Removing Biases from Molecular Representations via Information Maximization

High-throughput drug screening - using cell imaging or gene expression measurements as readouts of drug effect - is a critical tool in biotechnology to assess and understand the relationship between the chemical structure and biological activity of a drug. Since large-scale screens have to be divided into multiple experiments, a key difficulty is dealing with batch effects, which can introduce systematic errors and non-biological associations in the data. We propose InfoCORE, an Information maximization approach for COnfounder REmoval, to effectively deal with batch effects and obtain refined molecular representations. InfoCORE establishes a variational lower bound on the conditional mutual information of the latent representations given a batch identifier. It adaptively reweighs samples to equalize their implied batch distribution. Extensive experiments on drug screening data reveal InfoCORE's superior performance in a multitude of tasks including molecular property prediction and molecule-phenotype retrieval. Additionally, we show results for how InfoCORE offers a versatile framework and resolves general distribution shifts and issues of data fairness by minimizing correlation with spurious features or removing sensitive attributes. Representation learning (Bengio et al., 2013) has become pivotal in drug discovery (Wu et al., 2018) and understanding biological systems (Yang et al., 2021b). It serves as a pillar for recognizing drug mechanisms, predicting a drug's activity and toxicity, and identifying disease-associated chemical structures. A central challenge in this context is to accurately capture the nuanced relationship between the chemical structure of a small molecule and its biological or physical attributes. Most molecular representation learning methods only encode a molecule's chemical identity and hence provide unimodal representations (Wang et al., 2022; Xu et al., 2021b). A limitation of such techniques is that molecules with similar structures can have very different effects in the cellular context.