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Removing Biases from Molecular Representations via Information Maximization (2312.00718v1)

Published 1 Dec 2023 in cs.LG, cs.AI, and q-bio.BM

Abstract: 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. The code is available at https://github.com/uhlerlab/InfoCORE.

Citations (3)

Summary

  • The paper's main contribution is introducing the InfoCORE framework which uses conditional mutual information maximization to mitigate batch effect biases in drug screening datasets.
  • The authors validate InfoCORE by demonstrating improved molecular property prediction and molecule-phenotype retrieval compared to standard methods.
  • The approach enhances robustness in molecular embeddings and offers potential for broader applications in machine learning fairness and representation learning.

Removing Biases from Molecular Representations via Information Maximization

The paper "Removing Biases from Molecular Representations via Information Maximization" presents a novel strategy designed to enhance molecular representation learning by mitigating biases, particularly those introduced by batch effects in high-throughput drug screening datasets. The method, referred to as InfoCORE (Information maximization approach for COnfounder REmoval), integrates information-theoretic concepts to tackle systematic errors resulting from batch effects, ensuring more robust and accurate molecular representation for downstream tasks such as drug activity prediction.

Key Contributions

The principal innovation of this paper lies in the introduction of InfoCORE, which leverages a variational lower bound on conditional mutual information to mitigate confounding variables like batch effects inherent in large-scale drug screening data. The concept revolves around reweighting samples to even out the distribution across batches, thus prioritizing informative features over spurious batch-related artifacts in molecular representations.

The authors employ extensive experimental validations using drug screening data, demonstrating the superior performance of InfoCORE in several key tasks: molecular property prediction and molecule-phenotype retrieval. These results underline its capability to refine molecular embeddings in a manner that is less susceptible to confounding influences, with implications for improving data fairness and resolving distribution shifts across datasets.

Theoretical and Practical Implications

On a theoretical level, InfoCORE contributes by formulating and demonstrating the efficacy of using conditional mutual information maximization within the framework of contrastive learning to debias molecular representations. This bridges a gap in contrastive learning applications, typically focused on unimodal datasets, by extending it to complex multimodal frameworks with confounding factors like batch effects.

Practically, the framework offers a versatile tool for drug discovery, as it improves the generalization of models across varying experimental conditions and enhances the robustness of predictions regarding drug activities. Furthermore, the authors suggest that this approach can be generalized beyond the immediate application of drug discovery to tackle fairness challenges in various machine learning contexts.

Future Directions

While the paper focuses on drug screening datasets, the implications of InfoCORE suggest potential extension into other areas where representation learning is challenged by confounding variables or where particular attributes lead to biased model outcomes. Future developments might include fine-tuning the InfoCORE approach to adapt to continuous rather than categorical confounders or applying the strategy to other high-dimensional biological data types.

In summary, this paper presents substantive improvements in molecular representation learning through innovative application of information-theoretic principles, with significant implications for addressing biases introduced by batch effects in drug screening data. It sets the stage for future work exploring the general applicability of similar strategies across broader AI domains concerned with fairness and robustness in machine learning models.

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