Predicting function of evolutionarily implausible DNA sequences

Genomic language models (gLMs) show potential for generating novel, functional DNA sequences for synthetic biology, but doing so requires them to learn not just evolutionary plausibility, but also sequence-to-function relationships. We introduce a set of prediction tasks called Nullsettes, which assesses a model's ability to predict loss-of-function mutations created by translocating key control elements in synthetic expression cassettes. Across 12 state-of-the-art models, we find that mutation effect prediction performance strongly correlates with the predicted likelihood of the nonmutant. Furthermore, the range of likelihood values predictive of strong model performance is highly dependent on sequence length. Our work highlights the importance of considering both sequence likelihood and sequence length when using gLMs for mutation effect prediction.

ProjectedEx: Enhancing Generation in Explainable AI for Prostate Cancer

Prostate cancer, a growing global health concern, necessitates precise diagnostic tools, with Magnetic Resonance Imaging (MRI) offering high-resolution soft tissue imaging that significantly enhances diagnostic accuracy. Recent advancements in explainable AI and representation learning have significantly improved prostate cancer diagnosis by enabling automated and precise lesion classification. However, existing explainable AI methods, particularly those based on frameworks like generative adversarial networks (GANs), are predominantly developed for natural image generation, and their application to medical imaging often leads to suboptimal performance due to the unique characteristics and complexity of medical image. To address these challenges, our paper introduces three key contributions. First, we propose ProjectedEx, a generative framework that provides interpretable, multi-attribute explanations, effectively linking medical image features to classifier decisions. Second, we enhance the encoder module by incorporating feature pyramids, which enables multiscale feedback to refine the latent space and improves the quality of generated explanations. Additionally, we conduct comprehensive experiments on both the generator and classifier, demonstrating the clinical relevance and effectiveness of ProjectedEx in enhancing interpretability and supporting the adoption of AI in medical settings. Code will be released at https://github.com/Richardqiyi/ProjectedEx