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IEEE International Conference on bioinformatics and Biomedicine

作者： Hyung Sun Kim Changwoo Yi Yongkang Kim Uhnmee Park Woong Kook Hyuk Kim Taesung Park Interdisciplinary Program in bioinformatics Seoul National University The Research Institute of Basic Sciences College of Natural Sciences Seoul National University Department of Statistics Seoul National University Department of Bioscience and biotechnology University of Suwon Department of Mathematical Sciences and Institute for Mathematical Data Analytics Research Center Seoul National University Department of Mathematical Sciences Seoul National University

ISBN: (纸本)9781538654897;9781538654880

Type 2 diabetes (T2D) is now a rapidly increasing, worldwide scourge, and the identification of genetic contributors is vital. However, current analyses of multiple, disease-contributing factors, and their combined interactions, remains quite difficult, using traditional approaches. Topological data analysis (TDA) shows what shape a data set can have, facilitating clustering analysis, by determining which components are close to each other. Thus, TDA can generate a network, using single-nucleotide polymorphism (SNP) data, revealing the genetic relatedness of specific individuals, and can derive multiple ordered subgroups, from one with a low patient concentration, to one with a high patient concentration. Since it is widely accepted that T2D pathogenesis is affected by multiple genetic factors, we performed TDA on T2D data from the Korea Association REsource (KARE) project, a population-based, genome-wide association study of the Korean adult population. Since KARE data contains follow-up information about the incidence of T2D, we compared the T2D status of each individual, at baseline, with that of 10 years later. For the TDA network-driven subgroups, ordered by prevalence, we compared the T2D incidence rate, after 10 years, for individuals initially without T2D. As a result, we found that the TDA network-driven, ordered subgroups had significantly increased incidence rates, linearly correlated with prevalence (p-value = 0.006914). Our results demonstrate the usefulness of TDA in both identifying genetic contributors (e.g., SNPs), and their interrelationships, in the pathology of complex diseases.

关键词： Data analysis Genetics bioinformatics Diabetes Diseases Conferences Data mining

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Gene knockout inference with variational graph autoencoder learning single-cell gene regulatory networks

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Nucleic acids research 2023年第13期51卷 6578-6592页

作者： Yongjian Yang Guanxun Li Yan Zhong Qian Xu Bo-Jia Chen Yu-Te Lin Robert S Chapkin James J Cai Department of Electrical and Computer Engineering Texas A&M University College Station TX 77843 USA. Department of Statistics Texas A&M University College Station TX 77843 USA. Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of Statistics East China Normal University 3663 North Zhongshan Road Shanghai 200062 China. Department of Veterinary Integrative Biosciences Texas A&M University College Station TX 77843 USA. Graduate Institute of Microbiology and Public Health College of Veterinary Medicine National Chung Hsing University Taichung 402 Taiwan. Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan. Program in Integrative & Complex Diseases Department of Nutrition Texas A&M University College Station TX 77843 USA. Interdisciplinary Program of Genetics Texas A&M University College Station TX 77843 USA.

In this paper, we introduce Gene Knockout Inference (GenKI), a virtual knockout (KO) tool for gene function prediction using single-cell RNA sequencing (scRNA-seq) data in the absence of KO samples when only wild-type (WT) samples are available. Without using any information from real KO samples, GenKI is designed to capture shifting patterns in gene regulation caused by the KO perturbation in an unsupervised manner and provide a robust and scalable framework for gene function studies. To achieve this goal, GenKI adapts a variational graph autoencoder (VGAE) model to learn latent representations of genes and interactions between genes from the input WT scRNA-seq data and a derived single-cell gene regulatory network (scGRN). The virtual KO data is then generated by computationally removing all edges of the KO gene-the gene to be knocked out for functional study-from the scGRN. The differences between WT and virtual KO data are discerned by using their corresponding latent parameters derived from the trained VGAE model. Our simulations show that GenKI accurately approximates the perturbation profiles upon gene KO and outperforms the state-of-the-art under a series of evaluation conditions. Using publicly available scRNA-seq data sets, we demonstrate that GenKI recapitulates discoveries of real-animal KO experiments and accurately predicts cell type-specific functions of KO genes. Thus, GenKI provides an in-silico alternative to KO experiments that may partially replace the need for genetically modified animals or other genetically perturbed systems.

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Erratum to: DNA methylation and transcriptional noise

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Epigenetics & Chromatin 2014年第1期7卷 1-1页

作者： Iksoo Huh Taesung Park Jia Zeng Soojin V Yi Department of Statistics Bioinformatics and Biostatistics Laboratory Interdisciplinary Program in Bioinformatics Seoul National University Seoul 151-742 South Korea School of Biology Institute of Bioengineering and Biosciences Georgia Institute of Technology 310 Ferst Drive Atlanta GA 30332 USA

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Comparative analysis of different approaches for dealing with candidate regions in the context of a genome-wide association study

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BMC proceedings 2009年第7-Sup期3 Suppl 7卷 S93页

作者： Francesca Lantieri Min A Jhun Jungsun Park Taesung Park Marcella Devoto The Children's Hospital of Philadelphia 3615 Civic Center Boulevard Philadelphia Pennsylvania 19104 USA. Dipartimento di Scienze della Salute sezione di Biostatistica Universita' degli Studi di Genova via Pastore 1 16132 Genoa Italy. Interdisciplinary Program in Bioinformatics Seoul National University Seoul 56-1 Shillim-Dong Kwanak-Gu Seoul 151-742 Korea. Department of Statistics Seoul National University Seoul 56-1 Shillim-Dong Kwanak-Gu 151-747 Korea. Department of Pediatrics and CCEB University of Pennsylvania 3615 Civic Center Boulevard Philadelphia Pennsylvania 19104 USA. Dipartimento di Medicina Sperimentale Universita' La Sapienza Viale Regina Elena 324 00161 Roma Italy.

Genome-wide association studies (GWAS) test hundreds of thousands of single-nucleotide polymorphisms (SNPs) for association to a trait, treating each marker equally and ignoring prior evidence of association to specific regions. Typically, promising regions are selected for further investigation based on p-values obtained from simple tests of association. However, loci that exert only a weak, low-penetrant role on the trait, producing modest evidence of association, are not detectable in the context of a GWAS. Implementing prior knowledge of association in GWAS could increase power, help distinguish between false and true positives, and identify better sets of SNPs for follow-up *** we performed a GWAS on rheumatoid arthritis (RA) patients and controls (Problem 1, Genetic Analysis Workshop 16). In order to include prior information in the analysis, we applied four methods that distinctively deal with markers in candidate genes in the context of GWAS. SNPs were divided into a random and a candidate subset, then we applied empirical correction by permutation, false-discovery rate, false-positive report probability, and posterior odds of association using different prior probabilities. We repeated the same analyses on two different sets of candidate markers defined on the basis of previously reported association to RA following two different approaches. The four methods showed similar relative behavior when applied to the two sets, with the proportion of candidate SNPs ranked among the top 2,000 varying from 0 to 100%. The use of different prior probabilities changed the stringency of the methods, but not their relative performance.

关键词： Rheumatoid Arthritis Prior Probability Candidate Marker Candidate SNPs Genetic Analysis Workshop

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Erratum to: Integrative analysis of multi-omics data for identifying multi-markers for diagnosing pancreatic cancer

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BMC genomics 2017年第1期18卷 88页

作者： Min-Seok Kwon Yongkang Kim Seungyeoun Lee Junghyun Namkung Taegyun Yun Sung Gon Yi Sangjo Han Meejoo Kang Sun Whe Kim Jin-Young Jang Taesung Park Interdisciplinary program in Bioinformatics Seoul National University Seoul Korea. Department of Statistics Seoul National University Seoul Korea. Department of Mathematics and Statistics Sejong University Seoul Korea. Immunodiagnostics R&D Team IVD Business Unit New Business Division SK telecom Co Seongnam Korea. Department of Surgery Seoul National University Hospital Seoul Korea. Department of Surgery Seoul National University Hospital Seoul Korea. jangjy4@***. Interdisciplinary program in Bioinformatics Seoul National University Seoul Korea. tspark@stats.snu.ac.kr. Department of Statistics Seoul National University Seoul Korea. tspark@stats.snu.ac.kr.

A correction to the article 'Integrative Analysis of Multiomics Data for Identifying Multi-Markers for Diagnosing Pancreatic Cancer,' published in a previous issue is prpresented

关键词： PANCREATIC cancer TUMOR markers

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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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scTenifoldXct: A semi-supervised method for predicting cell-cell interactions and mapping cellular communication graphs

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Cell systems 2023年第4期14卷 302-311.e4页

作者： Yongjian Yang Guanxun Li Yan Zhong Qian Xu Yu-Te Lin Cristhian Roman-Vicharra Robert S Chapkin James J Cai Department of Electrical and Computer Engineering Texas A&M University College Station TX 77843 USA. Department of Statistics Texas A&M University College Station TX 77843 USA. Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of Statistics East China Normal University 3663 North Zhongshan Road Shanghai 200062 China. Department of Veterinary Integrative Biosciences Texas A&M University College Station TX 77843 USA. Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan. Department of Nutrition and the Program in Integrative Nutrition & Complex Diseases Texas A&M University College Station TX 77843 USA. Electronic address: r-chapkin@tamu.edu. Department of Electrical and Computer Engineering Texas A&M University College Station TX 77843 USA Department of Veterinary Integrative Biosciences Texas A&M University College Station TX 77843 USA Interdisciplinary Program of Genetics Texas A&M University College Station TX 77843 USA. Electronic address: jcai@tamu.edu.

We present scTenifoldXct, a semi-supervised computational tool for detecting ligand-receptor (LR)-mediated cell-cell interactions and mapping cellular communication graphs. Our method is based on manifold alignment, using LR pairs as inter-data correspondences to embed ligand and receptor genes expressed in interacting cells into a unified latent space. Neural networks are employed to minimize the distance between corresponding genes while preserving the structure of gene regression networks. We apply scTenifoldXct to real datasets for testing and demonstrate that our method detects interactions with high consistency compared with other methods. More importantly, scTenifoldXct uncovers weak but biologically relevant interactions overlooked by other methods. We also demonstrate how scTenifoldXct can be used to compare different samples, such as healthy vs. diseased and wild type vs. knockout, to identify differential interactions, thereby revealing functional implications associated with changes in cellular communication status.

关键词： cell-cell interaction cellular communication gene regression network machine learning manifold alignment neural networks scRNA-seq single-cell RNA sequencing

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Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers Abstracts

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FLUIDS AND BARRIERS OF THE CNS 2017年第Sup2期14卷 1-23页

作者： [Anonymous] 1. The Jerzy Kukuczka Academy of Physical Education Katowice Poland 2. The Institute of Animal Physiology and Food Research Polish Academy of Sciences Olsztyn Poland 3. University of Miami Miami FL USA 4. Institute of Pharmaceutical Science King’s College London London United Kingdom 5. Department of Ophthalmology and Molecular and Integrative Physiology The University of Michigan Ann Arbor MI USA 6. Department of Internal Medicine and Cardiology The University of Michigan Ann Arbor MI USA 129. Department of Cellular and Molecular Medicine Medical Faculty Koc University Istanbul Turkey 7. School of Medicine Department of Cellular and Molecular Medicine Koc University Istanbul Turkey 130. Department of Neuroscience Medical Faculty Koc University Istanbul Turkey 8. Department of Neuroscience School of Medicine Koc University Istanbul Turkey 9. Department of Laboratory Animals Science Aziz Sancar Experimental Medicine Research Institute Istanbul University Istanbul Turkey 10. Department of Neuroscience Aziz Sancar Experimental Medicine Research Institute Istanbul University Istanbul Turkey 11. School of Medicine Koc University Istanbul Turkey 12. Department of Forensic Science Istanbul Faculty of Medicine Istanbul University Istanbul Turkey 13. Department of Histology and Embryology School of Medicine Koc University Istanbul Turkey 14. Department of Histology and Embryology Istanbul Faculty of Medicine Istanbul University Istanbul Turkey 15. Department of Physiology School of Medicine Koc University Istanbul Turkey 16. Theodor Kocher Institute University of Bern Bern Switzerland 17. Institute of Veterinary Physiology Vetsuisse Faculty University of Zurich Zurich Switzerland 18. Zurich Center for Integrative Human Physiology University of Zurich Zurich Switzerland 121. Zurich Center of Integrative Human Physiology University of Zurich Zurich Switzerland 55. Institute for Veterinary Physiology and Zurich Center for Integrative Human Physiology

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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)

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NATURE GENETICS 2018年第12期50卷 1755-1755页

作者： Evangelou, Evangelos Warren, Helen R. Mosen-Ansorena, David Mifsud, Borbala Pazoki, Raha Gao, He Ntritsos, Georgios Dimou, Niki Cabrera, Claudia P. Karaman, Ibrahim Fu Liang Ng Evangelou, Marina Witkowska, Katarzyna Tzanis, Evan Hellwege, Jacklyn N. Giri, Ayush Edwards, Digna R. Velez Sun, Yan V. Cho, Kelly Gaziano, J. Michael Wilson, Peter W. F. Tsao, Philip S. Kovesdy, Csaba P. Esko, Tonu Magi, Reedik Milani, Lili Almgren, Peter Boutin, Thibaud Debette, Stephanie Ding, Jun Giulianini, Franco Holliday, Elizabeth G. Jackson, Anne U. Li-Gao, Ruifang Lin, Wei-Yu Luan, Jian'an Mangino, Massimo Oldmeadow, Christopher Prins, Bram Peter Qian, Yong Sargurupremraj, Muralidharan Shah, Nabi Surendran, Praveen Theriault, Sebastien Verweij, Niek Willems, Sara M. Zhao, Jing-Hua Amouyel, Philippe Connell, John de Mutsert, Renee Doney, Alex S. F. Farrall, Martin Menni, Cristina Morris, Andrew D. Noordam, Raymond Pare, Guillaume Poulter, Neil R. Shields, Denis C. Stanton, Alice Thom, Simon Abecasis, Goncalo Amin, Najaf Arking, Dan E. Ayers, Kristin L. Barbieri, Caterina M. Batini, Chiara Bis, Joshua C. Blake, Tineka Bochud, Murielle Boehnke, Michael Boerwinkle, Eric Boomsma, Dorret I. Bottinger, Erwin P. Braund, Peter S. Brumat, Marco Campbell, Archie Campbell, Harry Chakravarti, Aravinda Chambers, John C. Chauhan, Ganesh Ciullo, Marina Cocca, Massimiliano Collins, Francis Cordell, Heather J. Davies, Gail de Borst, Martin H. de Geus, Eco J. Deary, Ian J. Deelen, Joris Del Greco, Fabiola M. Demirkale, Cumhur Yusuf Dorr, Marcus Ehret, Georg B. Elosua, Roberto Enroth, Stefan Erzurumluoglu, A. Mesut Ferreira, Teresa Franberg, Mattias Franco, Oscar H. Gandin, Ilaria Gasparini, Paolo Giedraitis, Vilmantas Gieger, Christian Girotto, Giorgia Goel, Anuj Gow, Alan J. Gudnason, Vilmundur Guo, Xiuqing Gyllensten, Ulf Hamsten, Anders Harris, Tamara B. Harris, Sarah E. Hartman, Catharina A. Havulinna, Aki S. Hicks, Andrew A. Hofer, Edith Hofman, Albert Hottenga, Jouke-Jan Huffman, Jennifer E. Hwang, Shih-Jen Ingelsson, Erik James, Alan Jansen Department of Epidemiology and Biostatistics Imperial College London London UK Department of Hygiene and Epidemiology University of Ioannina Medical School Ioannina Greece William Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London London UK National Institute for Health Research Barts Cardiovascular Biomedical Research Center Queen Mary University of London London UK MRC-PHE Centre for Environment and Health Imperial College London London UK Department of Mathematics Imperial College London London UK Division of Epidemiology Department of Medicine Institute for Medicine and Public Health Vanderbilt Genetics Institute Vanderbilt University Medical Center Tennessee Valley Healthcare System (626)/Vanderbilt University Nashville TN USA Vanderbilt Genetics Institute Vanderbilt Epidemiology Center Department of Obstetrics and Gynecology Vanderbilt University Medical Center Tennessee Valley Health Systems VA Nashville TN USA Department of Epidemiology Emory University Rollins School of Public Health Atlanta GA USA Department of Biomedical Informatics Emory University School of Medicine Atlanta GA USA Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) VA Boston Healthcare System Boston MA USA Division of Aging Department of Medicine Brigham and Women’s Hospital Department of Medicine Harvard Medical School Boston MA USA Atlanta VAMC and Emory Clinical Cardiovascular Research Institute Atlanta GA USA VA Palo Alto Health Care System Division of Cardiovascular Medicine Stanford University School of Medicine Stanford CA USA Nephrology Section Memphis VA Medical Center and University of Tennessee Health Science Center Memphis TN USA Estonian Genome Center University of Tartu Tartu Estonia Program in Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA Department Clinical Sciences Malmö Lund University Malmö Sweden MRC Human Genetics Un

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

关键词： Cardiovascular diseases Genome informatics Genome-wide association studies

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Patterns of somatic structural variation in human cancer genomes (vol 578, pg 112, 2020)

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NATURE 2023年第7948期614卷 E38-E38页

作者： Li, Yilong Roberts, Nicola D. Wala, Jeremiah A. Shapira, Ofer Schumacher, Steven E. Kumar, Kiran Khurana, Ekta Waszak, Sebastian Korbel, Jan O. Haber, James E. Imielinski, Marcin Weischenfeldt, Joachim Beroukhim, Rameen Campbell, Peter J. Cancer Genome Project Wellcome Trust Sanger Institute Hinxton UK Totient Inc Cambridge MA USA Wellcome Sanger Institute Wellcome Genome Campus Hinxton UK Department of Haematology University of Cambridge Cambridge UK Cambridge University Hospitals NHS Foundation Trust Cambridge UK Korea Advanced Institute of Science and Technology Daejeon South Korea Department of Zoology Genetics and Physical Anthropology University of Santiago de Compostela Santiago de Compostela Spain Centre for Research in Molecular Medicine and Chronic Diseases (CIMUS) University of Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) University of Vigo Vigo Spain Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain Department of Zoology Genetics and Physical Anthropology (CiMUS) Universidade de Santiago de Compostela Santiago de Compostela Spain The Biomedical Research Centre (CINBIO) Universidade de Vigo Vigo Spain The Broad Institute of Harvard and MIT Cambridge MA USA Bioinformatics and Integrative Genomics Harvard University Cambridge MA USA Department of Cancer Biology Dana-Farber Cancer Institute Boston MA USA Broad Institute of MIT and Harvard Cambridge MA USA Department of Medical Oncology Dana-Farber Cancer Institute Boston MA USA Harvard Medical School Boston MA USA Massachusetts General Hospital Center for Cancer Research Charlestown MA USA Dana-Farber Cancer Institute Boston MA USA Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard Medical School Boston MA USA Weill Cornell Medical College New York NY USA Department of Physiology and Biophysics Weill Cornell Medicine New York NY USA Institute for Computational Biomedicine Weill Cornell Medicine New York NY USA Controlled Department and Institution New York NY USA Englander Institute for Precision Medicine Weill Cornell Medicine Ne

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