Jordan Bryan

Hongqian Niu, Jordan Bryan, Xihao Li et al.

Recent advances in large language model (LLM) embeddings have enabled powerful representations for biological data, but most applications to date focus only on gene-level information. We present one of the first systematic frameworks to generate variant-level embeddings across the entire human genome. Using curated annotations from FAVOR, ClinVar, and the GWAS Catalog, we constructed semantic text descriptions for 8.9 billion possible variants and generated embeddings at three scales: 1.5 million HapMap3+MEGA variants, ~90 million imputed UK Biobank variants, and ~9 billion all possible variants. Embeddings were produced with both OpenAI's text-embedding-3-large and the open-source Qwen3-Embedding-0.6B models. Baseline experiments demonstrate high predictive accuracy for variant properties, validating the embeddings as structured representations of genomic variation. We outline two downstream applications: embedding-informed hypothesis testing by extending the Frequentist And Bayesian framework to genome-wide association studies, and embedding-augmented genetic risk prediction that enhances standard polygenic risk scores. These resources, publicly available on Hugging Face, provide a foundation for advancing large-scale genomic discovery and precision medicine.

Lester Mackey, Jordan Bryan, Man Yue Mo

We introduce a minorization-maximization approach to optimizing common measures of discovery significance in high energy physics. The approach alternates between solving a weighted binary classification problem and updating class weights in a simple, closed-form manner. Moreover, an argument based on convex duality shows that an improvement in weighted classification error on any round yields a commensurate improvement in discovery significance. We complement our derivation with experimental results from the 2014 Higgs boson machine learning challenge.