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Are You Learning Biological Signal or Shortcuts? Auditing and Mitigating Bias in Protein-Protein Interaction Datasets

arXiv · AI, language, vision and robotics · article · Sep 9, 2026 · UTC

Protein-protein interaction (PPI) databases do not faithfully reflect biological realities. Instead, they are influenced by study and technical biases that distort certain protein and interaction attributes. Machine learning models can exploit these as learning shortcuts if the negative dataset is not constructed with care. So far, the shortcuts introduced during PPI dataset construction have only been examined in isolation. Here, we systematically characterize both reported and, to our knowledge, previously unreported biases in PPI datasets that lead machine learning models to learn shortcuts

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