Large language model-assisted discovery of cohorts from scientific literature

Background: Planning multi-study analyses requires identifying cohorts with the relevant participants, phenotypes, and data modalities. This process commonly relies on prior knowledge, cohort catalogues, and manual literature searches. We developed a complementary question-driven framework that searches relevant scientific literature and extracts explicit cohort names. Methods: The framework first generates multiple PubMed queries from configurable vocabularies and templates and retrieves the resulting scientific literature automatically through the PubMed API. A large language model then screens the retrieved titles and abstracts and extracts explicit cohort names using a prompt tailored to the research question. The extracted names are deduplicated with human review. Configurable code, prompts, and example outputs are available at https://gitlab.rz.uni-frankfurt.de/cap_molgenlab/literature-cohort-discovery. Evaluation: As a use case, we applied the framework to youth aggression genetics. From 5,400 generated PubMed queries, the framework retrieved 5,254 unique records and identified 188 candidate cohorts. Manual screening using predefined criteria, including participant age and genetic-data availability, retained 44 eligible cohorts. Automated LLM-based name extraction was within the agreement range of human annotators. We also searched four established cohort catalogues using the same research question. Their combined results contained 27 of the 44 eligible cohorts, while 17 were not returned by any cohort catalogue search. Conclusion: The framework converts research-question-specific vocabulary into screenable cohort inventories via a large, automated literature search. It can be adapted across populations, phenotypes, data modalities, and study designs, and provides a literature-based complement to curated cohort catalogues.

CALM: Interpretable Cross-Modal Alignment for Biomarker Discovery from Unpaired Data

The interaction between brain structure and genetic influences is key to understanding neuropsychiatric disorders. However, most large-scale datasets are unimodal, providing either neuroimaging or genetics data. We propose CALM, a framework that learns interpretable associations between brain ROIs and genetic pathways from completely disjoint populations. CALM aligns the two modalities in a shared latent space via linear projections that simultaneously match the class-conditional latent distributions and ensure group separability. These projections provide interpretable pathway--ROI associations. When trained on unimodal imaging and genetics datasets, CALM generalizes to an unseen paired dataset, outperforming several state-of-the-art methods and ablation baselines. We also demonstrate stability of the learned associations against a paired baseline. Our experiments on autism spectrum disorder reveal immune and metabolic pathways linked to specific cortical regions and are consistent with established literature. Thus, CALM opens the door to leveraging large unimodal repositories for studying cross-modal interactions in brain disorders across disparate datasets.