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Giunchiglia, V.

Publications and source records attributed to Giunchiglia, V..

2 recordsLinked to original sources

Medea: An omics AI agent for therapeutic discovery

Therapeutic hypotheses can transfer across diseases but their relevance depends on biological context. The same target, perturbation, or treatment can produce different effects across cell types, disease states, genetic backgrounds, and patients. Therapeutic reasoning therefore requires methods that preserve context, test when evidence supports transfer, and identify where context-specific effects limit it. Although AI agents can perform therapeutic analyses, existing systems often fail to preserve biological context over long workflows, verify intermediate computational steps, or reconcile conflicting evidence across datasets and literature. Here, we present Medea, an AI agent for therapeutic reasoning across biological contexts. Medea executes multi-step analyses using biological tools, machine learning models, and literature retrieval while enforcing verification during planning, execution, and evidence synthesis. We evaluate Medea across 5,673 open-ended analyses in three domains: cell type specific therapeutic target nomination in five diseases and 29 cell types, synthetic lethality prediction in 7 cancer cell lines, and immunotherapy response prediction from multimodal patient profiles. Using a previously unpublished epistatic miniarray profiling screen performed under two DNA-damaging treatments, we evaluate Medea on predicting synthetic lethality among 238,046 gene-gene pairs in yeast. Medea predicts these experimentally measured synthetic lethal interactions, indicating that its performance reflects biological relevance rather than information leakage from benchmark datasets. Across these evaluations, Medea improves performance over large language models, reasoning models, biomedical agents, and specialized machine learning models while maintaining low failure rates and calibrated abstention. These results show that verifiable AI agents can perform therapeutic analyses across biological contexts.

bioinformatics↗

ProCyon: A multimodal foundation model for protein phenotypes

Characterizing human proteins remains a major challenge: approximately 29% of human proteins lack experimentally validated functions and even well-annotated proteins often lack context-specific phenotypic insights. To enable universal modeling of protein phenotypes, we present PO_SCPLOWROC_SCPLOWCO_SCPLOWYONC_SCPLOW, a multimodal foundation model that utilizes protein sequence, structure, and natural language for generating and predicting protein phenotypes across diverse knowledge domains. PO_SCPLOWROC_SCPLOWCO_SCPLOWYONC_SCPLOW is trained on our novel dataset, PO_SCPLOWROC_SCPLOWCO_SCPLOWYONC_SCPLOW-IO_SCPLOWNSTRUCTC_SCPLOW, with 33 million protein phenotype instructions. On dozens of benchmarking tasks, PO_SCPLOWROC_SCPLOWCO_SCPLOWYONC_SCPLOW performs competitively against single-modal and multimodal models. Further, PO_SCPLOWROC_SCPLOWCO_SCPLOWYONC_SCPLOW conditionally retrieves proteins via mechanisms of action of small molecule drugs and disease contexts, and it generates candidate phenotypic descriptions for poorly characterized proteins, including those implicated in Parkinsons disease that were identified after PO_SCPLOWROC_SCPLOWCO_SCPLOWYONC_SCPLOWs knowledge cutoff date. We experimentally confirm PO_SCPLOWROC_SCPLOWCO_SCPLOWYONC_SCPLOWs predictions in multiple sclerosis using post-mortem brain RNA-seq, identifying novel MS genes and elucidating associated pathway mechanisms consistent with cortical pathology. PO_SCPLOWROC_SCPLOWCO_SCPLOWYONC_SCPLOW paves the way toward a general approach to generate functional insights into the human proteome.

bioinformatics↗