Learning Invariant Molecular Representation in Latent Discrete Space
Xiang Zhuang Qiang Zhang Keyan Ding Yatao Bian Xiao Wang Jingsong Lv Hongyang Chen Huajun Chen
Molecular representation learning lays the foundation for drug discovery.
However, existing methods suffer from poor out-of-distribution (OOD)
generalization, particularly when data for training and testing originate from
different environments. To address this issue, we propose a new framework for
learning molecular representations that exhibit invariance and robustness
against distribution shifts. Specifically, we propose a strategy called
``first-encoding-then-separation'' to identify invariant molecule features in
the latent space, which deviates from conventional practices. Prior to the
separation step, we introduce a residual vector quantization module that
mitigates the over-fitting to training data distributions while preserving the
expressivity of encoders. Furthermore, we design a task-agnostic
self-supervised learning objective to encourage precise invariance
identification, which enables our method widely applicable to a variety of
tasks, such as regression and multi-label classification. Extensive experiments
on 18 real-world molecular datasets demonstrate that our model achieves
stronger generalization against state-of-the-art baselines in the presence of
various distribution shifts. Our code is available at
https://github.com/HICAI-ZJU/iMoLD.