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Artificial intelligence agents and agentic artificial intelligence applied to precision medicine.

Precision medicine seeks to individualise care by integrating multimodal biomedical data, yet most deployed clinical artificial intelligence (AI) remains assistive, providing predictions without managing workflows or adapting autonomously. Agentic AI, built on large language models (LLMs), has emerged as a paradigm characterised by autonomy, goal-directed reasoning, memory, planning and tool use. This review synthesises evidence on agentic AI and LLMs applied to precision medicine, encompassing drug discovery, genomics, oncology, rare disease diagnostics and clinical pharmacology. This review also examines architectural components, recent validation milestones and emerging challenges, including hallucination, sociodemographic bias and evolving regulatory frameworks across the FDA, the EU AI Act and the WHO.

agentic AI

ELISA (Embedding-Linked Interactive Single-cell Agent): an interpretable hybrid generative Artificial Intelligence agent for expression-grounded discovery in single-cell genomics.

Translating single-cell RNA sequencing (scRNA-seq) data into mechanistic biological hypotheses remains a critical bottleneck, as agentic AI systems lack direct access to transcriptomic representations while expression foundation models remain opaque to natural language. Here, we introduce ELISA (Embedding-Linked Interactive Single-cell Agent), an interpretable framework that unifies single-cell generative pretrained transformer expression embeddings with biomedical bidirectional encoder representations from transformers-based semantic retrieval and large-language model (LLM)-mediated interpretation for interactive single-cell discovery. An automatic query classifier routes inputs to gene marker scoring, semantic matching, or reciprocal rank fusion pipelines depending on whether the query is a gene signature, natural language concept, or mixture of both. Integrated analytical modules perform pathway activity scoring across 60+ gene sets, ligand-receptor interaction prediction using 280+ curated pairs, condition-aware comparative analysis, and cell-type proportion estimation, all operating directly on embedded data without access to the original count matrix. Benchmarked across six diverse scRNA-seq datasets spanning inflammatory lung disease, pediatric and adult cancers, organoid models, healthy tissue, and neurodevelopment, ELISA significantly outperforms CellWhisperer, a classical lexical retriever (BM25), and a random baseline in cell type retrieval (combined permutation test, $p < 2\times 10^{-5}$ for each), with particularly large gains on gene-signature queries (Cohen's $d = 5.98$ for mean reciprocal rank). ELISA replicates published biological findings (mean composite score 0.88), and generates candidate hypotheses through grounded LLM reasoning, bridging the gap between transcriptomic data exploration and biological discovery.

Generative Artificial Intelligence

AI-HOPE: an AI-driven conversational agent for enhanced clinical and genomic data integration in precision medicine research.

MOTIVATION: The growing complexity of clinical cancer research has fueled a surge in demand for automated bioinformatics tools capable of integrating clinical and genomic data to accelerate discovery efforts. RESULTS: We present the Artificial Intelligence Agent for High-Optimization and Precision Medicine (AI-HOPE), an AI-driven system that enables domain experts to conduct integrative data analyses through natural language interactions. Powered by Large Language Models, AI-HOPE interprets user instructions, converts them into executable code, and autonomously analyzes locally stored data. It supports flexible association studies, subset comparisons, clinical prevalence assessments and survival analyses. In addition, AI-HOPE enables global variable scans to identify features significantly associated with a user-defined outcome, making a powerful and intuitive tool for advancing precision medicine research. Importantly, its closed-system design prevents clinical data leakage. To demonstrate its utility, AI-HOPE was applied to The Cancer Genome Atlas data to address two clinical questions. First, it identified significant enrichment of TP53 mutations in late-stage colorectal cancer compared to early-stage cases. Second, it uncovered a strong association between KRAS mutations and poorer progression-free survival in FOLFOX-treated patients. These findings align with established literature and demonstrate AI-HOPE's ability to generate meaningful insights independently, without prior assumptions. By removing programming barriers and simplifying complex analyses, AI-HOPE bridges the gap between data complexity and research needs. With its scalable and adaptable framework, AI-HOPE has the potential to support diverse biomedical research fields, driving innovation and efficiency in translational studies. AVAILABILITY AND IMPLEMENTATION: The AI-HOPE software and demonstration data is available at https://github.com/Velazquez-Villarreal-Lab/AI-HOPE.

Precision Medicine

Reimagining research papers as interactive and reliable AI agents.

Here we introduce Paper2Agent, an automated framework that converts research papers into artificial intelligence (AI) agents. Paper2Agent transforms research output from passive artefacts into active systems that accelerate use and discovery. Conventional research papers require readers to understand and adapt the paper's code, data and methods to their work, creating barriers to dissemination and reuse. Paper2Agent addresses this challenge by converting a paper into an AI agent that functions as a virtual corresponding author, exposing its manuscript, supplementary materials, datasets, code and workflows as active, agent-native knowledge rather than static text. It analyses the paper and codebase using multiple agents to construct a model context protocol (MCP) server, then generates and runs tests to refine and increase robustness of the MCP. These paper MCPs can be connected to a chat agent (such as Claude Code) to carry out complex scientific queries through natural language while invoking tools and workflows from the paper. We demonstrate Paper2Agent's effectiveness through case studies. Paper2Agent created an agent that leveraged AlphaGenome1 to interpret genomic variants and agents based on Scanpy2 and TISSUE&#xa0;(transcript imputation with spatial single-cell uncertainty estimation)3 to conduct single-cell and spatial transcriptomics analyses. We validate that these agents reproduce the results of the original papers and carry out novel user queries. Paper2Agent created multiple agents that collaborate to prioritize a causal gene for psoriasis. By turning static papers into interactive AI agents, Paper2Agent introduces a paradigm for knowledge dissemination and a collaborative ecosystem of AI co-scientists.

Journal Article

Agentic AI for Spatial Omics.

This highlight summarises recent advances in agentic artificial intelligence (AI) systems for spatial omics analysis. These systems are compared along two central tensions: autonomy versus accountability, and adaptability versus reproducibility. We argue that progress will depend not on maximising automation, but on defining where autonomy is appropriate.

Artificial Intelligence

Trustworthy Agentic AI in Bioinformatics: From Workflow Automation to Traceable and Validated Biological Inference.

Agentic artificial intelligence is extending bioinformatics beyond conversational assistance by enabling systems to select tools, execute code, revise analytical plans, and interpret biological data. These capabilities may accelerate research, but they also redistribute decisions that determine whether biological conclusions are valid. We conducted a targeted, structured PubMed search in July 2026 and identified 11 peer-reviewed agentic bioinformatics systems for descriptive review based on predefined eligibility criteria for analytical decision-making, tool or code execution, iterative evaluation, or coordinated agent activity. The evidence base covered single-cell transcriptomics, microbial genomics, cancer genomics, and omics applications, together with methodological literature on reproducibility and biological validation. We examined how current systems report delegated authority, provenance, validation, evidence, abstention, and human oversight. Existing platforms implement safeguards such as sandboxed execution, restricted commands, interaction logs, evidence identifiers, automated checks, critic agents, quality scores, and expert assessment. However, published reports rarely provide a connected account linking the original biological question to samples, reference resources, analytical decisions, computational actions, statistical results, supporting evidence, validation outcomes, and final claims. We distinguish inherited bioinformatics errors, errors amplified through autonomous action, and emergent failures arising from memory, retrieval, tool interaction, or agent coordination. We further propose a multidimensional decision-rights profile, consequence-sensitive validation gates, and a claim-to-evidence provenance architecture organized through the Traceable History of Research Evidence, Agent Actions, and Decisions in Bioinformatics (THREAD-Bio) framework. Illustrative cases show that technically successful execution may still support misleading inference. Trustworthy agentic bioinformatics therefore requires claims to remain reconstructible, challengeable, validated, and proportionate to the evidence.

accountable autonomy

Environmental antibiotic contamination and AMR: Integrating pathways, impacts, and artificial intelligence-driven mitigation.

The widespread contamination of the environment with antibiotic residues is a significant factor contributing to the global crisis of antimicrobial resistance (AMR). Antibiotics from various sources, such as effluents from municipal and hospital wastewater treatment plants, agricultural runoffs, discharges from pharmaceutical manufacturing and improper disposal of expired or unused medicines, create selective pressures in the spread of antibiotic resistance genes. These environmental reservoirs act as hotspots for horizontal gene transfer, facilitating the emergence of multidrug-resistant pathogens. Conventional detection methods including culture-based assays, chromatographic quantification, and molecular diagnostics, provide essential insights but are limited by low throughput, reduced sensitivity to new Antibiotic Resistance Genes, and challenges in real-time monitoring across complex environments. Recent advances, such as whole-genome sequencing, metagenomics, and biosensor-based detection, help to address these gaps by enabling more comprehensive surveillance of the resistome. Artificial intelligence further enhances these approaches by improving data interpretation and pattern recognition, thus complementing traditional and molecular methods rather than replacing them. This review examines the pathways of environmental antibiotic contamination, ecological and health impacts of AMR, and limitations of conventional detection methods. It aims to clarify how these pathways contribute to the AMR crisis, assess the effectiveness of existing surveillance techniques, and identify gaps in current research.

Anti-Bacterial Agents

AI-driven CRISPR screening: optimizing gene editing through automation and intelligent decision support.

BACKGROUND: CRISPR-based genetic screening has become a central methodology in functional genomics, enabling systematic interrogation of gene function, genetic interactions and context-dependent vulnerabilities at scale. However, the rapid expansion of screening modalities-including multi-condition designs, combinatorial perturbations, in vivo applications and single-cell readouts-has exposed fundamental limitations of heuristic-driven experimental design and post hoc statistical analysis. MAIN BODY: This Review synthesizes how artificial intelligence is reshaping CRISPR screening by introducing predictive, adaptive and system-level intelligence across the experimental lifecycle. We organize recent advances into two tightly coupled modules. First, machine learning and deep learning (ML/DL) methods optimize experimental design by learning context-dependent perturbation behavior, anticipating confounding effects and enabling iterative, information-efficient screening strategies. Second, large language model-agent (LLM-agent) systems complement these advances by externalizing scientific reasoning, integrating biological knowledge at scale and coordinating analysis and decision-making in human-in-the-loop workflows. CONCLUSIONS: Together, ML/DL and LLM-agent approaches reframe CRISPR screening from a static analytical pipeline into an intelligent experimental system, with important implications for robustness, scalability and biological discovery.

Artificial Intelligence

Beyond antibiotics: artificial intelligence-enabled anti-infective ecosystems for next-generation precision therapeutics against antimicrobial resistance.

The rapid global expansion of antimicrobial resistance (AMR) threatens to undermine decades of progress in infectious disease management and highlights the limitations of conventional antibiotic-centered therapeutic strategies. Although emerging technologies-including antimicrobial peptides, bacteriophage therapy, CRISPR-based antimicrobials, microbiome therapeutics, anti-virulence approaches, nanotechnology-enabled drug delivery, and artificial intelligence (AI)-have individually demonstrated considerable promise, they are predominantly being developed as independent interventions rather than as coordinated components of an integrated therapeutic strategy. This Perspective proposes the Intelligent Anti-Infective Ecosystem (IAIE) as a conceptual systems-level framework that computationally integrates multimodal diagnostics, pathogen genomics, microbiome profiling, AI-assisted decision support, programmable precision therapeutics, ecological monitoring, and longitudinal clinical feedback within a continuously learning dynamically optimized workflow. Unlike existing paradigms that primarily optimize individual technologies or therapeutic decisions, IAIE emphasizes closed-loop coordination among complementary antimicrobial approaches to support precision-guided infection management while preserving microbiome integrity and mitigating resistance selection pressure. We further outline the core components, operational principles, translational challenges, and technology readiness of the major therapeutic platforms that could contribute to such an ecosystem, while distinguishing clinically established interventions from emerging experimental strategies. Importantly, IAIE should be interpreted as a prospective conceptual architecture rather than an existing clinical platform. Its proposed clinical value remains to be established through sequential computational, preclinical, and prospective clinical investigations using standardized microbiological, ecological, and patient-centered outcome measures. By framing antimicrobial innovation within an responsive systems perspective, IAIE provides a roadmap for future multidisciplinary research aimed at integrating artificial intelligence and systems microbiology to enable sustainable management of antimicrobial resistance.

Humans

Artificial intelligence for anticancer drug discovery from natural products of macroalgae and sponges: A systematic review.

Marine natural products (MNPs) from macroalgae and marine sponges have inspired clinically important anticancer agents, including the cytarabine pharmacophore and the eribulin scaffold, while cyanobacterial dolastatin chemistry supplies the auristatin payloads of several marine-inspired antibody-drug conjugates (ADCs) such as brentuximab vedotin. Artificial intelligence (AI) methods, encompassing both classical machine learning (ML) with hand-engineered features and modern deep learning (DL) with many-layered neural networks, are increasingly supporting key decisions in natural-product anticancer drug discovery, including bioactivity prediction, target identification, absorption, distribution, metabolism, excretion and toxicity (ADMET) filtering, generative analogue design, and the selection of preclinical candidates. DL architectures relevant to this field include graph neural networks, transformer-based molecular generators, diffusion models for protein-ligand docking, and convolutional networks for mass spectrometry, while classical ML contributes interpretable fingerprint-based bioactivity models and molecular networking for dereplication. This review follows a systematic literature review methodology to organize the landscape of AI methods now applied to MNP anticancer discovery, distinguishing ML and DL approaches where relevant, situating them within the chemical context of macroalgal and sponge-derived oncology leads, and critically examining published case studies, including validation level (computational, in vitro, in vivo, clinical). The principal bottleneck for medical translation has shifted partly from algorithmic capability toward data infrastructure and experimental validation. Sparse, heterogeneous, and taxonomically biased bioactivity records limit what current models can learn and reduce the reliability of AI-prioritized candidates entering the preclinical pipeline. A roadmap is proposed that prioritizes open MNP-specific benchmarks, symbiont-aware modeling, and active learning loops with synthesizability and ADMET constraints. These AI workflows may accelerate the prioritization of marine-derived anticancer leads and support earlier, more evidence-based translational decisions in oncology drug development.

Biological Products

scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository.

Single-cell RNA sequencing has transformed cell biology by enabling precise transcriptomic measurements of individual cells. The Sequence Read Archive (SRA) is the largest public repository of sequencing reads, yet much of it remains underutilized due to unstandardized metadata. Here, we introduce scBaseCount, a database that leverages an AI agent to automate discovery and metadata extraction and standardize data processing. Built by mining all 10x Genomics datasets, scBaseCount is the largest public repository of single-cell gene expression data, comprising over 502 million cells across 27 organisms and 75 tissues. It offers an unbiased view of the data landscape within the SRA and enables the training of more performant computational models through access to broader phenotypic diversity. Uniform processing enables measurement of both intronic and exonic reads and non-coding gene expression and improves alignment across experiments. Moreover, scBaseCount provides a blueprint for how AI can be leveraged to autonomously curate biological data repositories.

Single-Cell Analysis

Vasoactive Agent Therapy in Septic Shock: From Monotherapy Battles to Tailored Hemodynamic Optimization.

Hemodynamic stabilization and preservation of organ perfusion are central elements in the management of septic shock. This is achieved by fluid resuscitation and by administration of vasoactive agents to secure a time window for definitive cause-directed therapy. Guided by the Surviving Sepsis Campaign, the optimization of vasoactive agent strategies, namely protective hemodynamic management, has become a central focus. Tracing key research over the past 25 years reveals a paradigm shift in vasopressor therapy, from empiricism to goal-directed strategy. This evolution has deepened our understanding of the benefit-risk profile of vasoactive agents and fostered a new conceptual framework regarding organ perfusion and protection. Under this framework, management strategies have advanced from the mere pursuit of hemodynamic parameters to care bundles that integrate the monitoring of organ perfusion, microcirculation, and oxygen metabolism. These advances have optimized agent selection, established safe dosing ranges, and ultimately promoted the widespread adoption of combined and multimodal therapy concepts. This review delineates this transformative journey, synthesizing evidence on the reappraisal of traditional agents and exploring "de-catecholaminization" strategies, thereby aiming to broaden the therapeutic landscape. The integration of artificial intelligence and genomic medicine is expected to further advance personalized management strategies for septic shock.

Humans

Integrating ex vivo platforms with AI to guide glioblastoma treatment.

PURPOSE: Ex vivo platforms can rapidly and cost-effectively screen patient-derived tumor cells or tissue. Artificial intelligence (AI) algorithms can search and identify patterns in large datasets and provide predictions. This review focuses on integrating microphysiological platforms with AI to inform physician and patient decision-making. METHODS AND RESULTS: Combining efficacy, safety, and pharmacology results from drug screens with the output of extensive AI searches can yield insights to guide physician and patient decision-making and potentially improve a patient's prognosis. We detail ex vivo platforms at different stages of development that represent the diversity of approaches: a microphysiological system and a high-throughput screen that assesses drug cytotoxicity in both bulk and drug-tolerant tumor cells. We review AI approaches that can enhance the utility of microphysiological platforms. CONCLUSION: Integrating emerging microphysiological platforms with AI is expected to significantly impact physician and patient choice of treatment.

Humans

A comprehensive review of AI innovations for tackling antimicrobial resistance.

Antimicrobial resistance (AMR) represents a major global public health concern, rendering available antimicrobials ineffective and leading to infections that are difficult to treat. Artificial intelligence (AI) has been increasingly applied across the AMR continuum, including resistance prediction, rapid diagnostics, new antimicrobial discovery, drug repurposing, antimicrobial surveillance, and clinical decision support. In this review, we aim to highlight recent developments in the use of artificial intelligence (AI) to address antimicrobial resistance (AMR). In addition, we review computational methods that help interpret genomic, phenomic, clinical, and epidemiological data to support the development of treatment strategies and novel antimicrobial agents. The key issues addressed include data quality, model interpretability, external validation, regulatory requirements, privacy, and fairness. While AI is not a complete solution to AMR, it can certainly strengthen the global AMR response by complementing key areas of AMR such as antimicrobial stewardship, infection prevention, laboratory diagnostics, and global surveillance.

Antimicrobial resistance (AMR)

Metabolic convergence of diabetes and prostate cancer: from dysglycemia to tumor microenvironment reprogramming.

The relationship between diabetes mellitus and prostate cancer (PC) represents one of the most intriguing paradoxes in cancer epidemiology, with diabetic individuals exhibiting a reduced incidence of PC yet poorer prognosis following diagnosis. This apparent contradiction underscores the need for an integrated understanding of how systemic metabolic dysfunction influences prostate carcinogenesis and disease progression. The present review critically synthesizes contemporary epidemiological, mechanistic, and translational evidence to establish metabolic convergence as a unifying framework linking diabetes-associated metabolic abnormalities with PC biology. Current evidence indicates that chronic dysglycemia, hyperinsulinemia, insulin resistance, and endocrine perturbations orchestrate interconnected intracellular signaling networks involving PI3K-AKT-mTOR, AMPK, AGE-RAGE signaling, oxidative stress, mitochondrial dysfunction, and epigenetic reprogramming, collectively driving metabolic adaptation and tumor evolution. Beyond tumor-intrinsic mechanisms, diabetes profoundly remodels the prostate tumor microenvironment through alterations in stromal metabolism, cancer-associated fibroblast activation, adipocyte-tumor crosstalk, extracellular matrix (ECM) remodeling, hypoxic adaptation, and vascular dysfunction, while simultaneously promoting immunometabolic reprogramming characterized by macrophage polarization, T-cell dysfunction, immune checkpoint activation, and immune evasion. The review further examines the bidirectional interactions between antidiabetic therapies and PC treatment, critically evaluating the translational potential of metformin and emerging glucose-lowering agents within the context of precision metabolic therapeutics. Finally, future directions encompassing biomarker-guided patient stratification, longitudinal metabolic profiling, multi-omics integration, artificial intelligence, and clinically relevant mechanistic validation are discussed as essential components of next-generation precision oncology. Collectively, this review reframes diabetes as an active metabolic determinant of PC rather than a coincidental comorbidity and highlights metabolism-centered precision strategies as promising avenues for improving risk stratification, therapeutic decision-making, and clinical outcomes in diabetes-associated PC.

Humans

What is on the Horizon Beyond Platinum and Immunotherapy for Patients With Advanced Non-Small Cell Lung Cancer Without Actionable Genomic Aberrations?

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. While targeted therapy and immunotherapy have transformed first-line management, most patients without actionable genomic alterations (AGAs) will experience disease progression within the first year of their initial treatment. Here, we review pivotal trials, emerging strategies, challenges, and unmet needs for patients with advanced NSCLC without AGAs. Docetaxel with or without ramucirumab is the standard second-line therapy for patients who have progressed after platinum-based chemotherapy and immunotherapy. Targeted therapy is only suitable for patients with specific AGAs. Understanding the hallmarks of cancer immune evasion is key to developing new strategies beyond chemoimmunotherapy. The combination of antiangiogenic agents with immune checkpoint inhibitors (ICIs) has shown mixed results after progression on platinum and ICI. Bispecific antibodies, particularly ivonescimab, have shown encouraging early efficacy in this space. Artificial intelligence-driven pathomics and radiomics tools may help to refine treatment selection in the future. Chimeric antigen receptor T-cell therapy remains investigational. Patients with advanced NSCLC without AGAs who progressed after chemoimmunotherapy have limited treatment options. Novel therapies such as specific antibodies have shown promising results. Future progress will depend on the development of predictive biomarkers and understanding the mechanisms of resistance to ICIs to guide drug development.

Humans

The application of AI-driven and engineered intratumoral microbes in cancer therapy.

BACKGROUND: Although investigations of the intratumoral microbiota date back thousands of years, breakthrough transformations have only recently been achieved through high-throughput sequencing and multiomic technologies. These advances have revealed diverse and tumor type-specific microbial communities that drive carcinogenesis via immunomodulation, metabolic reprogramming, and genomic instability. Current cornerstones of cancer therapies-including chemotherapy, radiotherapy, immunotherapy, and targeted therapy-are limited by systemic toxicity, localized tissue damage, drug resistance, and low patient response rates. These constraints underscore the urgent need for more effective and precise therapeutic strategies. MAIN BODY: This review comprehensively integrates artificial intelligence (AI) technologies into the characterization of the intratumoral microbiota, facilitating the development of novel computational pipelines for mapping microbe-host crosstalk. We systematically summarize recent advances in engineered microbial therapeutics, including bacteria designed for targeted antitumor activity and engineered microorganisms that enable the localized delivery of therapeutic agents. Furthermore, this review critically evaluates the safety profiles of microbiota-based interventions and discusses key challenges in clinical translation. CONCLUSIONS: By combining cutting-edge computational technologies, biological research, and clinical insights, this review aims to bridge the gap between microbiome science and oncological practice, pioneering innovative strategies for microbiota-guided diagnostics and personalized cancer therapy.

Humans

Nipah virus in the era of global connectivity: molecular evolution, transmission risk, and preparedness strategies.

Nipah virus (NiV) is a highly pathogenic zoonotic RNA virus belonging to the genus Henipavirus within the family Paramyxoviridae, representing a continuing global health concern due to its high case fatality rate and potential for epidemic expansion in the era of increasing international connectivity. The virus demonstrates strong evolutionary adaptability driven by the absence of proofreading mechanisms during RNA replication, enabling genetic diversification that may influence host range, virulence, and transmission dynamics. Molecular pathogenesis of NiV is primarily mediated through interaction of viral glycoproteins with ephrin-B2 and ephrin-B3 receptors, facilitating host cell entry, endothelial damage, and neuroinvasion. Immune evasion facilitated by the action of accessory proteins encoded by the P gene (P, V, W, and C) acts to suppress innate antiviral immunity through the inhibition of interferon induction and JAK/STAT signaling. Human-to-human transmission of Nipah virus remains limited, with epidemiological evidence indicating basic reproduction numbers generally below unity; however, respiratory involvement and healthcare-associated exposure may enhance cluster outbreaks. Global travel, ecological disruption, and fragmented surveillance systems contribute to spillover risk, particularly in South and Southeast Asia where fruit bats of the genus Pteropus serve as natural reservoirs. Despite advances in vaccine technology, including subunit, viral vector, mRNA-based platforms, and monoclonal antibody therapies, no licensed prophylactic or therapeutic agent is currently available for human use. Global preparedness remains challenged by the scarcity of high-containment biosafety facilities, limited research funding, and absence of integrated One Health surveillance networks. Ethical considerations surrounding wildlife population control further complicate disease mitigation strategies. Emerging genomic surveillance, artificial intelligence-assisted predictive modeling, and regional data-sharing frameworks are essential for early detection and response. Strengthening molecular research on viral-host interactions and transmission determinants will be critical for preventing future Nipah virus outbreaks in an increasingly interconnected world.

Genomic surveillance