivo) tasks are different with molecular property correlations and atom functional attentions. Based on these findings, we utilized a monte carlo based reinforcement learning generative model to generate novel multi-property compounds with both in vitro and in vivo efficacy, thus bridging the gap between target-based and cell-based drug discovery.