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From Prediction to Foresight: The Role of AI in Designing Responsible Futures
Cognitive bias in LLM reasoning compromises interpretation of clinical oncology notes
How Do Companies Manage the Environmental Sustainability of AI? An Interview Study About Green AI Efforts and Regulations
Rigor in AI: Doing Rigorous AI Work Requires a Broader, Responsible AI-Informed Conception of Rigor
Smart spatial omics (S2-omics) optimizes region of interest selection to capture molecular heterogeneity in diverse tissues
Nat Cell Biol. 2025 Nov 26. doi: 10.1038/s41556-025-01811-w. Online ahead of print.
ABSTRACT
Spatial omics technologies have transformed biomedical research by enabling high-resolution molecular profiling while preserving the native tissue architecture. These advances provide unprecedented insights into tissue structure and function. However, the high cost and time-intensive nature of spatial omics experiments necessitate careful experimental design, particularly in selecting regions of interest (ROIs) from large tissue sections. Currently, ROI selection is performed manually, which introduces subjectivity, inconsistency and a lack of reproducibility. Previous studies have shown strong correlations between spatial molecular patterns and histological features, suggesting that readily available and cost-effective histology images can be leveraged to guide spatial omics experiments. Here we present Smart Spatial omics (S2-omics), an end-to-end workflow that automatically selects ROIs from histology images with the goal of maximizing molecular information content in the ROIs. Through comprehensive evaluations across multiple spatial omics platforms and tissue types, we demonstrate that S2-omics enables systematic and reproducible ROI selection and enhances the robustness and impact of downstream biological discovery.
PMID:41298871 | DOI:10.1038/s41556-025-01811-w
Information content as a health system screening tool for rare diseases
npj Digital Medicine, Published online: 25 November 2025; doi:10.1038/s41746-025-02096-x
Information content as a health system screening tool for rare diseasesHuman Experts' Evaluation of Generative AI for Contextualizing STEAM Education in the Global South
Rewiring the transcriptome: diagnostic and therapeutic implications of alternative splicing in solid cancers
Mol Biol Rep. 2025 Nov 26;53(1):125. doi: 10.1007/s11033-025-11302-8.
ABSTRACT
Alternative splicing (AS) is a fundamental mechanism of pre-mRNA processing that allows one gene to create numerous transcript and protein isoforms, thereby substantially increasing the diversity of the human proteome. AS occurs co-transcriptionally (when the nascent pre-mRNA is still being generated from chromatin) or post-transcriptionally after the release of the transcript, and both modalities contribute to the control of isoform expression in a tissue- and context-dependent manner. Under normal physiological conditions, AS is tightly regulated in a tissue- and context-dependent manner. However, in malignancies, this regulatory precision is often lost, leading to extensive splicing aberrations that promote oncogenic transformation, tumor progression, and resistance to therapy. Solid tumors, in particular, exhibit a high frequency of aberrant splicing events, which frequently give rise to oncogenic isoforms or the suppression of tumor-inhibitory variants. These disruptions contribute to key cancer hallmarks such as uncontrolled proliferation, resistance to apoptosis, neoangiogenesis, and epithelial-mesenchymal transition (EMT). Recent findings underscore the clinical relevance of splicing-derived molecular signatures. Distinct splicing profiles have been correlated with diagnostic, prognostic, and predictive outcomes in multiple solid tumors-including breast, prostate, lung, colorectal, and central nervous system malignancies. Notably, tumor-specific alternative splice variants often generate unique exon-exon junctions (neojunctions) that encode immunogenic peptides, representing a promising class of neoantigens for immunotherapy. These neoantigens are fueling the development of personalized treatment modalities such as splicing-directed vaccines and T cell-based therapies. The advent of advanced technologies-including long-read sequencing, single-cell transcriptomics, and proteogenomics-has enabled high-resolution mapping of cancer-specific splice variants and enhanced our understanding of their functional relevance. Therapeutic strategies targeting aberrant splicing are also advancing, with splice-switching oligonucleotides, small-molecule modulators, and CRISPR-based RNA-editing platforms emerging as innovative approaches. Despite these advances, challenges such as splicing heterogeneity, off-target effects, and incomplete protein-level validation continue to hinder clinical translation. This review offers an integrated overview of the molecular drivers and clinical implications of alternative splicing in cancer. It emphasizes the potential of AS-based diagnostics and therapeutics within precision oncology and highlights the importance of multi-omic integration and clinical validation to fully harness the therapeutic opportunities of splicing dysregulation.
PMID:41296088 | DOI:10.1007/s11033-025-11302-8
Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas: current understanding and perspectives on malignant progression
J Gastroenterol. 2025 Nov 26. doi: 10.1007/s00535-025-02328-7. Online ahead of print.
ABSTRACT
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are bona fide cystic precursor lesions to pancreatic ductal adenocarcinoma (PDAC), which is the cancer type with the most dismal prognosis. Since IPMNs are detectable by imaging, they offer a rare window of opportunity for early intervention for PDAC development. Despite their clinical visibility, the molecular pathogenesis of IPMNs remained incompletely understood, and no effective non-surgical therapeutic strategies have been established to date. In the past few decades, however, substantial progress has been made in elucidating their molecular pathology. Next-generation sequencing technologies demonstrated the comprehensive genetic mutation profile of IPMNs in the early 2010s. Elucidation of these mutation profiles enabled the establishment of genetically engineered mouse models, successfully recapitulating the natural development of human IPMNs and their progression to invasive cancer. Rapid evolution of "omics" technologies in recent years has facilitated the application of mass spectrometry, single-cell sequencing and spatial transcriptomics to IPMNs, significantly advancing our understanding of their pathophysiology. These techniques elucidated the changes in transcriptome, proteome, metabolome, microbiome, and tumor microenvironment associated with IPMN development and progression. This review summarizes current insights into the molecular and cellular landscapes of IPMN tumorigenesis, with particular emphasis on the mechanisms driving malignant progression.
PMID:41296011 | DOI:10.1007/s00535-025-02328-7