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At least 253 records · Page 14Linked to original sources

Induced pluripotent stem cell reprogramming: methodological evolution and challenges in clinical translation.

Cell reprogramming can transform somatic cells into induced pluripotent stem cells providing a platform for patient-specific disease modeling, drug screening and regenerative medicine research. Since the advent of OKSM-mediated reprogramming, the system of technical approaches has evolved continuously - from integrated viral vectors to non-integrated episomal systems and, more recently, chemical reprogramming and CRISPR approaches. The simultaneous advances in single-cell multi-omics, biomaterials engineering, and artificial intelligence have further refined the controllability and precision of the reprogramming process. Despite these innovations, problems persist that hinder clinical translation: incomplete epigenetic resetting, ongoing clonal heterogeneity, genomic instability in long-term culture, and the lack of standardized Good Manufacturing Practice protocols for large-scale manufacturing. This review summarizes the trajectory of iPSC reprogramming technologies, with special emphasis on the translational applicability of each modality. We evaluated viral and nonviral delivery systems, chemical reprogramming, strategies that aid gene editing, and emerging engineering platforms, including microfluidics, smart biomaterials, and artificial-intelligence-driven process optimization. We further identify the core "translational triltrilas", namely, the inherent tradeoffs between security, homogeneity, and scalability, and propose a comprehensive strategy to overcome these bottlenecks. By linking basic mechanistic understandings with industrial and regulatory considerations, this review aims to provide a route for transitioning iPSC technology from a laboratory tool to a clinically viable manufacturing platform.

clinical translation↗

Label-free detection methods for protein microarrays.

With the growth of the "-omics" such as functional genomics and proteomics, one of the foremost challenges in biotechnologies has become the development of novel methods to monitor biological process and acquire the information of biomolecular interactions in a systematic manner. To fully understand the roles of newly discovered genes or proteins, it is necessary to elucidate the functions of these molecules in their interaction network. Microarray technology is becoming the method of choice for such a task. Although protein microarray can provide a high throughput analytical platform for protein profiling and protein-protein interaction, most of the current reports are limited to labeled detection using fluorescence or radioisotope techniques. These limitations deflate the potential of the method and prevent the technology from being adapted in a broader range of proteomics applications. In recent years, label-free analytical approaches have gone through intensified development and have been coupled successfully with protein microarray. In many examples of label-free study, the microarray has not only offered the high throughput detection in real time, but also provided kinetics information as well as in situ identification. This article reviews the most significant label-free detection methods for microarray technology, including surface plasmon resonance imaging, atomic force microscope, electrochemical impedance spectroscopy and MS and their applications in proteomics research.

Animals↗

RePo index: a multidimensional framework to quantify genetic resilience in data-limited amphibian faunas.

This study explores the resilience of Chilean amphibians to environmental disturbances through an integrative approach that combines ecological, demographic, bibliometric, and molecular information. A total of 58 species distributed across 14 genera and 9 families were evaluated via the resilience potential (RePo) index, which incorporates eleven criteria grouped into five dimensions: distribution, population trends, emerging diseases, evolutionary history, and genetic records. The results revealed high ecological vulnerability: 83% of the species were classified as non resilient (45% with no resilience and 38% with low resilience), and none reached the high-resilience category. At the family level, Telmatobiidae presented the lowest resilience values, whereas Leptodactylidae presented the highest. At the genus level, Insuetophrynus was identified as the most vulnerable taxon, with no molecular records and an extremely restricted distribution. In contrast, species such as Rhinella spinulosa and Pleurodema thaul presented moderate resilience, suggesting greater adaptive potential and relevance for functional studies. From a bibliometric perspective, a bias toward classical research topics (distribution, physiology, and taxonomy) was detected, with limited representation of integrative approaches such as genetic conservation or climate change. The conceptual modularity in the literature was low (Q = 0.1328), indicating weak thematic differentiation and little integration of omics tools. Most species lack transcriptomic and genomic data, severely limiting the assessment of their adaptive mechanisms. In this context, the RePo index has emerged as an integrative tool useful for operationalizing concepts such as evolutionarily significant units (ESUs) and management units (MUs), which are essential for evidence-based conservation. Finally, this study highlights the need to incorporate high-throughput sequencing (HTS) technologies and to participate in international initiatives, such as the Amphibian Genomics Consortium, as a strategic path forward for advancing adaptive conservation of Chilean amphibians.

Animals↗

Towards discovery-driven translational research in breast cancer.

Discovery-driven translational research in breast cancer is moving steadily from the study of cell lines to the analysis of clinically relevant samples that, together with the ever increasing number of novel and powerful technologies available within genomics, proteomics and functional genomics, promise to have a major impact on the way breast cancer will be diagnosed, treated and monitored in the future. Here we present a brief report on long-term ongoing strategies at the Danish Centre for Translational Breast Cancer Research to search for markers for early detection and targets for therapeutic intervention, to identify signalling pathways affected in individual tumours, as well as to integrate multiplatform 'omic' data sets collected from tissue samples obtained from individual patients. The ultimate goal of this initiative is to coalesce knowledge-based complementary procedures into a systems biology approach to fight breast cancer.

Biomarkers, Tumor↗

Advances in plant proteomics.

With the avalanche of genomic information and improvements in analytical technology, proteomics is becoming increasingly important for the study of many different aspects of plant functions. Since proteins serve as important components of major signaling and biochemical pathways, studies at protein levels are essential to reveal molecular mechanisms underlying plant growth, development, and interactions with the environment. The plant proteome is highly complex and dynamic. Although great strides need to be taken towards the ultimate goal of characterizing all the proteins in a proteome, current technologies have provided immense opportunities for high-throughput proteomic studies that have gone beyond simple protein identification to analyzing various functional aspects, such as quantification, PTM, subcellular localization, and protein-protein interactions. In this review of plant proteomics, advances in protein fractionation, separation, and MS will be outlined. Focus will be on recent development in functional analysis of plant proteins, which paves the way towards the comprehensive integration with transcriptomics, metabolomics, and other large scale "-omics" into systems biology.

Algorithms↗

Microbial diversity: the essential foundation for life on our planet.

The biological basis of life on Earth is microbial diversity that ensures human health, agricultural productivity, ecological balance, and ecosystem functioning. Microorganisms enable ecosystem restoration through bioremediation, maintain soil fertility, support plant growth, manage vital biogeochemical cycles, and contribute to climate resilience. Precision probiotics, postbiotics, faecal microbiota transplantation, and personalized microbiome medicine are the examples of emerging microbiome-based therapies that offer promising therapeutic opportunities. In humans, the gut microbial community is essential for immune regulation, metabolism, and disease prevention. In terrestrial ecological systems, interactions between plants, fungi, bacteria, and other soil microorganisms improve carbon sequestration, nutrient cycling, stress resilience, and sustainable agricultural productivity in the given effects of climate change. Emerging uses in agriculture, environmental restoration, and medicine are made possible by advancements in multi-omic techniques, synthetic microbial genomes, microbiome engineering, and artificial intelligence. Considering these developments, issues with ecological complexity, long-term validation, standardization, and field scale application still exist. Therefore, preserving microbial diversity is important for conserving ecological resilience and strengthening the One Health framework, which highlights the mutual dependance of health of animal, human, plant, and environment. This review summarizes what has been discovered about ecological and biomedical relevance of microbiome, identifies important research gaps, highlighting emerging technologies, and evaluates potential future directions for using microbiome to support planetary sustainability.

Bioremediation↗

Proteomics-based approaches to neutrophil biology.

INTRODUCTION: Neutrophils are central effectors of innate immunity and key contributors to inflammation, host defense, and tissue injury across a wide range of physiological and pathological contexts. Due to their short lifespan, rapid activation, and extensive post-translational regulation, comprehensive molecular characterization of neutrophil function requires approaches that go beyond transcriptomics or marker-based analyses. AREAS COVERED: This review summarizes how proteomic technologies have advanced the understanding of neutrophil biology by enabling unbiased, system-wide profiling of protein abundance, subcellular organization, post-translational modifications, and functional heterogeneity. We discuss global and subcellular proteomics, PTM-centric analyses, and emerging low-input and single-cell proteomic strategies, highlighting recent studies of infection, cancer, metabolic disorders, aging, autoimmune disease, and inflammation. The literature covered includes current large-scale quantitative proteomics, targeted PTMs, and integrative multi-omics studies in both human samples and relevant experimental models. EXPERT OPINION: Proteomics has established neutrophils as highly plastic and context-dependent cells whose functions are governed by coordinated remodeling of signaling, metabolism, and effector pathways. Future progress will depend on expanding neutrophil-specific PTM maps, improving low-input workflows, and integrating single-cell and spatial proteomics. Together, these advances are expected to redefine neutrophil functional states and accelerate translation toward clinically meaningful biomarkers and therapeutic strategies.

Humans↗

Integrative Multi-Omics Deciphering of Gu Shu Kang Granules: A Comprehensive Systems Biology Approach to Unraveling Molecular Mechanisms in Sarcopenia-Osteoporosis Intervention.

INTRODUCTION: Sarcopenia is a degenerative musculoskeletal disease affecting the elderly, significantly impairing patients' quality of life and challenging modern medicine. This study innovatively combines Traditional Chinese Medicine (TCM) theories with modern medical research to explore the mechanisms by which Gushukang granules address sarcopenia. METHODS: The research integrated multi-dimensional research methods, including network pharmacology, metabolomics, and animal experiments, to comprehensively investigate the scientific mechanisms of Gushukang granules' intervention in sarcopenia. RESULTS: Network pharmacology analysis identified multiple potential targets related to muscle growth and repair. UPLC-Q-TOF MS technology tracked metabolic pathways, while animal experiments verified that Gushukang granules precisely regulate muscle metabolic balance by modulating key signaling pathways involved in protein synthesis and degradation. DISCUSSION: The findings demonstrate the potential of integrating traditional and modern medical approaches in addressing age-related muscle degradation, providing scientific validation for TCM treatment of sarcopenia. CONCLUSION: This study establishes a model for modernizing TCM research, offering solid scientific evidence for comprehensive intervention of chronic diseases in the elderly and highlighting the TCM concept of "preventing disease before its onset" in modern medical translation.

Sarcopenia↗

'Omic' and hypothesis-driven research in the molecular pharmacology of cancer.

Given the layered, evolutionary complexity of biological systems, it will not be possible to understand them comprehensively on the basis of hypothesis-driven research alone. Likewise, it will not be possible to do so solely through 'omic' studies of genes, proteins and other molecules in aggregate. The two modes of research are complementary and synergistic. The twin complexities of cancer biology and drug discovery demand such synergy as a basis for the next generation of oncopharmacomic research.

Animals↗

Toxicologic pathology: looking ahead.

The field of toxicologic pathology is being impacted, as are other fields of science and medicine, by rapid transitions to take advantage of new science and technology. The new technology represents great opportunities to advance our understanding of toxicology and pathology to exciting new levels, but it also poses new challenges. We must be seriously engaged in that transition to assure that the outcome reflects the knowledge and discipline that are hallmarks of today's decision-making process in areas of product development and approval. New expertise will be required to deal with new issues. How well and how rapidly we adapt as the field moves from "...icities" to "...omics" will, at least in part, determine the role of toxicologic pathologists in the product development and approval processes of the future.

Animals↗

Unlocking the Circulating Proteome: Toward Clinical Translation.

Blood-based proteomics is approaching a translational inflection point. Driven by advances in measurement technologies, rapid expansion of analytical capabilities, and growing adoption across research and medical communities, there is increasing demand for clinically actionable biomarkers. As the field transitions away from purely large-scale discovery-oriented studies toward more informed, targeted, application-driven analyses, the generation of proteomic data is no longer the bottleneck. Instead, the central challenge is to translate these measurements into robust, reproducible, and clinically meaningful insights. In this Review, we assess recent technological and methodological developments, evaluate persistent preanalytical and interpretative limitations, and outline the key steps required for clinical translation. We focus on three deeply interconnected dimensions: the capabilities and constraints of current measurement platforms, the role of computational and machine learning approaches in extracting biological and clinical signals, and the emergence of large-scale population studies that create new opportunities for validation and generalization. Finally, we discuss a forward-looking vision in which proteomics plays a central role in dynamic, multilayered omics frameworks, where integration with genomics, temporal profiling, and imaging can deepen our understanding of health, disease, and therapeutic response.

Humans↗

Cytomics: A multiparametric, dynamic approach to cell research.

Cytomics aims to determine the molecular phenotype of single cells. Within the context of the -omics, cytomics allows the investigation of multiple biochemical features of the heterogeneous cellular systems known as the cytomes. Cytomics can be considered as the science of single cell-based analyses that links genomics and proteomics with the dynamics of cell and tissue function, as modulated by external influences. Inherent to cytomics are the use of sensitive, scarcely invasive, fluorescence-based multiparametric methods and the event-integrating concept of individual cells to understand the complexity and behaviour of tissues and organisms. Among cytomic technologies, flow cytometry, confocal laser scanning microscopy and laser capture microdissection are of great relevance. Other recent technologies based on single cell bioimaging and bioinformatic tools become important in drug discovery and toxicity testing, because of both high-content and high-troughput. The multiparametric capacity of cytomics is very useful for the identification, characterization and isolation of stem cell populations. In our experience, flow cytometry is a powerful and versatile tool that allows quantitative analysis of single molecules, prokaryotic and eukaryotic cells for basic, biotechnological, environmental and clinical studies. The dynamic nature of cytomic assays leads to a real-time kinetic approach based on sequential examination of different single cells from a population undergoing a dynamic process, the in fluxo level. Finally, cytomic technologies may provide in vitro methods alternative to laboratory animals for toxicity assessment.

Animals↗

Genome-based exploration of volatile flavor diversity from food yeast species.

Yeast shares a longer than 10 000-year history with humans in food fermentation by producing various volatile flavor compounds that contribute to the final taste and aroma of foods. Yeast-associated volatile flavor compounds include esters, benzenoids, sulfur compounds, and phenolic derivatives, which enhance the sensory complexity of fermented foods and beverages. Genome-scale technologies have advanced and transformed our understanding of the genetic and evolutionary drivers of volatile flavor diversity. The conventional approach to aroma enrichment and flavor balancing through single-strain optimization has been redefined through yeast cofermentation strategies, such as the pairing of Saccharomyces cerevisiae with nonconventional yeast species. This minireview summarizes the latest genomic insights into volatile flavor compound formation through ester, benzenoid, sulfur, and phenolic pathways in various yeast species and highlights the shaping of the next generation of food fermentation innovation via cofermentation combined with omics analysis, followed by a future perspective on synthetic biology for industrial applicability.

Volatile Organic Compounds↗

A scalable HPC framework for bioinformatics in resource-limited settings: design principles, implementation, and sustainability from the UVRI experience.

MOTIVATION: Building and sustaining High-Performance Computing (HPC) infrastructure for bioinformatics research in resource-limited settings presents significant technical, financial and operational challenges. Institutions in low-and middle-income regions often face constraints such as limited technical expertise, unstable infrastructure and restricted funding which can hinder the deployment of large-scale computational platforms necessary for modern genomics and bioinformatics analyses. RESULTS: We present a scalable and modular HPC framework developed at the Uganda Virus Research Institute (UVRI) to support large-scale genomics and other omics data analyses in resource-limited settings. The framework integrates open-source HPC management tools, infrastructure automation, and reproducible configuration management to enable reliable deployment and maintenance. Optimized storage and networking configurations combined with a phased capacity-building strategy support high-throughput genomic workflows while strengthening local technical expertise. From our implementation experience, we derive ten practical design and operational rules that provide a transferable methodology for establishing and sustaining in-house HPC infrastructure. These rules emphasize strategic investment in human capacity, structured planning, leveraging collaborations, adoption of open-source technologies and service management practices to improve operational resilience and long-term sustainability. AVAILABILITY: The design principles, automation strategies and implementation guidelines described in this work are applicable to institutions seeking to establish sustainable HPC resources for bioinformatics research in resource-constrained environments.

Computational Biology↗

Bioinformatic approach for understanding the heterogeneity of cholangiocytes.

It is remarkable that microarray technologies have nearly reached a pinnacle. Establishment of further analysis and management of enormous data derived from microarray technology is currently the highest priority. The heterogeneous functions of cholangiocytes regulate the pathophysiology of the biliary epithelium in relation to secretory, proliferative and apoptotic activities. Distinct expression profiles of two murine cholangiocyte lines, termed small and large have been revealed by microarray analysis. The features of the two cholangiocyte cell lines, categorized partly according to gene ontology, indicate the specific physiological role of each cell line. The large cholangiocytes are characterized as "transport" and "immune/ inflammatory responses". In contrast, small cholangiocytes are associated with properties of limited physiological functional ability and proliferating/migrating potential with specific molecules like Eph receptors, comparable to mesenchymal cells. 'Omic study will be of great help in understanding the heterogeniety of cholangiocytes.

Animals↗

Promises and pitfalls of long-read sequencing for resolving microbial complexity.

Long-read sequencing (LRS) has driven a transition in microbial genomics, overcoming the assembly fragmentation inherent to short-read sequencing. This review elucidates the impact of LRS across isolate genomics, metagenomics, and multi-omics domains. By spanning extensive repetitive regions, LRS facilitates the reconstruction of circular chromosomes and precisely resolves mobile genetic elements (MGEs). In metagenomics, LRS enables strain-level resolution, the recovery of circular metagenome-assembled genomes, and the precise localization of MGEs within host replicons. Furthermore, the single-molecule, amplification-free properties of LRS provide enhanced resolution of native epigenetic modifications and full-length transcriptomes. Despite these advancements, widespread implementation remains constrained by multidimensional challenges, including stringent high-molecular-weight DNA requirements, depth deficits, and computational overhead. Nevertheless, LRS is increasingly becoming the method of choice for isolate genomics and metagenomics. As detection technologies and algorithms progress, LRS will further improve our ability to decipher the structural and functional diversity of microbial ecosystems.

Metagenomics↗

Rethinking GWAS: how lessons from genetic screens and artificial intelligence could reveal biological mechanisms.

MOTIVATION: Modern single-cell omics data are key to unraveling the complex mechanisms underlying risk for complex diseases revealed by genome-wide association studies (GWAS). Phenotypic screens in model organisms have several important parallels to GWAS which the author explores in this essay. RESULTS: The author provides the historical context of such screens, comparing and contrasting similarities to association studies, and how these screens in model organisms can teach us what to look for. Then the author considers how the results of GWAS might be exhaustively interrogated to interpret the biological mechanisms underpinning disease processes. Finally, the author proposes a general framework for tackling this problem computationally, and explore the data, mechanisms, and technology (both existing and yet to be invented) that are necessary to complete the task. AVAILABILITY AND IMPLEMENTATION: There are no data or code associated with this article.

Genome-Wide Association Study↗

A Multi-omics Exploration Revealing SLIT2 as a Prime Therapeutic Target for Peripheral Facial Paralysis: Integrating Single-Cell Transcriptomics and Plasma Proteome Data.

Peripheral facial paralysis (PFP) is a common neurological disorder characterized by facial-nerve dysfunction. Identifying therapeutic targets and understanding the molecular and cellular mechanisms underlying PFP are crucial for developing effective treatment strategies. This study combined Mendelian randomization (MR) analysis and single-cell RNA sequencing (scRNA-seq) to explore potential therapeutic candidates and their roles in PFP pathophysiology. The MR analysis included 1925 publicly available plasma protein cis-heritability instruments. Instrumental variables were selected for MR analysis to identify plasma proteins associated with PFP, followed by colocalization analysis to evaluate shared genetic variants between the identified proteins and PFP. After the initial identification of plasma proteins associated with Bell's palsy using MR analysis, a rat model of facial-nerve injury was established to further dissect underlying mechanisms at cellular and molecular levels. Using scRNA-seq technology, we delved deeply into cellular Heterogeneity and dynamic changes in gene expression in the facial-nerve nucleus tissues under both injured and control conditions, thereby achieving a systematic study ranging from macroscopic genetic associations to microscopic cellular functions. Finally, expression patterns were preliminarily validated by performing in vitro immunofluorescence analysis on the facial-nerve nucleus samples of SD rats. The MR analysis results identified 30 plasma proteins significantly associated with PFP, with nine target genes showing differential expression in the scRNA-seq data. Colocalization analysis demonstrated that slit guidance Ligand 2 (SLIT2), semaphorin 4D (SEMA4D), EGF containing fibulin extracellular matrix protein 1 (EFEMP1), and sprouty related EVH1 domain containing 2 (SPRED2) shared causal variants with PFP. SLIT2 was highly expressed in the microglia and inhibitory neurons in the experimental group, whereas SEMA4D showed elevated expression across multiple glial cell types in the same group. In contrast, EFEMP1 and SPRED2 showed distinct expression patterns in fibroblasts and oligodendrocytes. The role of SLIT2 has been previously well-documented in many central nervous system diseases. However, for the first time, this study detected SLIT2 alteration after facial-nerve injury. Altered intercellular signaling, particularly enhanced SLIT2-ROBO signaling between neurons and glial cells, was observed in the PFP group. Pseudotime analysis revealed dynamic SLIT2 expression during microglia and inhibitory neuron differentiation, mirroring changes in ROBO1 expression. Immunofluorescence analysis of rat facial-nerve nucleus samples verified that SLIT2 protein levels were significantly increased in the facial-nerve nuclei of injured samples. In conclusion, despite the fact that this study is primarily founded on animal models and despite notable differences existing between animals and humans in terms of the facial motor nucleus, this study successfully identified SLIT2 as potential therapeutic targets for PFP. The SLIT2-ROBO axis stands out as a particularly promising candidate. SLIT2 may play a role in modulating neuroimmune interactions and promoting nerve repair. These findings provide a foundation for future clinical studies and targeted interventions to enhance recovery from PFP. Future research should focus on human sample validation to enhance clinical translation.

Animals↗