Significance and Stability Analysis of Genotype-Environment Interaction using GxEStat

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.

The rapid development of generative models for single-cell gene expression data has created an urgent need for standardised evaluation frameworks. Current evaluation practices suffer from inconsistent metric implementations, incomparable hyperparameter choices, and a lack of biologically-grounded metrics. We present Generated Genetic Expression Evaluator (GGE), an open-source Python framework that addresses these challenges by providing a comprehensive suite of distributional metrics with explicit computation space options and biologically-motivated evaluation through differentially expressed gene (DEG)-focused analysis and perturbation-effect correlation, enabling standardized reporting and reproducible benchmarking. Through extensive analysis of the single-cell generative modeling literature, we identify that no standardized evaluation protocol exists. Methods report incomparable metrics computed in different spaces with different hyperparameters. We demonstrate that metric values vary substantially depending on implementation choices, highlighting the critical need for standardization. GGE enables fair comparison across generative approaches and accelerates progress in perturbation response prediction, cellular identity modeling, and counterfactual inference.

Behavioral phenotyping of genetic animal models currently requires labor-intensive manual feature engineering that limits reproducibility and scalability. We present GEESE, an end-to-end deep learning framework that learns behavioral representations directly from 3D pose dynamics without hand-crafted features. Using a pretrained time series foundation model, we encode movement sequences into a behavioral manifold that supports both behavior classification and genotype prediction. Evaluated across three autism-associated genetic models (CNTNAP2, CHD8, FMR1), our deep learning approach surpasses hand-crafted feature baselines in both tasks, revealing that learned representations capture genotype-specific behavioral signatures. The framework generalizes across genetic backgrounds, and an all-cohort model identifies both genetic background and genotype from movement patterns alone. We further provide HONK, an interactive intelligent tool enabling researchers without programming expertise to perform behavioral phenotyping from pose data through natural language interaction.