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Mass spectrometry based proteomics profiling of human monocytes

Protein & Cell 2017年第2期8卷 123-133页

作者： Yong Zeng Fei-Yan Deng Wei Zhu Lan Zhang Hao He Chao Xu Qing Tian Ji-Gang Zhang Li-Shu Zhang Hong-Gang Hu Hong-Wen Deng College of Life Sciences and Bioengineering Beijing Jiaotong University Beijing 100044 China Center of Bioinformatics and Genomics Tulane University School of Public Health and Tropical Medicine New Orleans LA 70112 USA College of Life Sciences Hunan Normal University Changsha 410081 China Laboratory of Proteins and Proteomics Department of Epidemiology Soochow University School of Public Health Suzhou 205123 China

Human monocyte is an important cell type which is involved in various complex human diseases. To better understand the biology of human monocytes and facilitate further studies, we developed the first comprehensive proteome knowledge base specifically for human monocytes by integrating both in vivo and in vitro datasets. The top 2000 expressed genes from in vitro datasets and 779 genes from in vivo experiments were integrated into this study. Altogether, a total of 2237 unique monocyte-expressed genes were cataloged. Biological functions of these monocyte-expressed genes were annotated and classified via Gene Ontology （GO） analysis. Furthermore, by extracting the overlapped genes from in vivo and in vitro datasets, a core gene list including 541 unique genes was generated. Based on the core gene list, further gene-disease associations, pathway and network analyses were performed. Data analyses based on multiple bioinformatics tools produced a large body of biologically meaningful information, and revealed a number of genes such as SAMHDI, G6PD, GPD2 and EN01, which have been reported to be related to immune response, blood biology, bone remodeling, and cancer respectively. As a unique resource, this study can serve as a reference map for future in-depth research on monocytes biology and monocyte-involved human diseases.

关键词： human monocytes proteomics knowledgebase gene ontology gene-disease association network analysis

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Enhancing healthcare AI stability with edge computing and machine learning for extubation prediction

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Scientific Reports 2025年第1期15卷 1-11页

作者： Kuo-Yang Huang Ching-Hsiung Lin Che-Liang Chung Ying-Lin Hsu Huang-Chi Chen Ming-Hwarng Horng Ching-Sen Liu Jia-Lang Xu Division of Chest Medicine Department of Internal Medicine Changhua Christian Hospital Changhua Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung Taiwan Ph.D. Program in Medical Biotechnology National Chung Hsing University Taichung Taiwan Division of Chest Medicine Department of Internal Medicine Yuanlin Christian Hospital Changhua Taiwan Institute of Statistics National Chung Hsing University Taichung Taiwan Department of Applied Mathematics National Chung Hsing University Taichung Taiwan Department of Computer Science and Information Engineering Chaoyang University of Technology Taichung Taiwan

The advancement of the Internet of Medical Things (IoMT) has revolutionized data acquisition and processing in critical care settings. Given the pivotal role of ventilators, accurately predicting extubation outcomes is essential to optimize patient care. This study presents an edge computing-based framework that incorporates machine learning algorithms to predict ventilator extubation success using real-time data collected directly from ventilators. The system was deployed on edge devices to enable on-site inference with minimal latency. Among the evaluated models, Random Forest and XGBoost, the latter demonstrated superior predictive performance under both holdout and tenfold cross-validation schemes. Notably, the edge-based architecture reduced server data transmissions by 83.33%, while improving system stability, resilience, and sustainability. This paper details the model evaluation and demonstrates the feasibility and efficiency of edge intelligence in ventilator weaning decision support.

关键词： Clinical decision support system Edge-computing Extubation Internet of medical things Machine learning

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Noninvasive assessment of hydroquinidine effect in Brugada syndrome (QUIET BrS)

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Heart Rhythm 2025年

作者： Isbister, Julia C. Strocchi, Marina Riedy, Matthew Yeates, Laura Gray, Belinda Singer, Emma S. Bagnall, Richard D. Ingles, Jodie Raju, Hariharan Semsarian, Christopher Niederer, Steven A. Sy, Raymond W. Faculty of Medicine and Health University of Sydney Sydney NSW Australia Department of Cardiology Royal Prince Alfred Hospital Sydney NSW Australia National Heart and Lung Institute Imperial College London London United Kingdom School of Biomedical Engineering and Imaging Sciences King's College London London United Kingdom Medtronic Australasia Sydney NSW Australia Agnes Ginges Centre for Molecular Cardiology at Centenary Institute The University of Sydney Sydney NSW Australia Genomics and Inherited Disease Program Garvan Institute of Medical Research University of New South Wales Sydney NSW Australia Bioinformatics and Molecular Genetics Group at Centenary Institute The University of Sydney Sydney NSW Australia Faculty of Medicine Health and Human Sciences Macquarie University Sydney NSW Australia The Alan Turing Institute London United Kingdom

Background: Hydroquinidine reduces arrhythmic events in patients with Brugada syndrome (BrS). The mechanism by which it exerts antiarrhythmic benefit and its electrophysiological effects on BrS substrate remain incompletely understood. Objective: This study aimed to determine the effect of hydroquinidine on ventricular depolarization and repolarization in patients with BrS in vivo. Methods: Twelve patients with BrS underwent electrocardiography (standard, high-lead, and signal averaged) and electrocardiographic imaging at baseline and “on-treatment” with hydroquinidine 300 mg twice daily. ST-segment elevation, activation time, repolarization time, and activation-recovery interval (ARI) were computed for the ventricles and right ventricular outflow tract (RVOT). Serum hydroquinidine levels were determined, and adverse drug events were captured through a medication survey. Results: Hydroquinidine increased repolarization time (301.1 ± 24.1 ms vs 348.8 ± 28.3 ms;P<.001), repolarization gradients (1.1 ± 0.4 ms/mm vs 1.6 ± 0.4 ms/mm;P<0.001), and ARI (241.3 ± 18.1 ms vs 284.8 ± 21.5 ms;P<.001) in the RVOT, with a greater change in the RVOT than in the rest of the ventricles. In contrast, activation parameters did not change significantly on-treatment with hydroquinidine, although there was a subtle increase in ST-segment elevation over the RVOT (1.5 ± 0.7 mV vs 1.8 ± 0.8 mV;P<.001). Hydroquinidine levels did not correlate with electrophysiological changes or occurrence of adverse drug reactions. One patient developed frequent nonsustained ventricular tachycardia on-treatment with hydroquinidine. Conclusion: Hydroquinidine primarily affects ventricular repolarization and action potential duration (indicated by ARI) in patients with BrS and demonstrates regional variation with more significant changes in the RVOT. © 2024 Heart Rhythm Society

关键词： Activation-recovery interval Brugada syndrome Electrocardiographic imaging Hydroquinidine Noninvasive Ventricular activation Ventricular repolarization

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Worm Perturb-Seq: massively parallel whole-animal RNAi and RNA-seq

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Nature Communications 2025年第1期16卷 1-21页

作者： Hefei Zhang Xuhang Li Shivani Nanda Albertha J. M. Walhout Dongyuan Song Jingyi Jessica Li Onur Yukselen Alper Kucukural Manuel Garber Department of Systems Biology University of Massachusetts Chan Medical School Worcester MA USA Bioinformatics Interdepartmental Ph.D. Program University of California Los Angeles CA USA Department of Statistics and Data Science Department of Biostatistics Department of Computational Medicine and Department of Human Genetics University of California Los Angeles CA USA Via Scientific Inc. Cambridge MA USA Department of Genomics and Computational Biology University of Massachusetts Chan Medical School Worcester MA USA

Transcriptomes provide highly informative molecular phenotypes that, combined with gene perturbation, can connect genotype to phenotype. An ultimate goal is to perturb every gene and measure transcriptome changes, however, this is challenging, especially in whole animals. Here, we present ‘Worm Perturb-Seq (WPS)’, a method that provides high-resolution RNA-sequencing profiles for hundreds of replicate perturbations at a time in living animals. WPS introduces multiple experimental advances combining strengths of Caenhorhabditis elegans genetics and multiplexed RNA-sequencing with a novel analytical framework, EmpirDE. EmpirDE leverages the unique power of large transcriptomic datasets and improves statistical rigor by using gene-specific empirical null distributions to identify DEGs. We apply WPS to 103 nuclear hormone receptors (NHRs) and find a striking ‘pairwise modularity’ in which pairs of NHRs regulate shared target genes. We envision the advances of WPS to be useful not only for C. elegans, but broadly for other models, including human cells.

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The prospects and limitations of liquid biopsy utilization for clinical practice in Taiwan

The journal of liquid biopsy

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The journal of liquid biopsy 2025年 7卷 100290页

作者： Huei-Ying Li Chun-Chuan Chang Yu-Hsuan Yang Chi-Yuan Yao Jason Chia-Hsun Hsieh Shao-Hsuan Chang Medical Microbiota Center of the First Core Laboratory National Taiwan University Taipei Taiwan. Professional Master's Program of Biotechnology Management National Taiwan University Taipei Taiwan. Graduate Institute of Medical Genomics and Proteomics National Taiwan University Taipei Taiwan. Department of Laboratory Medicine National Taiwan University Hospital Taipei Taiwan. Division of Oncology Department of Internal Medicine Linkou Chang Gung Memorial Hospital Taoyuan Taiwan. College of Medicine Chang Gung University Taoyuan Taiwan. Department of Biomedical Engineering Chang Gung University Taoyuan Taiwan.

Objective:Liquid biopsy is a promising, non-invasive diagnostic tool for cancer, offering rapid and cost-effective genomic analysis. It provides a less invasive alternative to traditional tissue biopsies, with potential benefits in monitoring disease progression and detecting minimal residual disease (MRD). However, its clinical integration faces challenges, including utility assessment and workflow adaptation. This study evaluates the value of liquid biopsy in Taiwan from a clinical physician's perspective. Methods:A survey was conducted with 16 physicians specializing in thoracic medicine and hematologic oncology. Participants responded to a 5-point Likert scale to evaluate the timing of liquid biopsy adoption, willingness to incorporate it into clinical practice, and agreement on its role in managing specific clinical conditions. Results:Forty percent of physicians preferred liquid biopsy when tissue samples were unavailable. The inclusion of liquid biopsy under National Health Insurance (NHI) was a key factor in its adoption. Hematologic oncologists showed a stronger preference for liquid biopsy, particularly for MRD testing, compared to their counterparts in thoracic medicine (hematologic oncology vs. thoracic medicine: 4.2 ± 0.83 vs. 3.1 ± 0.60; p value = 0.01). Younger physicians valued turnaround time, while senior physicians prioritized test brand, with a focus on report speed. Conclusion:Physicians are generally less inclined to replace tissue biopsies with liquid biopsy, but hematologic oncologists show more flexibility. Test brand plays a role in physician decision-making, and the inclusion of liquid biopsy under NHI coverage is vital for its broader adoption in Taiwan.

关键词： Cancer diagnosis Clinical adoption Liquid biopsy Minimal residual disease (MRD) National health insurance

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PCC-hippocampal functional connectivity associated with stress biomarker changes after meditation training for healthy adults

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Neuroscience Letters 2025年 138272页

作者： Diane Joss Gunes Sevinc John W. Denninger Sat Bir Singh Khalsa Elizabeth A. Hoge Manoj Bhasin Jeffery A. Dusek Eric Macklin Towia A. Libermann Gregory L. Fricchione Herbert Benson Sara W. Lazar Department of Psychiatry Massachusetts General Hospital Boston MA USA Harvard Medical School Boston MA USA Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital Boston MA USA Department of Medicine Brigham and Women’s Hospital Harvard Medical School USA Department of Psychiatry Georgetown University Medical Center Washington DC USA Department of Biomedical Informatics Emory University School of Medicine Atlanta GA USA Susan Samueli Integrative Health Institute University of California-Irvine Irvine CA USA School of Medicine University of California-Irvine Irvine CA USA Genomics Proteomics Bioinformatics and Systems Biology Center Beth Israel Deaconess Medical Center Boston MA USA

Meditation training has been shown to improve physical and mental health and promote neural plasticity, but more research is needed on the relationships between these effects. This study analyzed the Resting State Functional Connectivity (RSFC) of posterior cingulate cortex (PCC) among 94 chronically stressed but otherwise healthy adults randomized 1:1:1 to receive eight weeks of in-person one-on-one interventions focused either on meditation (n = 32), yoga (n = 31), or stress education (n = 31). We found only in the meditation arm, there was a significant reduction of PCC RSFC with the left hippocampus ( p  < 0.05, FWE corrected). Post-intervention changes of PCC-hippocampal RSFC were significantly (all p  ≤ 0.01) correlated with changes of perceived stress ( r  = 0.54), allostatic load index ( r  = 0.58), and NF-κB anti-inflammatory gene expression ( r  = -0.55), suggesting the neural effects of meditation are closely associated with biomarkers of physical wellness. No significant changes with PCC RSFC were observed within the yoga or stress education arm, suggesting this neurobiological mechanism might be unique to meditation training.

关键词： Biomarker Inflammation MRI Meditation Wellbeing Wellness Yoga

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The roles of non-coding RNAs in cardiac regenerative medicine

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Non-coding RNA Research 2017年第2期2卷 100-110页

作者： Choong, Oi Kuan Lee, Desy S. Chen, Chen-Yun Hsieh, Patrick C.H. Taiwan International Graduate Program in Molecular Medicine National Yang-Ming University and Academia Sinica Taipei Taiwan Institute of Biomedical Sciences Academia Sinica Taipei 115 Taiwan Institute of Medical Genomics and Proteomics Institute of Clinical Medicine and Department of Surgery National Taiwan University & Hospital Taipei 100 Taiwan

The emergence of non-coding RNAs (ncRNAs) has challenged the central dogma of molecular biology that dictates that the decryption of genetic information starts from transcription of DNA to RNA, with subsequent translation into a protein. Large numbers of ncRNAs with biological significance have now been identified, suggesting that ncRNAs are important in their own right and their roles extend far beyond what was originally envisaged. ncRNAs do not only regulate gene expression, but are also involved in chromatin architecture and structural conformation. Several studies have pointed out that ncRNAs participate in heart disease;however, the functions of ncRNAs still remain unclear. ncRNAs are involved in cellular fate, differentiation, proliferation and tissue regeneration, hinting at their potential therapeutic applications. Here, we review the current understanding of both the biological functions and molecular mechanisms of ncRNAs in heart disease and describe some of the ncRNAs that have potential heart regeneration effects. © 2017 The Authors

关键词： Cardiac fate Cardiac regeneration Differentiation Non-coding RNAs Proliferation Reprograming

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Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants

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Science (New York, N.Y.) 2025年第6734期387卷 eadp4753页

作者： Liu, Hongbo Abedini, Amin Ha, Eunji Ma, Ziyuan Sheng, Xin Dumoulin, Bernhard Qiu, Chengxiang Aranyi, Tamas Li, Shen Dittrich, Nicole Chen, Hua-Chang Tao, Ran Tarng, Der-Cherng Hsieh, Feng-Jen Chen, Shih-Ann Yang, Shun-Fa Lee, Mei-Yueh Kwok, Pui-Yan Wu, Jer-Yuarn Chen, Chien-Hsiun Khan, Atlas Limdi, Nita A. Wei, Wei-Qi Walunas, Theresa L. Karlson, Elizabeth W. Kenny, Eimear E. Luo, Yuan Kottyan, Leah Connolly, John J. Jarvik, Gail P. Weng, Chunhua Shang, Ning Cole, Joanne B. Mercader, Josep M. Mandla, Ravi Majarian, Timothy D. Florez, Jose C. Haas, Mary E. Lotta, Luca A. Drivas, Theodore G. Vy, Ha My T Nadkarni, Girish N. Wiley, Laura K. Wilson, Melissa P. Gignoux, Christopher R. Rasheed, Humaira Thomas, Laurent F. Åsvold, Bjørn Olav Brumpton, Ben M. Hallan, Stein I. Hveem, Kristian Zheng, Jie Hellwege, Jacklyn N. Zawistowski, Matthew Zöllner, Sebastian Franceschini, Nora Hu, Hailong Zhou, Jianfu Kiryluk, Krzysztof Ritchie, Marylyn D. Palmer, Matthew Edwards, Todd L. Voight, Benjamin F. Hung, Adriana M. Susztak, Katalin Department of Medicine Renal Electrolyte and Hypertension Division University of Pennsylvania Philadelphia PA United States Institute of Diabetes Obesity and Metabolism University of Pennsylvania Philadelphia PA United States Department of Genetics University of Pennsylvania Philadelphia PA United States Penn-CHOP Kidney Innovation Center University of Pennsylvania Philadelphia PA United States Liangzhu Laboratory Zhejiang University 1369 West Wenyi Road Hangzhou Zhejiang China Department of Nephrology Children' Hospital Zhejiang University School of Medicine National Clinical Research Center for Child Health Hangzhou Zhejiang China Institute of Molecular Life Sciences HUN-REN Research Center for Natural Sciences Budapest Hungary Department of Molecular Biology Semmelweis University Budapest Hungary Department of Medicine Federal University of São Paulo São Paulo Brazil Department of Biostatistics Vanderbilt University Medical Center Nashville TN United States Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville TN United States Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Division of Nephrology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Institute of Biomedical Sciences Academia Sinica ROC Taipei Taiwan Cardiovascular Center Taichung Veterans General Hospital Taichung Taiwan ROC National Chung Hsing University Taichung Taiwan ROC Heart Rhythm Center Division of Cardiology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Department of Internal Medicine College of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Institute of Medicine Chung Shan Medical University Taichung Taiwan ROC Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan ROC Division of Endocrinology and Metabolism Department of Internal Medicine Kaohsiung Medical Universit

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the "Kidney Disease Genetic Scorecard" for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.

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A retinoic acid:YAP1 signaling axis controls atrial lineage commitment

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Cell Reports 2025年第5期44卷 115687页

作者： Abraham, Elizabeth Kostina, Aleksandra Volmert, Brett Roule, Thomas Huang, Ling Yu, Jingting Williams, April E. Megill, Emily Douglas, Aidan Pericak, Olivia M. Morris, Alex Stronati, Eleonora Larrinaga-Zamanillo, Arantza Fueyo, Raquel Zubillaga, Mikel Andrake, Mark D. Akizu, Naiara Aguirre, Aitor Estaras, Conchi Department of Cardiovascular Sciences Aging + Cardiovascular Discovery Center Lewis Katz School of Medicine Temple University Philadelphia 19140 PA United States Institute for Quantitative Health Science and Engineering Division of Developmental and Stem Cell Biology Michigan State University East Lansing 48824 MI United States Department of Biomedical Engineering College of Engineering Michigan State University East Lansing 48824 MI United States Raymond G. Perelman Center for Cellular and Molecular Therapeutics The Children's Hospital of Philadelphia Philadelphia 19104 PA United States Integrative Genomics and Bioinformatics Core Salk Institute for Biological Studies La Jolla 92037 CA United States Department of Child and Adolescence Psychiatry The Children's Hospital of Philadelphia Philadelphia 19104 PA United States Department of Chemical and Systems Biology Stanford University School of Medicine Stanford 94305 CA United States Cancer Epigenetics Institute Fox Chase Cancer Center Philadelphia 19111 PA United States Molecular Modeling Facility Program in Cancer Signaling and Microenvironment Fox Chase Cancer Center Philadelphia 19111 PA United States

In cardiac progenitor cells (CPCs), retinoic acid (RA) signaling induces atrial lineage gene expression and acquisition of an atrial cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified. To address this gap, we applied a functional genomics approach (i.e., scRNA-seq and snATAC-seq) to untreated and RA-treated human embryonic stem cell (hESC)-derived CPCs. Unbiased analysis revealed that the Hippo effectors YAP1 and TEAD4 are integrated with the atrial transcription factor enhancer network and that YAP1 activates RA enhancers in CPCs. Furthermore, Yap1 deletion in mouse embryos compromises the expression of RA-induced genes, such as Nr2f2, in the CPCs of the second heart field. Accordingly, in hESC-derived patterned heart organoids, YAP1 regulates the formation of an atrial chamber but is dispensable for the formation of a ventricle. Overall, our findings revealed that YAP1 cooperates with RA signaling to induce atrial lineages during cardiogenesis. © 2025 The Author(s)

关键词： atrial differentiation cardiac enhancers cardiac progenitors chamber development CP: Developmental biology heart organoids NR2F2 retinoic acid signaling SHF TEAD4 YAP1

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Sorbate induces lysine sorbylation through noncanonical activities of class I HDACs to regulate the expression of inflammation genes

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Science Advances 2025年第22期11卷

作者： Yi-Cheng Sin Breann Abernathy Zuo-fei Yuan Jason L. Heier Justin E. Gonzalez Laurie L. Parker Douglas G. Mashek Yue Chen Department of Biochemistry Molecular Biology and Biophysics University of Minnesota Twin Cities Minneapolis MN USA. Bioinformatics and Computational Biology Program University of Minnesota Twin Cities Minneapolis MN USA. Center for Proteomics and Metabolomics St. Jude Children’s Research Hospital Memphis TN USA. Department of Medicine Division of Diabetes Endocrinology and Metabolism University of Minnesota Twin Cities Minneapolis MN USA. Institute for the Biology of Aging and Metabolism University of Minnesota Twin Cities Minneapolis MN USA.

Environmental factors may affect gene expression through epigenetic modifications of histones and transcription factors. Here, we report that cellular uptake of sorbate, a common food preservative, induces lysine sorbylation (Ksor) in mammalian cells and tissue mediated by the noncanonical activities of class I histone deacetylases (HDAC1-3). We demonstrated that HDAC1-3 catalyze sorbylation upon sorbate uptake and desorbylation in the absence of sorbate both in vitro and in cells. Sorbate uptake in mice livers significantly induced histone Ksor, correlating with decreased expressions of inflammation-response genes. Accordingly, sorbate treatment in macrophage RAW264.7 cells upon lipopolysaccharide (LPS) stimulation dose-dependently down-regulated proinflammatory gene expressions and nitric oxide production. Proteomic profiling identified RelA, a component of the NF-κB complex, and its interacting proteins as bona fide Ksor targets and sorbate treatment significantly decreased NF-κB transcriptional activities in response to LPS stimulation in RAW264.7 cells. Together, our study demonstrated a noncanonical mechanism of sorbate uptake in regulating epigenetic histone modifications and inflammatory gene expression.

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