The advent of high-throughput sequencing has led to an exponential increase in genomic data, highlighting the need for efficient and accurate models to analyze and interpret this information. In this study, we introduce a novel, exomic foundational model that leverages a combination of the human reference genome and multispecies data to improve variant detection and interpretation. Our model utilizes a short-range transformer architecture and is trained on a large dataset of human exomic sequences derived from the Tapestry study. Through a series of ablation studies and scaling experiments, we demonstrate the effectiveness of our model in predicting next token accuracy and identifying clinically pathogenic variants. We also show that our model outperforms existing models in a range of downstream tasks, including variant effect prediction and disease state identification. In fact, our largest sequence transformer for range adaptive nucleotide decoding variant (1B parameters) surpassed previous benchmarks, demonstrating a mean accuracy of 0.880 [an 8.2% improvement over the original nucleotide transformer (NT) and a 7% improvement over NT-v2]. Furthermore, we construct a unique exomic ClinVar dataset to evaluate the model's performance on pathogenicity and disease states. Our results highlight the potential of this model to improve our understanding of the human exome and its role in disease. The model and its applications have significant implications for genomics-based diagnosis and personalized medicine, including tailored therapeutic development.

The goal of spatially explainable artificial intelligence (AI) classification approach is to build a classifier to distinguish two classes (e.g., responder, non-responder) based on the their spatial arrangements (e.g., spatial interactions between different point categories) given multi-category point data from two classes. This problem is important for generating hypotheses towards discovering new immunotherapies for cancer treatment as well as for other applications in biomedical research and microbial ecology. This problem is challenging due to an exponential number of category subsets which may vary in the strength of their spatial interactions. Most prior efforts on using human selected spatial association measures may not be sufficient for capturing the relevant spatial interactions (e.g., surrounded by) which may be of biological significance. In addition, the related deep neural networks are limited to category pairs and do not explore larger subsets of point categories. To overcome these limitations, we propose a Spatial-interaction Aware Multi-Category deep neural Network (SAMCNet) architecture and contribute novel local reference frame characterization and point pair prioritization layers for spatially explainable classification. Experimental results on multiple cancer datasets (e.g., MxIF) show that the proposed architecture provides higher prediction accuracy over baseline methods. A real-world case study demonstrates that the proposed work discovers patterns that are missed by the existing methods and has the potential to inspire new scientific discoveries.

Spatial variability is a prominent feature of various geographic phenomena such as climatic zones, USDA plant hardiness zones, and terrestrial habitat types (e.g., forest, grasslands, wetlands, and deserts). However, current deep learning methods follow a spatial-one-size-fits-all (OSFA) approach to train single deep neural network models that do not account for spatial variability. Quantification of spatial variability can be challenging due to the influence of many geophysical factors. In preliminary work, we proposed a spatial variability aware neural network (SVANN-I, formerly calledSVANN) approach where weights are a function of location but the neural network architecture is location independent. In this work, we explore a more flexible SVANN-E approach where neural network architecture varies across geographic locations. In addition, we provide a taxonomy of SVANN types and a physics inspired interpretation model. Experiments with aerial imagery based wetland mapping show that SVANN-I outperforms OSFA and SVANN-E performs the best of all.