Thalamus-Reasoning: A Multimodal Large Language Model for Multi-Sample Omics Reasoning

Abstract

Large language models can reason over biological knowledge, but they are not naturally equipped to work with quantitative omics measurements. Existing approaches either convert expression profiles into long textual representations, often losing quantitative information, or connect omics encoders to language models for narrow tasks. We introduce Thalamus-Reasoning, a 9B multimodal language model that represents each bulk or single-cell transcriptome as a compact continuous embedding that can be interleaved with natural-language instructions and with other samples in the same context. A key contribution is a training corpus that connects experimental measurements with biological knowledge and task supervision. We combine templates linking transcriptomic profiles to annotations and experimental outcomes, reasoning examples connecting evidence across sources, and LLM-generated supervision with task-specific quality checks. The instruction-tuning corpus spans 157 biological and general-purpose task groups. Training includes continued pretraining on 20 billion tokens and supervised fine-tuning on 5.21 million conversations. We further introduce GEO-OmicsQA, a publication-disjoint benchmark of 3,000 questions requiring models to interpret and compare expression profiles from real GEO studies. Thalamus-Reasoning achieves the best results among the evaluated models on three of four held-out annotation tasks and on all six GEO-OmicsQA variants, and the best average performance among compared methods on PerturbQA perturbation-response prediction. Ablations show a clear advantage for continuous omics representations over a text-only gene-list representation. These results show that quantitative transcriptomic measurements and biological language can be integrated within a general conversational model, enabling both predictive tasks and language-guided interpretation of experimental samples.