ResGene-T: A Tensor-Based Residual Network Approach for Genomic Prediction

Deep neural networks have achieved strong performance in genomic sequence classification; however, relating their predictions to biologically meaningful sequence patterns remains challenging. In this work, we present AttnGen, an attention-guided training framework that embeds interpretability directly into the optimization process. AttnGen computes nucleotide-level importance scores using an attention mechanism and progressively suppresses low-contribution positions during training. This encourages the model to focus its predictions on a compact set of informative regions while reducing reliance on noisy sequence elements. We evaluate AttnGen on the standardized demo_human_or_worm benchmark, a binary classification task over 200-nucleotide sequences. With moderate masking, AttnGen achieves a validation accuracy of 96.73%, outperforming a conventional CNN baseline with 95.83% accuracy, while also exhibiting faster convergence and improved training stability. To assess whether the learned importance scores reflect functionally relevant signal, we conduct perturbation-based analysis by removing high-saliency nucleotides. This causes accuracy to drop from 96.9% to near chance level on a 3,000-sequence evaluation set, indicating that the model relies on a relatively small subset of informative positions. Our analysis shows that masking 10--20% of positions provides the most favorable trade-off between predictive performance and interpretability. These results suggest that attention-guided masking not only improves classification performance but also reshapes how models distribute importance across sequence positions. Although this study focuses on short genomic sequences, the proposed approach may extend to more complex interpretable sequence modeling settings.

Genomic Foundation Models (GFMs) typically rely on Masked Language Modeling (MLM) or Next-Token Prediction (NTP) to learn the "Laws of Nature". While effective at capturing local syntax, these generative paradigms prioritize token-level reconstruction over high-level functional context. We introduce JEPA-DNA, a model-agnostic continual training framework that integrates a Joint-Embedding Predictive Architecture (JEPA) with traditional generative objectives. By supervising global sequence embeddings in a latent space, JEPA-DNA forces models to predict the functional representations of masked genomic segments, shifting the learning signal from token recovery to semantic alignment. We evaluate JEPA-DNA on 17 diverse genomic benchmark tasks, demonstrating consistent gains in linear probing and zero-shot performance regardless of the underlying GFM architecture or generative objective. Our framework establishes a new state-of-the-art for GFMs, surpassing the best existing models by bridging generative precision with latent semantic grounding. Through extensive ablation studies, we further characterize the synergistic interplay between generative and latent objectives. Our code is publicly available at https://github.com/NVIDIA-Digital-Bio/JEPA-DNA.

Robust genotype-to-phenotype (G2P) prediction is essential for accelerating breeding decisions and genetic gain. However, it remains challenging to measure complex traits under variable field conditions and across years. In this study, we propose a linear-Transformer approach, LiT-G2P (Linear-Transformer Genotype-to-Phenotype), an automated predictive framework that integrates additive genetic variance effects with Transformer-based nonlinear interactions using genome-wide single-nucleotide polymorphisms (SNPs) data. We evaluated LiT-G2P on a panel of diverse grape accessions, genotyped with SNP markers and measured for phenotypes across two consecutive years. Target phenotypic traits include leaf hair density and trichome density of grapevines. Across both single-year and cross-year testing scenarios, LiT-G2P consistently improves prediction performance compared with baseline models. For hair density, LiT-G2P achieves the lowest error in both single-year and cross-year evaluations, with RMSEs of 0.469 and 0.454, respectively, while maintaining strong tolerance accuracies of 79.2% and 74.6%, respectively. For trichome density, LiT-G2P also presents the best overall G2P performance. In addition, we extract model-prioritized SNPs from attention weights and apply genotype-stratified analysis to provide interpretable candidate marker for downstream validation. These results demonstrate that integrating stable additive effects with learned interaction patterns can enhance cross-year robustness and support practical SNP-based predictive modeling for genomic selection.