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Big data analytics for CLEC5A dynamics based on single cell genomics and proteomics reveal its diverse functions in human diseases.

BACKGROUND: CLEC5A (C-type lectin domain family 5 member A) is an innate immune receptor implicated in inflammatory signaling, contributing to hyperinflammatory responses in infections and sterile inflammation. However, CLEC5A dynamics in human diseases remain to be identified. Here, we systematically characterized CLEC5A dynamics in humans across cells, tissues, and disease states, and to explore the functional significance of CLEC5A in macrophage activation based on single-cell genomics. METHODS: With multi-omics (scRNA-seq, proteomics and big data analytics), we analyzed extensive human transcriptomic datasets (>42,000 samples) to profile CLEC5A expression by cell type, tissue, and disease. Single-nucleus RNA-seq (snRNA-seq) from pediatric congenital heart disease and a virtual CLEC5A gene knockout were also performed to characterize CLEC5A dynamics in humans. RESULTS: CLEC5A is highly enriched in innate immune cells, particularly in macrophages and neutrophils. Baseline CLEC5A in most tissues is low, but it is markedly upregulated in inflammatory and infectious diseases. CLEC5A expression has sex-specific differences in certain organs. Single-cell analysis showed that CLEC5A can be considered novel marker of proinflammatory macrophages with elevated cytokine production, antigen presentation, and impaired phagocytosis. Virtual CLEC5A knockout analysis identified coordinated perturbation of immune-regulatory pathways and overlapping genes linking CLEC5A to macrophage activation networks. CONCLUSION: CLEC5A is predominantly expressed in myeloid cells and acts as a key amplifier of inflammation in human diseases. Our findings highlight CLEC5A as a potential biomarker and therapeutic target in myeloid-driven hyperinflammatory conditions, warranting further experimental and translational validation.

Humans

Advances in tumor subclone formation and mechanisms of growth and invasion.

Tumor subclones refer to distinct cell populations within the same tumor that possess different genetic characteristics. They play a crucial role in understanding tumor heterogeneity, evolution, and therapeutic resistance. The formation of tumor subclones is driven by several key mechanisms, including the inherent genetic instability of tumor cells, which facilitates the accumulation of novel mutations; selective pressures from the tumor microenvironment and therapeutic interventions, which promote the expansion of certain subclones; and epigenetic modifications, such as DNA methylation and histone modifications, which alter gene expression patterns. Major methodologies for studying tumor subclones include single-cell sequencing, liquid biopsy, and spatial transcriptomics, which provide insights into clonal architecture and dynamic evolution. Beyond their direct involvement in tumor growth and invasion, subclones significantly contribute to tumor heterogeneity, immune evasion, and treatment resistance. Thus, an in-depth investigation of tumor subclones not only aids in guiding personalized precision therapy, overcoming drug resistance, and identifying novel therapeutic targets, but also enhances our ability to predict recurrence and metastasis risks while elucidating the mechanisms underlying tumor heterogeneity. The integration of artificial intelligence, big data analytics, and multi-omics technologies is expected to further advance research in tumor subclones, paving the way for novel strategies in cancer diagnosis and treatment. This review aims to provide a comprehensive overview of tumor subclone formation mechanisms, evolutionary models, analytical methods, and clinical implications, offering insights into precision oncology and future translational research.

Humans

The Computational Revolution in Natural Product Research: A Data-Driven Roadmap for Next-Generation Drug Development.

Natural products (NPs) have historically provided the foundational scaffolds for drug development, yet traditional bioprospecting faces critical limitations: high rediscovery rates, laborious isolation workflows, and substantial attrition during clinical translation. The emergence of big data technologies is fundamentally transforming this landscape, enabling a shift from serendipity-based discovery toward systematic, data-driven approaches. This review examines how the integration of artificial intelligence (AI), machine learning (ML), and multi-omics datasets is accelerating natural product research across three key domains: (1) genome mining for biosynthetic gene cluster identification using platforms such as antiSMASH, (2) cheminformatics-driven prediction of structure-activity relationships and ADMET properties, and (3) metabolomics-guided dereplication to prioritize novel bioactive scaffolds. We evaluate the convergence of genomics, metabolomics, and computational chemistry in enabling in silico lead optimization and the discovery of cryptic metabolites from previously inaccessible microbial taxa. While challenges in data standardization and scalability persist, the synergy between big data and NP research is accelerating clinical translation. Despite persistent challenges in data standardization, scalability, and equitable benefit-sharing, the convergence of big data and NP research is poised to redefine drug development. These advances position computational NP research as a cornerstone of next-generation drug development.

big data analytics

Big data in multiple sclerosis.

PURPOSE OF REVIEW: This review summarizes recent key advancements in multiple sclerosis (MS) achieved through the utilization of big data from diverse sources and advanced analytical techniques. RECENT FINDINGS: Real-world evidence (RWE) derived from MS big data has significantly enhanced treatment strategies, redefined the concept of disease progression, refined prognostic models, and facilitated personalized medicine. RWE has highlighted the long-term benefits of early intensive treatment compared to escalation strategies, the unfavorable risk profile associated with treatment de-escalation and the importance of managing treatments during pregnancy. Additionally, it has revealed similarities and differences in the effectiveness and safety of specific high-efficacy therapies, as well as key predictors for switching treatments. RWE has also emphasized the central role of progression independent of relapse activity as a significant driver of disability and predictor of unfavorable long-term outcomes in both adult and pediatric onset MS. A data-driven approach utilizing artificial intelligence and big data has established a comprehensive framework for understanding the disease's evolution. Multimodal big data frameworks - encompassing clinical data, MRI, genomics, biomarkers, and app-based metrics - have demonstrated their ability to enhance diagnostic performance and risk stratification in MS. SUMMARY: Big data approaches are transforming MS research and clinical practice by providing stronger RWE to guide therapeutic decision-making, refining models of disease progression, and developing more precise prognostic tools.

Humans

Proteomics at scale: Bottlenecks and opportunities for early-career researchers in a fast developing field.

The field of proteomics has rapidly evolved over the last five years enabled by rapid advances in instrumentation and computation. At the same time, the proteomics community is also growing. This is reflected by the increasing participation in international conferences such as those organized by the European Proteomics Association and the Human Proteome Organization. These events provide early-career researchers with unique opportunities to exchange ideas, develop collaborations, and build networks that support professional development. One such network is the Young Proteomics Investigators Club, a European initiative supported by European Proteomics Association and led by early-career researchers. In this Community-Driven project, we investigate recent trends in proteomics by screening conference abstracts and evaluating the session attendance at Human Proteome Organization Congresses and European Proteomics Association conferences. Based on these analyses, we identified five areas that, from our perspective, are shaping the current trends in proteomics: clinical proteomics, proteomics of post-translational modifications, single-cell proteomics, systems biology and multi-omics, and computational proteomics. For each area, we highlight both unique challenges and identify a common theme: a shift from exploratory studies with manageable sample numbers towards large screenings and cohorts and the generation of big data, which often comes with the lack of computational support, organizational networks, and infrastructure. In this light, we describe the unique challenges and opportunities faced by early-career researchers. We point to actionable directions for enabling reproducible and transparent proteomics as well as community-driven projects and initiatives, which are often providing training and support. SIGNIFICANCE: In this perspective, the Young Proteomics Investigators Club (YPIC) discusses advances in analytical developments and computational approaches in proteomics research. Based on empirical analysis of recent European Proteomics Association conference and Human Proteome Organization congresses contributions, we identify clinical, single-cell, post-translational and systems-level proteomics as the research areas that have gained most momentum in the last three to five years. What makes this work distinctive is that it is written by and for early-career researchers, thereby uniquely identifying where momentum, challenges, and unmet needs converge for the newest generation of proteomics researchers. Rather than cataloguing advances, we examine the widening gap between what modern proteomics can generate and what individual researchers can realistically process, validate, and interpret. We describe specific structural barriers including access to high performance computing, limited formal training in scalable data analysis, the need for unified benchmarking standards and navigating clinical collaboration frameworks. We then highlight opportunities for the field, such as community-curated benchmarks, interdisciplinary mentorship models, and shared computational infrastructure. By making these challenges explicit from an early-career researchers standpoint, we aim to inform how training, funding, and community initiatives can be shaped to support the next generation of proteomics researchers.

Proteomics