# Chemical knowledge-informed framework for privacy-aware retrosynthesis learning

arXiv: https://arxiv.org/abs/2502.19119 · HTML: https://mlsanity.com/paper/2502.19119/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 40 of its 94 references that are in the map.
- First posted on arXiv 26 Feb 2025.

## Builds on (most cited first, 30 of 40)

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- [Sequence to Sequence Learning with Neural Networks](https://mlsanity.com/paper/1409.3215/) (2014)
- [Deep Learning with Differential Privacy](https://mlsanity.com/paper/1607.00133/) (2016)
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- [Beam Search Strategies for Neural Machine Translation](https://mlsanity.com/paper/1702.01806/) (2017)
- [Molecular Transformer - A Model for Uncertainty-Calibrated Chemical Reaction Prediction](https://mlsanity.com/paper/1811.02633/) (2018)
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- [On the Convergence of A Class of Adam-Type Algorithms for Non-Convex Optimization](https://mlsanity.com/paper/1808.02941/) (2018)
- [Privacy and Robustness in Federated Learning: Attacks and Defenses](https://mlsanity.com/paper/2012.06337/) (2020)
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- [Mini-batch Stochastic Approximation Methods for Nonconvex Stochastic Composite Optimization](https://mlsanity.com/paper/1308.6594/) (2013)
- [Salvaging Federated Learning by Local Adaptation](https://mlsanity.com/paper/2002.04758/) (2020)
- [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)
- [Provable Defense against Privacy Leakage in Federated Learning from Representation Perspective](https://mlsanity.com/paper/2012.06043/) (2020)
- [Molecule Edit Graph Attention Network: Modeling Chemical Reactions as Sequences of Graph Edits](https://mlsanity.com/paper/2006.15426/) (2020)
- [MedPerf: Open Benchmarking Platform for Medical Artificial Intelligence using Federated Evaluation](https://mlsanity.com/paper/2110.01406/) (2021)
- [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)
- [FedNLP: Benchmarking Federated Learning Methods for Natural Language Processing Tasks](https://mlsanity.com/paper/2104.08815/) (2021)
- [Mapping the Space of Chemical Reactions Using Attention-Based Neural Networks](https://mlsanity.com/paper/2012.06051/) (2020)
- [RetroXpert: Decompose Retrosynthesis Prediction like a Chemist](https://mlsanity.com/paper/2011.02893/) (2020)

## Abstract (arXiv)

Chemical reaction data is a pivotal asset, driving advances in competitive fields such as pharmaceuticals, materials science, and industrial chemistry. Its proprietary nature renders it sensitive, as it often includes confidential insights and competitive advantages organizations strive to protect. However, in contrast to this need for confidentiality, the current standard training paradigm for machine learning-based retrosynthesis gathers reaction data from multiple sources into one single edge to train prediction models. This paradigm poses considerable privacy risks as it necessitates broad data availability across organizational boundaries and frequent data transmission between entities, potentially exposing proprietary information to unauthorized access or interception during storage and transfer. In the present study, we introduce the chemical knowledge-informed framework (CKIF), a privacy-preserving approach for learning retrosynthesis models. CKIF enables distributed training across multiple chemical organizations without compromising the confidentiality of proprietary reaction data. Instead of gathering raw reaction data, CKIF learns retrosynthesis models through iterative, chemical knowledge-informed aggregation of model parameters. In particular, the chemical properties of predicted reactants are leveraged to quantitatively assess the observable behaviors of individual models, which in turn determines the adaptive weights used for model aggregation. On a variety of reaction datasets, CKIF outperforms several strong baselines by a clear margin.