From Human Labels to Literature: Semi-Supervised Learning of NMR Chemical Shifts at Scale

TL;DR

This paper introduces a semi-supervised learning framework that leverages millions of literature-extracted NMR spectra without atom-level labels to improve chemical shift prediction accuracy and robustness, capturing solvent effects at scale.

Contribution

It presents a novel permutation-invariant set supervision approach with a sorting-based loss, enabling large-scale semi-supervised training from literature data, surpassing state-of-the-art methods.

Findings

Achieves higher accuracy and robustness than existing models.

Demonstrates effective generalization on diverse molecular datasets.

Captures systematic solvent effects across common NMR solvents.

Abstract

Accurate prediction of nuclear magnetic resonance (NMR) chemical shifts is fundamental to spectral analysis and molecular structure elucidation, yet existing machine learning methods rely on limited, labor-intensive atom-assigned datasets. We propose a semi-supervised framework that learns NMR chemical shifts from millions of literature-extracted spectra without explicit atom-level assignments, integrating a small amount of labeled data with large-scale unassigned spectra. We formulate chemical shift prediction from literature spectra as a permutation-invariant set supervision problem, and show that under commonly satisfied conditions on the loss function, optimal bipartite matching reduces to a sorting-based loss, enabling stable large-scale semi-supervised training beyond traditional curated datasets. Our models achieve substantially improved accuracy and robustness over state-of-the-art methods and exhibit stronger generalization on significantly larger and more diverse molecular datasets. Moreover, by incorporating solvent information at scale, our approach captures systematic solvent effects across common NMR solvents for the first time. Overall, our results demonstrate that large-scale unlabeled spectra mined from the literature can serve as a practical and effective data source for training NMR shift models, suggesting a broader role of literature-derived, weakly structured data in data-centric AI for science.