Tugolukova, E. | bioRxiv Science

bioRxiv2025

Queryome: Orchestrating Retrieval, Reasoning, and Synthesis across Biomedical Literature

The rapid expansion of biomedical literature has made comprehensive manual synthesis increasingly difficult to perform effectively, creating a pressing need for AI systems capable of reasoning across verified evidence rather than merely retrieving it. However, existing retrieval-augmented generation (RAG) methods often fall short when faced with complex biomedical questions that require iterative reasoning and multi-step synthesis. Here, we developed Queryome, a deep research system consisting of specialized large language model (LLM) agents that can adapt their orchestration dynamically to a wide range of queries. Using a hybrid semantic-lexical retrieval engine spanning 28.3 million PubMed abstracts, it performs iterative, evidence-grounded synthesis. On the MIRAGE benchmark, Queryome achieved 88.98 % accuracy, surpassing prior systems by up to 14 points, and improved reasoning accuracy on the biomedical Humans Last Exam (HLE) subset from 15.8% to 19.3%. Moreover, in a task for constructing a review article, it earned the highest composite score in comparison with Deep Research from OpenAI, Google, Perplexity, and Scite.AI, reflecting its strong literature retrieval and synthesis capabilities.

bioinformatics↗

bioRxiv2025

Blind Prediction of Complex Water and Ion Ensembles Around RNA in CASP16

Biomolecules rely on water and ions for stable folding, but these interactions are often transient, dynamic, or disordered and thus hidden from experiments and evaluation challenges that represent biomolecules as single, ordered structures. Here, we compare blindly predicted ensembles of water and ion structure to the cryo-EM densities observed around the Tetrahymena ribozyme at 2.2-2.3 [A] resolution, collected through target R1260 in the CASP16 competition. 26 groups participated in this solvation cryo-ensemble prediction challenge, submitting over 350 million atoms in total, offering the first opportunity to compare blind predictions of dynamic solvent shell ensembles to cryo-EM density. Predicted atomic ensembles were converted to density through local alignment and these densities were compared to the cryo-EM densities using Pearson correlation, Spearman correlation, mutual information, and precision-recall curves. These predictions show that an ensemble representation is able to capture information of transient or dynamic water and ions better than traditional atomic models, but there remains a large accuracy gap to the performance ceiling set by experimental uncertainty. Overall, molecular dynamics approaches best matched the cryo-EM density, with blind predictions from bussilab_plain_md, SoutheRNA, bussilab_replex, coogs2, and coogs3 outperforming the baseline molecular dynamics prediction. This study indicates that simulations of water and ions can be quantitatively evaluated with cryo-EM maps. We propose that further community-wide blind challenges can drive and evaluate progress in modeling water, ions and other previously hidden components of biomolecular systems.

biophysics↗