# RetroComposer: Composing Templates for Template-Based Retrosynthesis Prediction

arXiv: https://arxiv.org/abs/2112.11225 · HTML: https://mlsanity.com/paper/2112.11225/

## Key facts

- Cited by 13 papers in the map (data through 14 Oct 2026).
- Builds on 24 of its 43 references that are in the map.
- First posted on arXiv 20 Dec 2021.

## Builds on (most cited first, 24 of 24)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Batch Normalization: Accelerating Deep Network Training by Reducing Internal Covariate Shift](https://mlsanity.com/paper/1502.03167/) (2015)
- [Layer Normalization](https://mlsanity.com/paper/1607.06450/) (2016)
- [Delving Deep into Rectifiers: Surpassing Human-Level Performance on ImageNet Classification](https://mlsanity.com/paper/1502.01852/) (2015)
- [Neural Message Passing for Quantum Chemistry](https://mlsanity.com/paper/1704.01212/) (2017)
- [Fast Graph Representation Learning with PyTorch Geometric](https://mlsanity.com/paper/1903.02428/) (2019)
- [On the Properties of Neural Machine Translation: Encoder-Decoder Approaches](https://mlsanity.com/paper/1409.1259/) (2014)
- [Strategies for Pre-training Graph Neural Networks](https://mlsanity.com/paper/1905.12265/) (2019)
- [Representation Learning on Graphs with Jumping Knowledge Networks](https://mlsanity.com/paper/1806.03536/) (2018)
- [Gated Graph Sequence Neural Networks](https://mlsanity.com/paper/1511.05493/) (2015)
- [Learning to Plan Chemical Syntheses](https://mlsanity.com/paper/1708.04202/) (2017)
- [Retrosynthesis Prediction with Conditional Graph Logic Network](https://mlsanity.com/paper/2001.01408/) (2020)
- [Predicting Organic Reaction Outcomes with Weisfeiler-Lehman Network](https://mlsanity.com/paper/1709.04555/) (2017)
- [Molecule Edit Graph Attention Network: Modeling Chemical Reactions as Sequences of Graph Edits](https://mlsanity.com/paper/2006.15426/) (2020)
- [Retrosynthetic reaction prediction using neural sequence-to-sequence models](https://mlsanity.com/paper/1706.01643/) (2017)
- [A Graph to Graphs Framework for Retrosynthesis Prediction](https://mlsanity.com/paper/2003.12725/) (2020)
- [RetroXpert: Decompose Retrosynthesis Prediction like a Chemist](https://mlsanity.com/paper/2011.02893/) (2020)
- [Permutation invariant graph-to-sequence model for template-free retrosynthesis and reaction prediction](https://mlsanity.com/paper/2110.09681/) (2021)
- [Learning Graph Models for Retrosynthesis Prediction](https://mlsanity.com/paper/2006.07038/) (2020)
- [Energy-based View of Retrosynthesis](https://mlsanity.com/paper/2007.13437/) (2020)
- [Modelling Chemical Reasoning to Predict Reactions](https://mlsanity.com/paper/1608.07117/) (2016)

## Built on by (most cited first, 13 of 13)

- [Re-evaluating Retrosynthesis Algorithms with Syntheseus](https://mlsanity.com/paper/2310.19796/) (2023)
- [RetroGFN: Diverse and Feasible Retrosynthesis using GFlowNets](https://mlsanity.com/paper/2406.18739/) (2024)
- [Node-Aligned Graph-to-Graph (NAG2G): Elevating Template-Free Deep Learning Approaches in Single-Step Retrosynthesis](https://mlsanity.com/paper/2309.15798/) (2023)
- [MARS: A Motif-based Autoregressive Model for Retrosynthesis Prediction](https://mlsanity.com/paper/2209.13178/) (2022)
- [RetroDiff: Retrosynthesis as Multi-stage Distribution Interpolation](https://mlsanity.com/paper/2311.14077/) (2023)
- [RCsearcher: Reaction Center Identification in Retrosynthesis via Deep Q-Learning](https://mlsanity.com/paper/2301.12071/) (2023)
- [TempRe: Template generation for single and direct multi-step retrosynthesis](https://mlsanity.com/paper/2507.21762/) (2025)
- [A Unified View of Deep Learning for Reaction and Retrosynthesis Prediction: Current Status and Future Challenges](https://mlsanity.com/paper/2306.15890/) (2023)
- [Survey on Recent Progress of AI for Chemistry: Methods, Applications, and Opportunities](https://mlsanity.com/paper/2502.17456/) (2025)
- [Evolutionary Retrosynthetic Route Planning](https://mlsanity.com/paper/2310.05186/) (2023)
- [Retrosynthesis Prediction via Search in (Hyper) Graph](https://mlsanity.com/paper/2402.06772/) (2024)
- [Accurate, Interdisciplinary and Transparent Structure-property Understanding with Deep Native Structural Reasoning](https://mlsanity.com/paper/2607.07708/) (2026)
- [A Transformer Model for Predicting Chemical Products from Generic SMARTS Templates with Data Augmentation](https://mlsanity.com/paper/2503.05810/) (2025)

## Abstract (arXiv)

The main target of retrosynthesis is to recursively decompose desired molecules into available building blocks. Existing template-based retrosynthesis methods follow a template selection stereotype and suffer from limited training templates, which prevents them from discovering novel reactions. To overcome this limitation, we propose an innovative retrosynthesis prediction framework that can compose novel templates beyond training templates. As far as we know, this is the first method that uses machine learning to compose reaction templates for retrosynthesis prediction. Besides, we propose an effective reactant candidate scoring model that can capture atom-level transformations, which helps our method outperform previous methods on the USPTO-50K dataset. Experimental results show that our method can produce novel templates for 15 USPTO-50K test reactions that are not covered by training templates. We have released our source implementation.