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LOW-FREQUENCY VARIANT IMPUTATION IDENTIFIES NOVEL DISEASE-ASSOCIATED LOCI IN A GENOME-WIDE ASSOCIATION STUDY OF LATE-ONSET ALZHEIMER'S DISEASE

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Alzheimer's & Dementia 2014年第4期10卷 P135-P135页

作者： Brian W. Kunkle Adam C. Naj Kara Hamilton-Nelson William R. Perry Amanda Partch Otto Valladares Jaeyoon Chung Gyungah Jun Mike Schmidt Gary Beecham Li-San Wang Eden Martin Richard Mayeux Jonathan Haines Lindsay A. Farrer Gerard D. Schellenberg Margaret Pericak-Vance University of Miami Hussman Institute for Human Genomics Miami Florida United States University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania United States University of Miami Miami Florida United States University of Pennsylvania Philadelphia Pennsylvania United States Boston University Bioinformatics Graduate Program Boston Massachusetts United States Boston University School of Medicine Boston Massachusetts United States University of Pennsylvania School of Medicine Philadelphia Pennsylvania United States Columbia University New York New York United States Case Western Reserve University Cleveland Ohio United States

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The Association of Plasma Biomarkers and Survival in the Oldest Old

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Alzheimer's & Dementia 2023年第S14期19卷

作者： Linda M.C. Lorenz Niccoló Tesi Sven J van der Lee Marc Hulsman Mariam Gouda Sietske A.M. Sikkes Charlotte E. Teunissen Henne Holstege Section Genomics of Neurodegenerative Diseases and Aging Department of Clinical Genetics Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam Netherlands Genomics of Neurodegenerative Diseases and Aging Human Genetics Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam The Netherlands Amsterdam Netherlands Alzheimer Center Amsterdam Department of Neurology Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam Netherlands Correspondece Delft University of Technology Delft Netherlands Genomics of Neurodegenerative Diseases and Aging Human Genetics Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam Netherlands Alzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam Netherlands Amsterdam Neuroscience Neurodegeneration Amsterdam Netherlands Genomics of Neurodegenerative Diseases and Aging Human Genetics Vrije Universiteit Amsterdam Amsterdam UMC location VUmc Amsterdam Amsterdam Netherlands 3. Delft Bioinformatics Lab Delft University of Technology Delft The Netherlands Delft Netherlands Alzheimer Centre Department of Neurology Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam The Netherlands Amsterdam Netherlands Neurochemistry Laboratory Department of Clinical Chemistry Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam Netherlands Amsterdam UMC location VUmc Amsterdam Netherlands Faculty of Behavioural and Movement Sciences Clinical Developmental Psychology & Clinical Neuropsychology Vrije Universiteit Amsterdam Amsterdam Netherlands Department of Epidemiology and Biostatistics VU University Medical Center Amsterdam Netherlands Neurochemistry Laboratory Department of Clinical Chemistry Amsterdam Neuroscience Program Neurodegeneration Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands Amsterdam Netherlands Delft Bioinformatics Lab Delft University of Technology Delft The

Background Previous research showed that plasma NfL (neurofilament light chain) associated with survival. Here we perform exploratory analyses to associate a broader range of plasma biomarkers Amyloid-βeta-40 (Aβ 40 ) , Amyloid-βeta-42 (Aβ 42 ), phosphorylated Tau-181 (pTau-181), NfL and glial fibrillary acidic protein (GFAP), with survival after reaching 100 years. Method The longitudinal Dutch 100-plus study cohort comprises of self-reported cognitively healthy centenarians. Biomarkers were measured in 202 centenarians (137 females, ISCED education level median [IQR] 3 [2–4]) on the Simoa platform. Information on survival was obtained via family report until January 2023. Centenarians who were alive were censored at date of last visit or date last confirmed alive. We investigated the relationship between biomarkers and survival by cox regression analyses, adjusting for age at blood draw, sex and cognitive functioning. We performed maximally selected log-rank statistics between all plasma biomarkers and survival rate to find an optimal cut-off, and constructed Kaplan-Meier survival curves. Result Of 202 centenarians (median age [IQR] at blood draw 101.4 [100.4-102.9]), 173 (85.6%) were deceased (median age [IQR] at death 103.2 [102.0-104.3]). The median (IQR) survival time after blood draw was 14.4 (5.5-25.1) months. All biomarkers Aβ 40 , Aβ 42 , pTau-181, NfL and GFAP intercorrelated (r s = 0.17–0.79; all P -values<0.05). Cox regression analyses showed that for each standard deviation increase in NfL, adjusted for age, sex, and MMSE score, the risk of mortality increased by 28% (HR 1.28; 95% CI, 1.11–1.47; P <0.001), Table 1. Maximally selected log-rank statistics split up NfL into survival groups high and low (cut-off 70.34 pg/mL, M = 3.803, P = 0.003, Figure 1). The median (IQR) shorter survival time of high versus low NfL was 7.8 (5.38-9.27) months. No statistically significant cut-off values were identified for the remaining biomarkers. Conclusion Our results

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A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration

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Cell genomics 2023年第6期3卷 100302-100302页

作者： Orozco, Luz D. Owen, Leah A. Hofmann, Jeffrey Stockwell, Amy D. Tao, Jianhua Haller, Susan Mukundan, Vineeth T. Clarke, Christine Lund, Jessica Sridhar, Akshayalakshmi Mayba, Oleg Barr, Julie L. Zavala, Rylee A. Graves, Elijah C. Zhang, Charles Husami, Nadine Finley, Robert Au, Elizabeth Lillvis, John H. Farkas, Michael H. Shakoor, Akbar Sherva, Richard Kim, Ivana K. Kaminker, Joshua S. Townsend, Michael J. Farrer, Lindsay A. Yaspan, Brian L. Chen, Hsu-Hsin DeAngelis, Margaret M. Department of Bioinformatics and Computational Biology Genentech South San Francisco 94080 CA United States Department of Ophthalmology and Visual Sciences University of Utah School of Medicine The University of Utah Salt Lake City 84132 UT United States Department of Population Health Sciences University of Utah School of Medicine The University of Utah Salt Lake City 84132 UT United States Department of Obstetrics and Gynecology University of Utah School of Medicine The University of Utah Salt Lake City 84132 UT United States Department of Ophthalmology Ross Eye Institute Jacobs School of Medicine and Biomedical Sciences State University of New York University at Buffalo Buffalo 14203 NY United States Department of Pathology Genentech South San Francisco 94080 CA United States Department of Human Genetics Genentech South San Francisco 94080 CA United States Departments of Microchemistry Proteomics and Lipidomics Genentech South San Francisco 94080 CA United States Department of Human Pathobiology & OMNI Reverse Translation Genentech South San Francisco 94080 CA United States Neuroscience Graduate Program Jacobs School of Medicine and Biomedical Sciences State University of New York University at Buffalo Buffalo 14203 NY United States Department of Biochemistry Jacobs School of Medicine and Biomedical Sciences State University of New York University at Buffalo Buffalo 14203 NY United States Veterans Administration Western New York Healthcare System Buffalo 14212 NY United States Department of Medicine Biomedical Genetics Boston University School of Medicine Boston 02118 MA United States Retina Service Massachusetts Eye & Ear Department of Ophthalmology Harvard Medical School Boston 02114 MA United States Genetics Genomics and Bioinformatics Graduate Program Jacobs School of Medicine and Biomedical Sciences State University of New York University at Buffalo Buffalo 14203 NY United States

Age-related macular degeneration (AMD) is a leading cause of blindness, affecting 200 million people worldwide. To identify genes that could be targeted for treatment, we created a molecular atlas at different stages of AMD. Our resource is comprised of RNA sequencing (RNA-seq) and DNA methylation microarrays from bulk macular retinal pigment epithelium (RPE)/choroid of clinically phenotyped normal and AMD donor eyes (n = 85), single-nucleus RNA-seq (164,399 cells), and single-nucleus assay for transposase-accessible chromatin (ATAC)-seq (125,822 cells) from the retina, RPE, and choroid of 6 AMD and 7 control donors. We identified 23 genome-wide significant loci differentially methylated in AMD, over 1,000 differentially expressed genes across different disease stages, and an AMD Müller state distinct from normal or gliosis. Chromatin accessibility peaks in genome-wide association study (GWAS) loci revealed putative causal genes for AMD, including HTRA1 and C6orf223. Our systems biology approach uncovered molecular mechanisms underlying AMD, including regulators of WNT signaling, FRZB and TLE2, as mechanistic players in disease. © 2023 The Authors

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Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil (vol 13, 1004, 2022)

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NATURE COMMUNICATIONS 2022年第1期13卷 1-11页

作者： Naslavsky, Michel S. Scliar, Marilia O. Yamamoto, Guilherme L. Wang, Jaqueline Yu Ting Zverinova, Stepanka Karp, Tatiana Nunes, Kelly Ceroni, Jose Ricardo Magliocco de Carvalho, Diego Lima da Silva Simoes, Carlos Eduardo Bozoklian, Daniel Nonaka, Ricardo dos Santos Brito Silva, Nayane da Silva Souza, Andreia de Souza Andrade, Heloisa Passos, Marilia Rodrigues Silva Castro, Camila Ferreira Bannwart Mendes-Junior, Celso T. Mercuri, Rafael L. V. Miller, Thiago L. A. Buzzo, Jose Leonel Rego, Fernanda O. Araujo, Nathalia M. Magalhaes, Wagner C. S. Mingroni-Netto, Regina Celia Borda, Victor Guio, Heinner Rojas, Carlos P. Sanchez, Cesar Caceres, Omar Dean, Michael Barreto, Mauricio L. Lima-Costa, Maria Fernanda Horta, Bernardo L. Tarazona-Santos, Eduardo Meyer, Diogo Galante, Pedro A. F. Guryev, Victor Castelli, Erick C. Duarte, Yeda A. O. Passos-Bueno, Maria Rita Zatz, Mayana Human Genome and Stem Cell Research Center University of São Paulo São Paulo SP Brazil Department of Genetics and Evolutionary Biology Biosciences Institute University of São Paulo São Paulo SP Brazil Hospital Israelita Albert Einstein São Paulo SP Brazil Instituto da Criança Faculdade de Medicina da Universidade de São Paulo São Paulo SP Brazil Orthopedic Research Labs Boston Children’s Hospital and Department of Genetics Harvard Medical School Boston MA USA Laboratório DASA São Paulo Brazil Laboratory of Genome Structure and Ageing European Research Institute for the Biology of Ageing University Medical Center Groningen Groningen Netherlands São Paulo State University (UNESP) Molecular Genetics and Bioinformatics Laboratory School of Medicine Botucatu State of São Paulo Brazil São Paulo State University (UNESP) Department of Pathology School of Medicine Botucatu State of São Paulo Brazil Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo Ribeirão Preto São Paulo Brazil Centro de Oncologia Molecular Hospital Sirio-Libanes São Paulo Brazil Department of Biochemistry Institute of Chemistry University of São Paulo São Paulo São Paulo Brazil Bioinformatics Graduate program University of São Paulo São Paulo Brazil Departamento de Genética Ecologia e Evolução Instituto de Ciências Biológicas Universidade Federal de Minas Gerais Belo Horizonte MG Brazil Núcleo de Ensino e Pesquisa Instituto Mário Penna Belo Horizonte MG Brazil Laboratorio de Biotecnologia y Biologia Molecular Instituto Nacional de Salud Lima Peru Universidad de Huánuco Huánuco Peru Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA Instituto de Saúde Coletiva Universidade Federal da Bahia Salvador BA 40110-040 Brazil Center for Data and Knowledge Integration for Health Institute Gonçalo Muniz Fundação Oswaldo Cruz Salvador BA Brazil Instituto de Pesquisas René Rachou Fundação Os

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.

关键词： Data publication and archiving Haplotypes Mobile elements Rare variants Structural variation

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Author Correction: A B-ARR-mediated cytokinin transcriptional network directs hormone cross-regulation and shoot development

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Nature communications 2018年第1期9卷 2075页

作者： Mingtang Xie Hongyu Chen Ling Huang Ryan C O'Neil Maxim N Shokhirev Joseph R Ecker Plant Biology Laboratory and Genomic Analysis Laboratory The Salk Institute for Biological Studies La Jolla CA 92037 USA. Howard Hughes Medical Institute The Salk Institute for Biological Studies La Jolla CA 92037 USA. Department of Computer Science Dartmouth College Hanover NH 03755 USA. The Razavi Newman Integrative Genomics and Bioinformatics Core Facility The Salk Institute for Biological Studies La Jolla CA 92037 USA. Bioinformatics Program University of California at San Diego La Jolla CA 92093 USA. Plant Biology Laboratory and Genomic Analysis Laboratory The Salk Institute for Biological Studies La Jolla CA 92037 USA. ecker@salk.edu. Howard Hughes Medical Institute The Salk Institute for Biological Studies La Jolla CA 92037 USA. ecker@salk.edu.

The original version of this Article contained an error in Fig. 3. Panel b was inadvertently duplicated and the correct panel c was originally omitted. This error has been corrected in both the PDF and HTML versions o...

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Proceedings of the 16th Annual UT-KBRIN bioinformatics Summit 2016: bioinformatics

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BMC bioinformatics 2017年第9期18卷 1-9页

作者： Eric C. Rouchka Juw Won Park Julia H. Chariker David A. Tieri Shreedharkumar Rajurkar Vikas Singh Nishchal K. Verma Yan Cui Mark Farman Bradford Condon Jolanta Jaromczyk Neil Moore Jerzy Jaromczyk Daniel Harris Patrick Calie Eun Kyong Shin Robert L. Davis Arash Shaban-Nejad Joshua M. Mitchell Hunter N. B. Moseley Robert M. Flight Qing Jun Wang Richard M. Higashi Teresa W-M Fan Andrew N. Lane Liangqun Lu Bernie J Daigle Jr. Xi Chen Andrey Smelter Jerzy W. Jaromczyk Bailey K. Phan Nathaniel J. Serpico Ethan G. Toney Li Chen Caroline E. Melton Jennifer R. Mandel Bernie J. Daigle Jr. Hao Chen Kazi I. Zaman Ramin Homayouni Patrick J. Trainor Andrew P. DeFilippis Samantha M. Carlisle Shesh N. Rai Department of Computer Engineering and Computer Science University of Louisville Duthie Center for Engineering Louisville KY 40292 USA Kentucky Biomedical Research Infrastructure (KBRIN) Bioinformatics Core 522 East Gray Street Louisville KY 40292 USA Department of Psychological and Brain Sciences University of Louisville Louisville KY 40292 USA Department of Anatomical Sciences and Neurobiology University of Louisville Louisville KY 40292 USA Department of Electrical Engineering IIT Kanpur India Department of Microbiology Immunology and Biochemistry University of Tennessee Health Science Center Memphis TN 38103 USA Center for Integrative and Translational Genomics University of Tennessee Health Science Center Memphis TN 38103 USA Department of Plant Pathology University of Kentucky Lexington KY 40546 USA UK Healthcare Genomics University of Kentucky Lexington KY 40536 USA Department of Entomology & Plant Pathology University of Tennessee Knoxville TN 37996 USA Department of Forestry University of Kentucky Lexington KY 40506 USA Department of Computer Science University of Kentucky Lexington KY 40506 USA Department of Computer Science University of Kentucky Lexington KY 40508 USA Department of Biological Sciences Eastern Kentucky University Richmond KY 40475 USA University of Tennessee Health Science Center – Oak-Ridge National Lab (UTHSC-ORNL) Center for Biomedical Informatics Department of Pediatrics Memphis TN 38103 USA Department of Molecular & Cellular Biochemistry University of Kentucky Lexington KY 40536 USA Markey Cancer Center University of Kentucky Lexington KY 40536 USA Center for Environmental and Systems Biochemistry University of Kentucky Lexington KY 40536 USA Institute for Biomedical Informatics University of Kentucky Lexington KY 40536 USA Department of Molecular and Cellular Biochemistry University of Kentucky Lexington KY 40536 USA Department of Statistics University of Kentucky Louisville KY

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An atlas of dynamic chromatin landscapes in mouse fetal development (vol 583, pg 744, 2020)

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NATURE 2021年第7842期589卷 E4-E4页

作者： Gorkin, David U. Barozzi, Iros Zhao, Yuan Zhang, Yanxiao Huang, Hui Lee, Ah Young Li, Bin Chiou, Joshua Wildberg, Andre Ding, Bo Zhang, Bo Wang, Mengchi Strattan, J. Seth Davidson, Jean M. Qiu, Yunjiang Afzal, Veena Akiyama, Jennifer A. Plajzer-Frick, Ingrid Novak, Catherine S. Kato, Momoe Garvin, Tyler H. Pham, Quan T. Harrington, Anne N. Mannion, Brandon J. Lee, Elizabeth A. Fukuda-Yuzawa, Yoko He, Yupeng Preissl, Sebastian Chee, Sora Han, Jee Yun Williams, Brian A. Trout, Diane Amrhein, Henry Yang, Hongbo Cherry, J. Michael Wang, Wei Gaulton, Kyle Ecker, Joseph R. Shen, Yin Dickel, Diane E. Visel, Axel Pennacchio, Len A. Ren, Bing Ludwig Institute for Cancer Research La Jolla CA USA Center for Epigenomics 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 School of Medicine La Jolla CA USA Department of Cellular and Molecular Medicine University of California San Diego School of Medicine La Jolla CA USA Institute of Genomic Medicine University of California San Diego School of Medicine La Jolla CA USA Moores Cancer Center University of California San Diego School of Medicine La Jolla CA USA Environmental Genomics and Systems Biology Division Lawrence Berkeley National Laboratory Berkeley CA USA Department of Surgery and Cancer Imperial College London London UK US Department of Energy Joint Genome Institute Berkeley CA USA School of Natural Sciences University of California Merced Merced CA USA Comparative Biochemistry Program University of California Berkeley Berkeley CA USA Genomic Analysis Laboratory Salk Institute for Biological Studies La Jolla CA USA Department of Pediatrics University of California San Diego School of Medicine La Jolla CA USA Department of Biochemistry and Molecular Biology Penn State School of Medicine Hershey PA USA Stanford University School of Medicine Department of Genetics Stanford CA USA Howard Hughes Medical Institute Salk Institute for Biological Studies La Jolla CA USA Division of Biology and Biological Engineering California Institute of Technology Pasadena CA USA Institute for Human Genetics and University of California San Francisco San Francisco CA USA Department of Neurology University of California San Francisco San Francisco CA USA

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Cancer Informatics: Profiling Age-Related Epigenetic Markers of Stomach Adenocarcinoma in Young and Old Subjects

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Cancer Informatics 2015年 14卷

作者： Byoung-Chul Kim Hyoung Oh Jeong Daeui Park Chul-Hong Kim Eun Kyeong Lee Dae Hyun Kim Eunok Im Nam Deuk Kim Sunghoon Lee Byung Pal Yu Jong Bhak Hae Young Chung Molecular Inflammation Research Center for Aging Intervention Pusan National University Busan Republic of Korea.Interdisciplinary Research Program of Bioinformatics and Longevity Science Pusan National University Busan Republic of Korea. Genomictree Inc. Yuseong-gu Daejeon Republic of Korea. Molecular Inflammation Research Center for Aging Intervention Pusan National University Busan Republic of Korea. Personal Genomics Institute Genome Research Foundation Suwon Republic of Korea.BioMedical Engineering UNIST Ulsan Republic of Korea. Department of Physiology University of Texas Health Science Center at San Antonio San Antonio TX USA.

The purpose of our study is to identify epigenetic markers that are differently expressed in the stomach adenocarcinoma (STAD) condition. Based on data from The Cancer Genome Atlas (TCGA), we were able to detect an age-related difference in methylation patterns and changes in gene and miRNA expression levels in young (n = 14) and old (n = 70) STAD subjects. Our analysis identified 323 upregulated and 653 downregulated genes in old STAD subjects. We also found 76 miRNAs with age-related expression patterns and 113 differentially methylated genes (DMGs), respectively. Our further analysis revealed that significant upregulated genes (n = 35) were assigned to the cell cycle, while the muscle system process (n = 27) and cell adhesion-related genes (n = 57) were downregulated. In addition, by comparing gene and miRNA expression with methylation change, we identified that three upregulated genes (ELF3, IL1β, and MMP13) known to be involved in inflammatory responses and cell growth were significantly hypomethylated in the promoter region. We further detected target candidates for age-related, downregulated miRNAs (hsa-mir-124-3, hsa-mir-204, and hsa-mir-125b-2) in old STAD subjects. This is the first report of the results from a study exploring age-related epigenetic biomarkers of STAD using high-throughput data and provides evidence for a complex clinicopathological condition expressed by the age-related STAD progression.

关键词： stomach adenocarcinoma age TCGA RNAseq miRNA DNA methylation

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Author Correction: A B-ARR-mediated cytokinin transcriptional network directs hormone cross-regulation and shoot development

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Nature communications 2023年第1期14卷 5988页

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Author Correction: Whole genome sequencing reveals the impact of recent artificial selection on red sea bream reared in fish farms

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Scientific reports 2020年第1期10卷 1625页

作者： Bo-Hye Nam DongAhn Yoo Young-Ok Kim Jung Youn Park Younhee Shin Ga-Hee Shin Chan-Il Park Heebal Kim Woori Kwak Biotechnology Research Division National Institute of Fisheries Science Busan 46083 Republic of Korea. Interdisciplinary Program in Bioinformatics Seoul National University Seoul Republic of Korea. Research and Development Center Insilicogen Inc. Gyeonggi-do 16954 Republic of Korea. Department of Marine Biology & Aquaculture Gyeongsang National University Tongyeong 53064 Republic of Korea. C&K genomics 26 Beobwon-ro 9-gil H business Park Bldg. C #1008 Songpa-gu Seoul Republic of Korea. Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences 7 Seoul National University Seoul Republic of Korea. C&K genomics 26 Beobwon-ro 9-gil H business Park Bldg. C #1008 Songpa-gu Seoul Republic of Korea. asleo@***.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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