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PathFound: An Agentic Multimodal Model Activating Evidence-seeking Pathological Diagnosis

arXiv:2512.23545v1 Announce Type: cross Abstract: Recent pathological foundation models have substantially advanced visual representation learning and multimodal interaction. However, most models still rely on a static inference paradigm in which whole-slide images are processed once to produce predictions, without reassessment or targeted evidence acquisition under ambiguous diagnoses. This contrasts with clinical diagnostic workflows that refine hypotheses through repeated slide observations and further examination requests. We propose PathFound, an agentic multimodal model designed to support evidence-seeking inference in pathological diagnosis. PathFound integrates the power of pathological visual foundation models, vision-language models, and reasoning models trained with reinforcement learning to perform proactive information acquisition and diagnosis refinement by progressing through the initial diagnosis, evidence-seeking, and final decision stages. Across several large multimodal models, adopting this strategy consistently improves diagnostic accuracy, indicating the effectiveness of evidence-seeking workflows in computational pathology. Among these models, PathFound achieves state-of-the-art diagnostic performance across diverse clinical scenarios and demonstrates strong potential to discover subtle details, such as nuclear features and local invasions.

Key Lipid Reprogramming Revealed in Gastric Signet Ring Cell Carcinoma by Spatial Mass Spectrometry Metabolomics

J Am Soc Mass Spectrom. 2025 Aug 6;36(8):1598-1608. doi: 10.1021/jasms.4c00505. Epub 2025 Jul 2.

ABSTRACT

Gastric signet ring cell carcinoma (GSRC) is an aggressive subtype of gastric cancer (GC) with a poor prognosis. The lack of a systematic molecular and metabolic heterogeneity overview has led to slow progress in clinical practice. This study used mass spectrometry imaging (MSI) to investigate the metabolic landscape of GSRC in GC tissue with various differentiation grades. Our comprehensive spatial profiling of metabolites and lipids unveiled distinct metabolic signatures across different tissue subregions. A substantial number of lipidomic biomarkers associated with GSRC were identified, including phosphatidylethanolamine N-methyl (PE-NMe), phosphatidylethanolamine (PE), sphingomyelin (SM), diacylglycerol (DG), phosphatidic acid (PA), and phosphatidylcholine (PC), which may provide insights into its pathogenesis and potential therapeutic targets. Furthermore, multi-omics network analysis revealed intricate metabolic pathways involved in GSRC progression. Our findings highlight the importance of understanding the metabolic heterogeneity of GSRC and pave the way for future studies exploring its clinical implications and therapeutic strategies.

PMID:40600435 | DOI:10.1021/jasms.4c00505

Minimal Residual Disease Detection: Implications for Clinical Diagnosis and Cancer Patient Treatment

MedComm (2020). 2025 May 15;6(6):e70193. doi: 10.1002/mco2.70193. eCollection 2025 Jun.

ABSTRACT

Minimal residual disease (MRD) serves as a pivotal biomarker for the clinical diagnosis and subsequent treatment of cancer patients. In hematological malignancies, MRD pose an increasingly serious threat to the health of Chinese people. Accurate MRD detection is essential for assessing relapse risk and optimizing therapeutic strategies, yet current methods such as flow cytometry, polymerase chain reaction (PCR), and next-generation sequencing (NGS) each have distinct limitations, and significant gaps remain in achieving optimal sensitivity and specificity of these technologies. This review provides a comprehensive analysis of MRD detection methods, high-lighting their clinical implications, including their roles in treatment decision-making, risk stratification, and patient outcomes. It discusses the strengths and weaknesses of existing techniques and explores emerging technologies that promise enhanced diagnostic precision. Key advancements such as integrating NGS with other methodologies and novel approaches like liquid biopsy and PCR are examined. The review underscores the academic and practical value of early and accurate MRD detection, emphasizing its impact on improving patient management and treatment outcomes. By addressing the limitations of current technologies and exploring future directions, this review aims to advance the field and support personalized medicine approaches to cancer treatment.

PMID:40384986 | PMC:PMC12079024 | DOI:10.1002/mco2.70193

PhenoMultiOmics: an enzymatic reaction inferred multi-omics network visualization web server

17 October 2024 at 18:00

Bioinformatics. 2024 Nov 1;40(11):btae623. doi: 10.1093/bioinformatics/btae623.

ABSTRACT

MOTIVATION: Enzymatic reaction play a pivotal role in regulating cellular processes with a high degree of specificity to biological functions. When enzymatic reactions are disrupted by gene, protein, or metabolite dysfunctions in diseases, it becomes crucial to visualize the resulting perturbed enzymatic reaction-induced multi-omics network. Multi-omics network visualization aids in gaining a comprehensive understanding of the functionality and regulatory mechanisms within biological systems.

RESULTS: In this study, we designed PhenoMultiOmics, an enzymatic reaction-based multi-omics web server designed to explore the scope of the multi-omics network across various cancer types. We first curated the PhenoMultiOmics database, which enables the retrieval of cancer-gene-protein-metabolite relationships based on the enzymatic reactions. We then developed the MultiOmics network visualization module to depict the interplay between genes, proteins, and metabolites in response to specific cancer-related enzymatic reactions. The biomarker discovery module facilitates functional analysis through differential omic feature expression and pathway enrichment analysis. PhenoMultiOmics has been applied to analyze the transcriptomics data of gastric cancer and the metabolomics data of lung cancer, providing mechanistic insights into interrupted enzymatic reactions and the associated multi-omics network.

AVAILABILITY AND IMPLEMENTATION: PhenoMultiOmics is freely accessed at https://phenomultiomics.shinyapps.io/cancer/ with a user-friendly and interactive web interface.

PMID:39418180 | PMC:PMC11549024 | DOI:10.1093/bioinformatics/btae623

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