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arXiv 2017年

作者： Sengupta, Subhajit Pal, Subhadip Mitra, Riten Guo, Ying Banerjee, Arunava Ji, Yuan Program for Computational Genomics and Medicine NorthShore University HealthSystem Department of Bioinformatics and Biostatistics University of Louisville Department of Biostatistics and Bioinformatics Emory University Department of Computer and Information Science and Engineering University of Florida Department of Public Health Sciences University of Chicago

Analysis of a Bayesian mixture model for the Matrix Langevin distribution on the Stiefel manifold is presented. The model exploits a particular parametrization of the Matrix Langevin distribution, various aspects of which are elaborated on. A general, and novel, family of conjugate priors, and an efficient Markov chain Monte Carlo (MCMC) sampling scheme for the corresponding posteriors is then developed for the mixture model. Theoretical properties of the prior and posterior distributions, including posterior consistency, are explored in detail. Extensive simulation experiments are presented to validate the efficacy of the framework. Real-world examples, including a large scale neuroimaging dataset, are analyzed to demonstrate the computational tractability of the approach. Copyright © 2017, The Authors. All rights reserved.

关键词： Mixtures

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Evaluation of using WGS/WES to characterize ACMG actionable genes in genetic testing reports

Evaluation of using WGS/WES to characterize ACMG actionable ...

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2021 IEEE International Conference on bioinformatics and Biomedicine, BIBM 2021

作者： Yang, Wen-Tse Wu, Dong-Chi Liu, Jen-Feng Hong, Jin-Bon Wu, June-Tai Chen, Pei-Lung Chen, Chien-Yu National Taiwan University Department of Biomechatronics Engineering Taipei Taiwan National Taiwan University and Academia Sinica Genome and Systems Biology Degree Program Taipei Taiwan Institute of Molecular Medicine National Taiwan University College of Medicine Taipei Taiwan National Taiwan University Hospital Department of Dermatology Taipei Taiwan Graduate Institute of Medical Genomics and Proteomics National Taiwan University College of Medicine Taipei Taiwan

ISBN: (纸本)9781665401265

Since the American College of Medical Genetics and genomics (ACMG) published recommendations for reporting incidental findings in clinical exome and genome sequencing in 2013, the list of suggested actionable genes appear more and more frequently in the reports of genetic testing. However, the existence of low-coverage regions, no matter happening systematically or randomly, in whole genome sequencing (WGS) or whole exome sequencing (WES) raise the chances of false negatives when reporting pathogenicity in variant discovery. To evaluate the effectivity of different sequencing methods, this study developed a workflow to examine low-coverage regions in ACMG actionable genes (version 2 contains 59 genes) on three groups of sequencing data, including 5 samples of 30X WGS, 41 samples of 40X WGS, and 11 samples of WES. By extracting the ACMG regions of the alignment files, we first found that per-base mean coverage in WES is significantly higher in some chromosomes (2, 5, 6, 9, 13, 14, 17, 18) than the others, and the overall average (44.5) is higher than 30X WGS (32.4) and 40X WGS (36.2). However, the total length of the low-coverage regions in ACMG actionable genes is higher in WES samples: 23 times higher than 40X WGS, and 8 times higher than 30X WGS. When looking into ClinVar significance of pathogenic/likely pathogenic (P/LP) variants (the 2020/03/16 release contains 21,388 P/LP variants falling in the 59 actionable genes), 100% (11/11) WES samples and 80% (4/5) 30X WGS samples have more than 20 P/LP variants in the low-coverage regions, while only 2.4% (1/41) 40X WGS samples have such a risk of missing >20 P/LP variants. We conclude that in order to reduce the possibility of missing clinically significant variants, 40X WGS are more recommended than 30X WGS and WES to achieve satisfied quality of characterizing ACMG actionable genes in genetic testing. © 2021 IEEE.

关键词： Genome

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Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation (vol 21, pg 432, 2018)

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NATURE NEUROSCIENCE 2018年第7期21卷 1015-1015页

作者： Preissl, Sebastian Fang, Rongxin Huang, Hui Zhao, Yuan Raviram, Ramya Gorkin, David U. Zhang, Yanxiao Sos, Brandon C. Afzal, Veena Dickel, Diane E. Kuan, Samantha Visel, Axel Pennacchio, Len A. Zhang, Kun Ren, Bing Ludwig Institute for Cancer Research La Jolla CA USA Center for Epigenomics Department of Cellular and Molecular Medicine University of California San Diego School of Medicine La Jolla CA USA Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA USA Biomedical Sciences Graduate Program University of California San Diego La Jolla CA USA Department of Bioengineering University of California San Diego La Jolla CA USA Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley CA USA US Department of Energy Joint Genome Institute Walnut Creek CA USA School of Natural Sciences University of California Merced Merced CA USA Comparative Biochemistry Program University of California Berkeley Berkeley CA USA Institute of Genomic Medicine Moores Cancer Center University of California San Diego School of Medicine La Jolla CA USA

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.

关键词： Cell type diversity Chromatin Chromatin analysis Epigenomics

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Distinct adipose progenitor cells emerging with age drive active adipogenesis

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Science (New York, N.Y.) 2025年第6745期388卷 eadj0430页

作者： Wang, Guan Li, Gaoyan Song, Anying Zhao, Yutian Yu, Jiayu Wang, Yifan Dai, Wenting Salas, Martha Qin, Hanjun Medrano, Leonard Dow, Joan Li, Aimin Armstrong, Brian Fueger, Patrick T. Yu, Hua Zhu, Yi Shao, Mengle Wu, Xiwei Jiang, Lei Campisi, Judith Yang, Xia Wang, Qiong A. Department of Molecular and Cellular Endocrinology Arthur Riggs Diabetes and Metabolism Research Institute City of Hope Medical Center Duarte CA USA Department of Integrative Biology and Physiology University of California Los Angeles CA United States Light Microscopy Core City of Hope Medical Center Duarte CA USA The Integrative Genomics Core City of Hope Medical Center Duarte CA USA Division of Developmental and Translational Diabetes and Endocrinology Research City of Hope Medical Center Duarte CA USA Comprehensive Metabolic Phenotyping Core City of Hope Medical Center Duarte CA USA Pathology Core of Shared Resources City of Hope Medical Center Duarte CA USA Comprehensive Cancer Center Beckman Research Institute City of Hope Medical Center Duarte CA USA Children's Nutrition Research Center Department of Pediatrics Baylor College of Medicine Houston TX United States Key Laboratory of Immune Response and Immunotherapy Shanghai Institute of Immunity and Infection Chinese Academy of Sciences Shanghai China Buck Institute for Research on Aging Novato CA United States Bioinformatics Interdepartmental Program University of California Los Angeles CA United States Institute for Quantitative and Computational Biosciences University of California Los Angeles CA United States Molecular and Medical Pharmacology University of California Los Angeles CA United States

Starting at middle age, adults often suffer from visceral adiposity and associated adverse metabolic disorders. Lineage tracing in mice revealed that adipose progenitor cells (APCs) in visceral fat undergo extensive adipogenesis during middle age. Thus, despite the low turnover rate of adipocytes in young adults, adipogenesis is unlocked during middle age. Transplantations quantitatively showed that APCs in middle-aged mice exhibited high adipogenic capacity cell-autonomously. Single-cell RNA sequencing identified a distinct APC population, the committed preadipocyte, age-enriched (CP-A), emerging at this age. CP-As demonstrated elevated proliferation and adipogenesis activity. Pharmacological and genetic manipulations indicated that leukemia inhibitory factor receptor signaling was indispensable for CP-A adipogenesis and visceral fat expansion. These findings uncover a fundamental mechanism of age-dependent adipose remodeling, offering critical insights into age-related metabolic diseases.

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Importance of surface charge of soot nanoparticles in determining inhalation toxicity in mice

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Environmental Science and Pollution Research 2023年第7期30卷 18985-18997页

作者： Hsiao, Ta-Chih Han, Chia-Li Yang, Tzu-Ting Lee, Yueh-Lun Shen, Yu-Fang Jheng, Yu-Teng Lee, Chii-Hong Chang, Jer-Hwa Chung, Kian Fan Kuo, Han-Pin Chuang, Hsiao-Chi Graduate Institute of Environmental Engineering National Taiwan University Taipei Taiwan Master Program in Clinical Genomics and Proteomics College of Pharmacy Taipei Medical University Taipei Taiwan Department of Environmental Engineering and Health Yuanpei University of Medical Technology Hsin Chu City Taiwan Department of Microbiology and Immunology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Environmental Engineering National Center University Tauyoun Taiwan Genome and Systems Biology Degree Program Academia Sinica and National Taiwan University Taipei Taiwan Department of Pathology Taipei City Hospital Heping Fuyou Branch Taipei Taiwan School of Respiratory Therapy College of Medicine Taipei Medical University Taipei Taiwan Division of Pulmonary Medicine Department of Internal Medicine Wan Fang Hospital Taipei Medical University Taipei Taiwan National Heart and Lung Institute Imperial College London London United Kingdom Division of Pulmonary Medicine Department of Internal Medicine School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Division of Pulmonary Medicine Department of Internal Medicine Shuang Ho Hospital Taipei Medical University New Taipei City Taiwan Cell Physiology and Molecular Image Research Center Wan Fang Hospital Taipei Medical University Taipei Taiwan

Physicochemical properties of nanoparticles are important in regulating nanoparticle toxicity;however, the contribution of nanoparticle charge remains unclear. The objective of this study was to investigate the pulmonary effects of inhalation of charged soot nanoparticles. We established a stably charged nanoparticle generation system for whole-body exposure in BALB/c mice, which produced positively charged, negatively charged, and neutral soot nanoparticles in a wide range of concentrations. After a 7-day exposure, pulmonary toxicity was assessed, together with proteomics analysis. The charged soot nanoparticles on average carried 1.17–1.35 electric charges, and the sizes for nanoparticles under different charging conditions were all fixed at 69 ~ 72 nm. We observed that charged soot nanoparticles induced cytotoxic LDH and increased lung permeability, with the release of 8-isoprostane and caspase-3 and systemic IL-6 in mice, especially for positively charged soot nanoparticles. Next, we observed that positive-charged soot nanoparticles upregulated Eif2, Eif4, sirtuin, mammalian target of rapamycin (mTOR), peroxisome proliferator-activated receptors (PPAR), and HIPPO-related signaling pathways in the lungs compared with negatively charged soot nanoparticles. HIF1α, sirt1, E-cadherin, and Yap were increased in mice’s lungs by positively charged soot nanoparticle exposure. In conclusion, carbonaceous nanoparticles carrying electric ions, especially positive-charged, are particularly toxic when inhaled and should be of concern in terms of pulmonary health protection. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

关键词： Nanoparticles

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Genome-wide analyses identify 30 loci associated with obsessive–compulsive disorder

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Nature Genetics 2025年 1-13页

作者： Strom, Nora I. Gerring, Zachary F. Galimberti, Marco Yu, Dongmei Halvorsen, Matthew W. Abdellaoui, Abdel Rodriguez-Fontenla, Cristina Sealock, Julia M. Bigdeli, Tim Coleman, Jonathan R. Mahjani, Behrang Thorp, Jackson G. Bey, Katharina Burton, Christie L. Luykx, Jurjen J. Zai, Gwyneth Alemany, Silvia Andre, Christine Askland, Kathleen D. Bäckman, Julia Banaj, Nerisa Barlassina, Cristina Nissen, Judith Becker Bienvenu, O. Joseph Black, Donald Bloch, Michael H. Børte, Sigrid Bosch, Rosa Breen, Michael Brennan, Brian P. Brentani, Helena Buxbaum, Joseph D. Bybjerg-Grauholm, Jonas Byrne, Enda M. Cabana-Dominguez, Judit Camarena, Beatriz Camarena, Adrian Cappi, Carolina Carracedo, Angel Casas, Miguel Cavallini, Maria Cristina Ciullo, Valentina Cook, Edwin H. Crosby, Jesse Cullen, Bernadette A. De Schipper, Elles J. Delorme, Richard Djurovic, Srdjan Elias, Jason A. Estivill, Xavier Falkenstein, Martha J. Fundin, Bengt T. Garner, Lauryn Gironda, Christina Goes, Fernando S. Grados, Marco A. Grove, Jakob Guo, Wei Haavik, Jan Hagen, Kristen Harrington, Kelly Havdahl, Alexandra Höffler, Kira D. Hounie, Ana G. Hucks, Donald Hultman, Christina Janecka, Magdalena Jenike, Eric Karlsson, Elinor K. Kelley, Kara Klawohn, Julia Krasnow, Janice E. Krebs, Kristi Lange, Christoph Lanzagorta, Nuria Levey, Daniel Lindblad-Toh, Kerstin Macciardi, Fabio Maher, Brion Mathes, Brittany McArthur, Evonne McGregor, Nathaniel McLaughlin, Nicole C. Meier, Sandra Miguel, Euripedes C. Mulhern, Maureen Nestadt, Paul S. Nurmi, Erika L. O’Connell, Kevin S. Osiecki, Lisa Ousdal, Olga Therese Palviainen, Teemu Pedersen, Nancy L. Piras, Federica Potluri, Sriramya Rabionet, Raquel Ramirez, Alfredo Rauch, Scott Reichenberg, Abraham Riddle, Mark A. Ripke, Stephan Rosário, Maria C. Sampaio, Aline S. Schiele, Miriam A. Skogholt, Anne Heidi Sloofman, Laura G. Smit, Jan Artigas, María Soler Thomas, Laurent F. Tifft, Eric Vallada, Homero van Kirk, Nathanial Veenstra-VanderWeele, Jeremy Vulink, Nienke N. Walker, Christopher P. Wang, Ying Wendland, Jens R. Winsvold Department of Psychology Humboldt-Universität zu Berlin Berlin Germany Department of Psychiatric Phenomics and Genomics (IPPG) Ludwig-Maximilians University Munich Munich Germany Centre for Psychiatry Research Department of Clinical Neuroscience Karolinska Institutet and Stockholm Health Services Region Stockholm Stockholm Sweden Department of Biomedicine Aarhus University Aarhus Denmark University Hospital of Psychiatry and Psychotherapy University of Bern Bern Switzerland Department of Mental Health and Neuroscience Translational Neurogenomics QIMR Berghofer Medical Research Institute Brisbane QLD Australia Department of Population Health and Immunity Healthy Development and Ageing Walter and Eliza Hall Institute of Medical Research Melbourne VIC Australia Department of Psychiatry Human Genetics Yale University New Haven CT United States VA Connecticut Healthcare System West Haven CT United States Department of Center for Genomic Medicine Psychiatric and Neurodevelopmental Genetics Unit Massachusetts General Hospital Boston MA United States Stanley Center for Psychiatric Research Broad Institute of MIT and Harvard Cambridge MA United States Department of Genetics University of North Carolina at Chapel Hill Chapel Hill NC United States Department of Psychiatry Amsterdam University Medical Centers University of Amsterdam Amsterdam Netherlands Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) Genomics and Bioinformatics University of Santiago de Compostela Santiago de Compostela Spain Grupo de Medicina Xenómica Genetics Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS) Santiago de Compostela Spain Vanderbilt Genetics Institute Vanderbilt University Nashville TN United States Department of Psychiatry and Behavioral Sciences SUNY Downstate Health Sciences University Brooklyn NY United States VA NY Harbor Healthcare System Brooklyn NY United States Social Genetic and Developmental Psychiatry Centre Insti

Obsessive–compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that ~11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D₁ and D₂ type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index. © The Author(s) 2025.

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Author Correction: LILRB3 genetic variation is associated with kidney transplant failure in African American recipients

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Nature medicine 2025年 2025 Apr 15页

作者： Zeguo Sun Zhengzi Yi Chengguo Wei Wenlin Wang Tianyuan Ren Paolo Cravedi Fasika Tedla Stephen C Ward Evren Azeloglu Daniel R Schrider Yun Li Atlas Khan Francesca Zanoni Jia Fu Sumaria Ali Shun Liu Deguang Liang Tong Liu Hong Li Caixia Xi Thi Ha Vy Gohar Mosoyan Quan Sun Ashwani Kumar Zhongyang Zhang Samira Farouk Kirk Campell Jordi Ochando Kyung Lee Steve Coca Jenny Xiang Patricia Connolly Lorenzo Gallon Philip J O'Connell Robert Colvin Madhav C Menon Girish Nadkarni John C He Monica Kraft Xuejun Jiang Xuewu Zhang Krzysztof Kiryluk Aravind Cherukuri Fadi G Lakkis Weiguo Zhang Shu-Hsia Chen Peter S Heeger Weijia Zhang Renal Division Department of Medicine Icahn School of Medicine at Mount Sinai New York NY USA. Suzhou Institute of Systems Medicine Chinese Academy of Medical Sciences Suzhou China. The Recanati/Miller Transplantation Institute Icahn School of Medicine at Mount Sinai New York NY USA. Department of Pathology and Laboratory Medicine Icahn School of Medicine at Mount Sinai New York NY USA. Department of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USA. Division of Nephrology Department of Medicine Columbia University New York NY USA. Center for Immunotherapy Research Houston Methodist Neal Cancer Center and Houston Methodist Research Institute Houston TX USA. Department of Pharmacology University of Texas Southwestern Medical Center Dallas TX USA. Cell Biology Program Memorial Sloan Kettering Cancer Center New York NY USA. Center for Advanced Proteomics Research and Department of Microbiology Biochemistry and Molecular Genetics Rutgers University Newark NJ USA. Department of Medicine Yale University New Haven CT USA. Department of Genetics and Genomics Icahn School of Medicine at Mount Sinai New York NY USA. Department of Oncological Sciences Icahn School of Medicine at Mount Sinai New York NY USA. Department of Microbiology and Immunology Weil Cornell Medicine New York NY USA. VericiDx Inc. Franklin TN USA. Department of Medicine University of Illinois Chicago Chicago IL USA. Centre for Transplant and Renal Research Westmead Institute for Medical Research University of Sydney Sydney New South Wales Australia. Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA. Department of Medicine Icahn School of Medicine at Mount Sinai New York NY USA. Departments of Surgery Immunology and Medicine University of Pittsburgh School of Medicine Pittsburgh PA USA. Department of Medicine Cedars-Sinai Medical Center Los Angeles CA USA. Renal Division Department of Medicine Icahn S

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Current Progress of COPD Early Detection: Key Points and Novel Strategies

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International Journal of COPD 2023年 18卷 1511-1524页

作者： Lin, Ching-Hsiung Cheng, Shih-Lung Chen, Chiung-Zuei Chen, Chia-Hung Lin, Sheng-Hao Wang, Hao-Chien Division of Chest Medicine Changhua Christian Hospital Changhua 500 Taiwan Institute of Genomics and Bioinformatics National Chung Hsing University Taichung 402 Taiwan Ph.D. Program in Translational Medicine National Chung Hsing University Taichung Taiwan Department of Recreation and Holistic Wellness MingDao University Changhua Taiwan Department of Internal Medicine Far Eastern Memorial Hospital Taipei 220 Taiwan Department of Chemical Engineering and Materials Science Yuan Ze University Taoyuan 320 Taiwan Division of Pulmonary Medicine Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Division of Pulmonary and Critical Care Medicine Department of Internal Medicine China Medical University Hospital Taichung 404 Taiwan Department of Internal Medicine National Taiwan University Hospital Taipei 100 Taiwan

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, with approxi-mately 70% to 80% of adults with COPD being undiagnosed. Patients with undiagnosed COPD are at increased risk of poor outcomes and a worsened quality of life, making early detection a crucial strategy to mitigate the impact of COPD and reduce the burden on healthcare systems. In the past decade, increased interest has been focused on the development of effective strategies and instrument for COPD early detection. However, identifying undiagnosed cases of COPD is still challenging. Both screening and case-finding approaches have been adopted to identify undiagnosed COPD, with case-finding being recommended by the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline and the updated United States Preventive Services Task Force (USPTF) recommendation. Nonetheless, the approaches, criteria, and instruments used for early detection of COPD are varied. However, advances in the taxonomy and risk factors of COPD are continuously being investigated. It is important to continuously assess the current state of knowledge on COPD early detection, given the challenges associated with identifying undiagnosed COPD. This review aims to highlight recent advances in early detection of COPD. To discuss the current challenge and opportunity in COPD early detection, providing an overview of existing literature on COPD case-finding strategies, including the approaches, criteria for subjects, and instruments. The review also summarizes the current progress in COPD case-findings and proposes a COPD case-finding flowchart as an efficient method for identifying at risk COPD patients. © 2023 Lin et al.

关键词： at-risk case-finding COPD early detection undiagnosed

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The correlations between oxidative stress markers and indoor volatile organic compounds among the general population in Ansan and Incheon cities, Korea

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Toxicology and Environmental Health Sciences 2009年第1期1卷 37-48页

作者： Hong, Eunyoung Lee, Eunil Kim, Yanghee Oh, Eunha Kim, Young Whan Moon, Kyoung Whan Choi, Jae Wook Lee, Junghwa Roh, JooYoung Dept. of Preventive Med. and Medical Res. Center for Environmental Toxico-Genomics and Proteomics Korea University Seoul South Korea Department of Public Health School of Medicine Graduate School of Medicine Korea University Seoul South Korea Cellular and Developmental Biology Division of Brain Korea 21 Program for Biomedical Science Graduate School Korea University Seoul South Korea Department of Environmental Health Science School of Public Health Korea University Seoul South Korea Department of Environmental Health Science College of Health Sciences Korea University Seoul South Korea Department of Pediatrics College of Medicine Korea University Seoul South Korea Department of Dermatology Gachon Univeristy of Medicine Gil Medical Center Incheon South Korea

Indoor VOC and aldehydes may increase oxidative stress for home dwellers. Our study aim was to determine the correlations between oxidative stress markers in subjects and exposure to VOC and aldehydes in homes. Among ninety five control subjects in Ansan and Incheon (South Korea), blood samples were collected for evaluation of total antioxidant capacity, malondialdehyde (MDA) in plasma, protein carbonyl, and DNA damage of lymphocytes. Indoor VOC and aldehydes were measured in the homes of the subjects. A partial correlation analysis was performed to assess the association between oxidative stress markers and VOC/aldehydes with adjustment for formaldehyde levels. There were significant correlations between the total antioxidant capacity and some chemicals, including heptanes, α-pinene, β-pinene, and decanal in the young age (10-19 years) group. The many correlations between VOC/aldehydes and DNA damage expressed as the Olive tail moment showed statistically significant in the middle (20-39 years) and older age (40-59 years) groups, but not in the young age group. These correlation could not account for the exposure to specific chemicals being related to an increase in DNA damage because most VOC/aldehydes were highly correlate exac other except some chemicals. In conclusion, we found that DNA damage of T- and B-lymphocytes evaluated by the Comet assay could be sensitive oxidative stress markers to evaluate the human response to VOC/ aldehydes exposure in middle and older age groups. Our study also showed that age affected the association between VOC/aldehydes exposure and oxidative stress markers including DNA damage and antioxidants. However, further studies are needed to confirm these correlations in a larger number of subjects because of limitations of this study, including a lack of personal exposure. © 2009 The Korean Society of Environmental Risk Assessment and Health Science and Springer.

关键词： Comet assay DNA damage Formaldehyde Indoor air pollution Organic compounds Oxidative stress

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APIR:Aggregating Universal proteomics Database Search Algorithms for Peptide Identification with FDR Control

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genomics, proteomics & bioinformatics 2024年第2期22卷 171-187页

作者： Yiling Elaine Chen Xinzhou Ge Kyla Woyshner MeiLu McDermott Antigoni Manousopoulou Scott B.Ficarro Jarrod A.Marto Kexin Li Leo David Wang Jingyi Jessica Li Department of Statistics and Data Science University of CaliforniaLos AngelesCA 90095USA Department of Immuno-Oncology Beckman Research InstituteCity of Hope National Medical CenterDuarteCA 91010USA Department of Quantitative and Computational Biology University of Southern CaliforniaLos AngelesCA 90089USA Department of Cancer Biology and Blais Proteomics Center Dana-Farber Cancer InstituteDepartment of PathologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA 02215USA Department of Pediatrics City of Hope National Medical CenterDuarteCA 91010USA Bioinformatics Interdepartmental Program University of CaliforniaLos AngelesCA 90095USA Department of Human Genetics University of CaliforniaLos AngelesCA 90095USA Department of Computational Medicine University of CaliforniaLos AngelesCA 90095USA Department of Biostatistics University of CaliforniaLos AngelesCA 90095USA

Advances in mass spectrometry(MS)have enabled high-throughput analysis of proteomes in biological *** state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide–spectrum matches(PSMs),which convert mass spectra to peptide *** database search algorithms use distinct search strategies and thus may identify unique ***,no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and a control on the false discovery rate(FDR).To fill in this gap,we proposed a statistical framework,Aggregation of Peptide Identification Results(APIR),that is universally compatible with all database search ***,under an FDR threshold,APIR is guaranteed to identify at least as many,if not more,peptides as individual database search algorithms *** of APIR on a complex proteomics standard dataset showed that APIR outpowers individual database search algorithms and empirically controls the *** data studies showed that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search *** APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis,e.g.,differential gene expression analysis on RNA sequencing *** APIR R package is available at https://***/yiling0210/APIR.

关键词： Shotgun proteomics Peptide–spectrum match Peptide identification Aggregation of lists FDR control

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