Paula Cárdenas

Sebastian Ojeda, Rafael Velasquez, Nicolás Aparicio et al.

Antimicrobial peptides have emerged as promising molecules to combat antimicrobial resistance. However, fragmented datasets, inconsistent annotations, and the lack of standardized benchmarks hinder computational approaches and slow down the discovery of new candidates. To address these challenges, we present the Expanded Standardized Collection for Antimicrobial Peptide Evaluation (ESCAPE), an experimental framework integrating over 80.000 peptides from 27 validated repositories. Our dataset separates antimicrobial peptides from negative sequences and incorporates their functional annotations into a biologically coherent multilabel hierarchy, capturing activities across antibacterial, antifungal, antiviral, and antiparasitic classes. Building on ESCAPE, we propose a transformer-based model that leverages sequence and structural information to predict multiple functional activities of peptides. Our method achieves up to a 2.56% relative average improvement in mean Average Precision over the second-best method adapted for this task, establishing a new state-of-the-art multilabel peptide classification. ESCAPE provides a comprehensive and reproducible evaluation framework to advance AI-driven antimicrobial peptide research.

Gabriel Mejia, Daniela Ruiz, Paula Cárdenas et al.

Spatial Transcriptomics is a novel technology that aligns histology images with spatially resolved gene expression profiles. Although groundbreaking, it struggles with gene capture yielding high corruption in acquired data. Given potential applications, recent efforts have focused on predicting transcriptomic profiles solely from histology images. However, differences in databases, preprocessing techniques, and training hyperparameters hinder a fair comparison between methods. To address these challenges, we present a systematically curated and processed database collected from 26 public sources, representing an 8.6-fold increase compared to previous works. Additionally, we propose a state-of-the-art transformer based completion technique for inferring missing gene expression, which significantly boosts the performance of transcriptomic profile predictions across all datasets. Altogether, our contributions constitute the most comprehensive benchmark of gene expression prediction from histology images to date and a stepping stone for future research on spatial transcriptomics.

Daniela Ruiz, Paula Cárdenas, Leonardo Manrique et al.

Spatial Transcriptomics is a groundbreaking technology that integrates histology images with spatially resolved gene expression profiles. Among the various Spatial Transcriptomics techniques available, Visium has emerged as the most widely adopted. However, its accessibility is limited by high costs, the need for specialized expertise, and slow clinical integration. Additionally, gene capture inefficiencies lead to significant dropout, corrupting acquired data. To address these challenges, the deep learning community has explored the gene expression prediction task directly from histology images. Yet, inconsistencies in datasets, preprocessing, and training protocols hinder fair comparisons between models. To bridge this gap, we introduce SpaRED, a systematically curated database comprising 26 public datasets, providing a standardized resource for model evaluation. We further propose SpaCKLE, a state-of-the-art transformer-based gene expression completion model that reduces mean squared error by over 82.5% compared to existing approaches. Finally, we establish the SpaRED benchmark, evaluating eight state-of-the-art prediction models on both raw and SpaCKLE-completed data, demonstrating SpaCKLE substantially improves the results across all the gene expression prediction models. Altogether, our contributions constitute the most comprehensive benchmark of gene expression prediction from histology images to date and a stepping stone for future research on Spatial Transcriptomics.

Paula Cárdenas, Leonardo Manrique, Daniela Vega et al.

Computer Vision has proven to be a powerful tool for analyzing Spatial Transcriptomics (ST) data. However, current models that predict spatially resolved gene expression from histopathology images suffer from significant limitations due to data dropout. Most existing approaches rely on single-cell RNA sequencing references, making them dependent on alignment quality and external datasets while also risking batch effects and inherited dropout. In this paper, we address these limitations by introducing LGDiST, the first reference-free latent gene diffusion model for ST data dropout. We show that LGDiST outperforms the previous state-of-the-art in gene expression completion, with an average Mean Squared Error that is 18% lower across 26 datasets. Furthermore, we demonstrate that completing ST data with LGDiST improves gene expression prediction performance on six state-of-the-art methods up to 10% in MSE. A key innovation of LGDiST is using context genes previously considered uninformative to build a rich and biologically meaningful genetic latent space. Our experiments show that removing key components of LGDiST, such as the context genes, the ST latent space, and the neighbor conditioning, leads to considerable drops in performance. These findings underscore that the full architecture of LGDiST achieves substantially better performance than any of its isolated components.

Gabriel Mejia, Paula Cárdenas, Daniela Ruiz et al.

Spatial transcriptomics is an emerging technology that aligns histopathology images with spatially resolved gene expression profiling. It holds the potential for understanding many diseases but faces significant bottlenecks such as specialized equipment and domain expertise. In this work, we present SEPAL, a new model for predicting genetic profiles from visual tissue appearance. Our method exploits the biological biases of the problem by directly supervising relative differences with respect to mean expression, and leverages local visual context at every coordinate to make predictions using a graph neural network. This approach closes the gap between complete locality and complete globality in current methods. In addition, we propose a novel benchmark that aims to better define the task by following current best practices in transcriptomics and restricting the prediction variables to only those with clear spatial patterns. Our extensive evaluation in two different human breast cancer datasets indicates that SEPAL outperforms previous state-of-the-art methods and other mechanisms of including spatial context.