Abstract:Scientific discovery in digital health requires converting continuous physiological signals from wearable devices into clinically actionable biomarkers. We introduce CoDaS (AI Co-Data-Scientist), a multi-agent system that structures biomarker discovery as an iterative process combining hypothesis generation, statistical analysis, adversarial validation, and literature-grounded reasoning with human oversight using large-scale wearable datasets. Across three cohorts totaling 9,279 participant-observations, CoDaS identified 41 candidate digital biomarkers for mental health and 25 for metabolic outcomes, each subjected to an internal validation battery spanning replication, stability, robustness, and discriminative power. Across two independent depression cohorts, CoDaS surfaced circadian instability-related features in both datasets, reflected in sleep duration variability (DWB, ρ= 0.252, p < 0.001) and sleep onset variability (GLOBEM, ρ= 0.126, p < 0.001). In a metabolic cohort, CoDaS derived a cardiovascular fitness index (steps/resting heart rate; ρ= -0.374, p < 0.001), and recovered established clinical associations, including the hepatic function ratio (AST/ALT; ρ= -0.375, p < 0.001), a known correlate of insulin resistance. Incorporating CoDaS-derived features alongside demographic variables led to modest but consistent improvements in predictive performance, with cross-validated ΔR^2 increases of 0.040 for depression and 0.021 for insulin resistance. These findings suggest that CoDaS enables systematic and traceable hypothesis generation and prioritization for biomarker discovery from large-scale wearable data.
Abstract:Large language model (LLM)-based AI systems have shown promise for patient-facing diagnostic and management conversations in simulated settings. Translating these systems into clinical practice requires assessment in real-world workflows with rigorous safety oversight. We report a prospective, single-arm feasibility study of an LLM-based conversational AI, the Articulate Medical Intelligence Explorer (AMIE), conducting clinical history taking and presentation of potential diagnoses for patients to discuss with their provider at urgent care appointments at a leading academic medical center. 100 adult patients completed an AMIE text-chat interaction up to 5 days before their appointment. We sought to assess the conversational safety and quality, patient and clinician experience, and clinical reasoning capabilities compared to primary care providers (PCPs). Human safety supervisors monitored all patient-AMIE interactions in real time and did not need to intervene to stop any consultations based on pre-defined criteria. Patients reported high satisfaction and their attitudes towards AI improved after interacting with AMIE (p < 0.001). PCPs found AMIE's output useful with a positive impact on preparedness. AMIE's differential diagnosis (DDx) included the final diagnosis, per chart review 8 weeks post-encounter, in 90% of cases, with 75% top-3 accuracy. Blinded assessment of AMIE and PCP DDx and management (Mx) plans suggested similar overall DDx and Mx plan quality, without significant differences for DDx (p = 0.6) and appropriateness and safety of Mx (p = 0.1 and 1.0, respectively). PCPs outperformed AMIE in the practicality (p = 0.003) and cost effectiveness (p = 0.004) of Mx. While further research is needed, this study demonstrates the initial feasibility, safety, and user acceptance of conversational AI in a real-world setting, representing crucial steps towards clinical translation.
Abstract:Scientific discovery relies on scientists generating novel hypotheses that undergo rigorous experimental validation. To augment this process, we introduce an AI co-scientist, a multi-agent system built on Gemini 2.0. The AI co-scientist is intended to help uncover new, original knowledge and to formulate demonstrably novel research hypotheses and proposals, building upon prior evidence and aligned to scientist-provided research objectives and guidance. The system's design incorporates a generate, debate, and evolve approach to hypothesis generation, inspired by the scientific method and accelerated by scaling test-time compute. Key contributions include: (1) a multi-agent architecture with an asynchronous task execution framework for flexible compute scaling; (2) a tournament evolution process for self-improving hypotheses generation. Automated evaluations show continued benefits of test-time compute, improving hypothesis quality. While general purpose, we focus development and validation in three biomedical areas: drug repurposing, novel target discovery, and explaining mechanisms of bacterial evolution and anti-microbial resistance. For drug repurposing, the system proposes candidates with promising validation findings, including candidates for acute myeloid leukemia that show tumor inhibition in vitro at clinically applicable concentrations. For novel target discovery, the AI co-scientist proposed new epigenetic targets for liver fibrosis, validated by anti-fibrotic activity and liver cell regeneration in human hepatic organoids. Finally, the AI co-scientist recapitulated unpublished experimental results via a parallel in silico discovery of a novel gene transfer mechanism in bacterial evolution. These results, detailed in separate, co-timed reports, demonstrate the potential to augment biomedical and scientific discovery and usher an era of AI empowered scientists.