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21 results on '"Eileen Png"'

1. Life stage impact on the human skin ecosystem: lipids and the microbial community

Author

Martin P. Pagac, Bala Davient, Luca Antonio Plado, Hilbert Yuen In Lam, Shi Mun Lee, Aarthi Ravikrishnan, Wee Ling Esther Chua, Sneha Muralidharan, Aishwarya Sridharan, Antony S. Irudayaswamy, Ramasamy Srinivas, Stephen Wearne, Ahmad Nazri Mohamed Naim, Eliza Xin Pei Ho, H. Q. Amanda Ng, Junmei Samantha Kwah, Eileen Png, Anne K. Bendt, Markus R. Wenk, Federico Torta, Niranjan Nagarajan, John Common, Yap Seng Chong, Elizabeth Huiwen Tham, Lynette Pei-Chi Shek, Evelyn Xiu Ling Loo, John Chambers, Yik Weng Yew, Marie Loh, and Thomas L. Dawson

Subjects
Microbial ecology, QR100-130
Abstract

Abstract Sebaceous free fatty acids are metabolized by multiple skin microbes into bioactive lipid mediators termed oxylipins. This study investigated correlations between skin oxylipins and microbes on the superficial skin of pre-pubescent children (N = 36) and adults (N = 100), including pre- (N = 25) and post-menopausal females (N = 25). Lipidomics and metagenomics revealed that Malassezia restricta positively correlated with the oxylipin 9,10-DiHOME on adult skin and negatively correlated with its precursor, 9,10-EpOME, on pre-pubescent skin. Co-culturing Malassezia with keratinocytes demonstrated a link between 9,10-DiHOME and pro-inflammatory cytokines IL-1β and IL-6 production. We also observed strong correlations between other skin oxylipins and microbial taxa, highlighting life stage differences in sebum production and microbial community composition. Our findings imply a complex host-microbe communication system mediated by lipid metabolism occurring on human skin, warranting further research into its role in skin health and disease and paving the way towards novel therapeutic targets and treatments.

Published
2025
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2. Gut metagenomes of Asian octogenarians reveal metabolic potential expansion and distinct microbial species associated with aging phenotypes

Author

Aarthi Ravikrishnan, Indrik Wijaya, Eileen Png, Kern Rei Chng, Eliza Xin Pei Ho, Amanda Hui Qi Ng, Ahmad Nazri Mohamed Naim, Jean-Sebastien Gounot, Shou Ping Guan, Jasinda Lee Hanqing, Lihuan Guan, Chenhao Li, Jia Yu Koh, Paola Florez de Sessions, Woon-Puay Koh, Lei Feng, Tze Pin Ng, Anis Larbi, Andrea B. Maier, Brian K. Kennedy, and Niranjan Nagarajan

Subjects
Science
Abstract

Abstract While rapid demographic changes in Asia are driving the incidence of chronic aging-related diseases, the limited availability of high-quality in vivo data hampers our ability to understand complex multi-factorial contributions, including gut microbial, to healthy aging. Leveraging a well-phenotyped cohort of community-living octogenarians in Singapore, we used deep shotgun-metagenomic sequencing for high-resolution taxonomic and functional characterization of their gut microbiomes (n = 234). Joint species-level analysis with other Asian cohorts identified distinct age-associated shifts characterized by reduction in microbial richness, and specific Alistipes and Bacteroides species enrichment (e.g., Alistipes shahii and Bacteroides xylanisolvens). Functional analysis confirmed these changes correspond to metabolic potential expansion in aging towards alternate pathways synthesizing and utilizing amino-acid precursors, vis-à-vis dominant microbial guilds producing butyrate in gut from pyruvate (e.g., Faecalibacterium prausnitzii, Roseburia inulinivorans). Extending these observations to key clinical markers helped identify >10 robust microbial associations to inflammation, cardiometabolic and liver health, including potential probiotic species (e.g., Parabacteroides goldsteinii) and pathobionts (e.g., Klebsiella pneumoniae), highlighting the microbiome’s role as biomarkers and potential targets for promoting healthy aging.

Published
2024
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3. Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn’s disease

Author

Shijia Hu, Eileen Png, Michelle Gowans, David E. H. Ong, Paola Florez de Sessions, Jie Song, and Niranjan Nagarajan

Subjects
Crohn’s disease, Gastrointestinal microbiome, Oral microbiome, Metagenomics, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background This study aims to characterize, the gut and oral microbiome in Asian subjects with Crohn’s disease (CD) using whole genome shotgun sequencing, thereby allowing for strain-level comparison. Methods A case–control study with age, sex and ethnicity matched healthy controls was conducted. CD subjects were limited to well-controlled patients without oral manifestations. Fecal and saliva samples were collected for characterization of gut and oral microbiome respectively. Microbial DNA were extracted, libraries prepared and sequenced reads profiled. Taxonomic diversity, taxonomic association, strain typing and microbial gene pathway analyses were conducted. Results The study recruited 25 subjects with CD and 25 healthy controls. The oral microbe Streptococcus salivarius was found to be enriched and of concordant strains in the gut and oral microbiome of Crohn’s disease subjects. This was more likely in CD subjects with higher Crohn’s Disease Activity Index (184.3 ± 2.9 vs 67.1 ± 82.5, p = 0.012) and active disease status (Diarrhoea/abdominal pain/blood-in-stool/fever and fatigue) (p = 0.016). Gut species found to be significantly depleted in CD compared to control (Relative abundance: Median[Range]) include: Faecalibacterium prausnitzii (0.03[0.00–4.56] vs 13.69[5.32–18.71], p = 0.010), Roseburia inulinivorans (0.00[0.00–0.03] vs 0.21[0.01–0.53], p = 0.010) and Alistipes senegalensis (0.00[0.00–0.00] vs 0.00[0.00–0.02], p = 0.029). While Clostridium nexile (0.00[0.00–0.12] vs 0.00[0.00–0.00], p = 0.038) and Ruminococcus gnavus (0.43[0.02–0.33] vs 0.00[0.00–0.13], p = 0.043) were found to be enriched. C. nexile enrichment was not found in CD subjects of European descent. Microbial arginine (Linear-discriminant-analysis: 3.162, p = 0.001) and isoprene (Linear-discriminant-analysis: 3.058, p

Published
2021
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4. Common Genetic Variations Associated with the Persistence of Immunity following Childhood Immunization

Author

Daniel O’Connor, Eileen Png, Chiea Chuen Khor, Matthew D. Snape, Adrian V.S. Hill, Fiona van der Klis, Clive Hoggart, Michael Levin, Martin L. Hibberd, and Andrew J. Pollard

Subjects
Biology (General), QH301-705.5
Abstract

Summary: Vaccines have revolutionized public health, preventing millions of deaths each year, particularly in childhood. Yet, there is considerable variability in the magnitude and persistence of vaccine-induced immunity. Maintenance of specific antibody is essential for continuity of vaccine-induced serological protection. We conducted a genome-wide association study into the persistence of immunity to three childhood vaccines: capsular group C meningococcal (MenC), Haemophilus influenzae type b, and tetanus toxoid (TT) vaccines. We detail associations between variants in a locus containing a family of signal-regulatory proteins and the persistence MenC immunity. We postulate a regulatory role for the lead SNP, with supporting epigenetic and expression quantitative trait loci data. Furthermore, we define associations between SNPs in the human leukocyte antigen (HLA) locus and the persistence of TT-specific immunity. Moreover, we describe four classical HLA alleles, HLA DRB1∗0301, HLA DQB1∗0201, HLA DQB1∗0602, and HLA DRB1∗1501, associated with TT-specific immunity, independent of the lead SNP association. : Genetic variants impact immune responses to antigenic stimuli. O’Connor et al. show that variants within the human leukocyte antigen (HLA) and signal-regulatory proteins loci are associated with persistence of immunity following immunization, suggesting these genes are involved in regulating immune responses to routine childhood immunization. Keywords: vaccine-induced immunity, GWAS, persistence of immunity, meningococcal disease, HLA, SIRPG

Published
2019
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5. Extensive Ethnic Variation and Linkage Disequilibrium at the FCGR2/3 Locus: Different Genetic Associations Revealed in Kawasaki Disease

Author

Sietse Q. Nagelkerke, Carline E. Tacke, Willemijn B. Breunis, Michael W. T. Tanck, Judy Geissler, Eileen Png, Long T. Hoang, Joris van der Heijden, Ahmad N. M. Naim, Rae S. M. Yeung, Michael L. Levin, Victoria J. Wright, David P. Burgner, Anne-Louise Ponsonby, Justine A. Ellis, Rolando Cimaz, Chisato Shimizu, Jane C. Burns, Karin Fijnvandraat, C. Ellen van der Schoot, Timo K. van den Berg, Martin de Boer, Sonia Davila, Martin L. Hibberd, Taco W. Kuijpers, The International Kawasaki Disease Genetics Consortium, Nagib Dahdah, and Isabelle Kone-Paut

Subjects
Fc-gamma receptor, FCGR polymorphism, linkage disequilibrium, Kawasaki disease (KD), immunogenetics, Immunologic diseases. Allergy, RC581-607
Abstract

The human Fc-gamma receptors (FcγRs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All human low-affinity FcγRs are encoded by the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) and gene copy number variants. This locus is notoriously difficult to genotype and high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at the FCGR2/3 locus in >4,000 individuals to define linkage disequilibrium (LD) and allele frequencies in different populations. Strong LD and extensive ethnic variation in allele frequencies was found across the locus. LD was strongest for the FCGR2C-ORF haplotype (rs759550223+rs76277413), which leads to expression of FcγRIIc. In Europeans, the FCGR2C-ORF haplotype showed strong LD with, among others, rs201218628 (FCGR2A-Q27W, r2 = 0.63). LD between these two variants was weaker (r2 = 0.17) in Africans, whereas the FCGR2C-ORF haplotype was nearly absent in Asians (minor allele frequency

Published
2019
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7. A global metagenomic map of urban microbiomes and antimicrobial resistance

Author

Nadine Farhat, Tomoki Takeda, Astred Castro, Ken McGrath, Khaliun Sanchir, Iman Hajirasouliha, Eunice So, Laraib Zafar, Diana N. Nunes, Harun Mustafa, Amy Zhang, Priscilla Lisboa, Christian Schori, Marisano James, Jasna Chalangal, Sebastien Halary, Shahryar Rana, Yunmi Lee, Oli Schacher, Liliana Godoy, David A. Coil, Phanthira Pugdeethosal, Michelle D. Williams, German Marchandon, Angela Cantillo, Naoya Takahashi, Christopher Mozsary, Juana Gonzalez, Patrick K. H. Lee, Gerardo de Lamotte, Alessandro Robertiello, Steven Du, Fabienne Velter, Stefan G. Stark, Miguel Carbajo, Vincent Matthys, David A. Westfall, Julia Boeri, Irène Mauricette Mendy, Jonathan Cedillo, Francesco Oteri, Robert W. Crawford, Takayuki Ito, Tina Wunderlin, Maureen Muscat, David Paez-Espino, Carmen Urgiles, Aida Nesimi, Steffen Schaaf, Adan Ramirez-Rojas, Kunihiko Miyake, Christopher E. Mason, Anais Cardenas, Sharah Islam, Diego Benítez, Melissa Pool Pizzi, Kianna Ciaramella, Ciro Borrelli, Riham Islam, Dorottya Nagy-Szakal, Abd-Manaaf Bakere, Ait-hamlat Adel, Olha Lakhneko, Badamnyambuu Iderzorig, Ana Valeria Castro, Adam Phillips, Robert A. Petit, Flavia Corsi, Romain Conte, Krista Ryon, Soojin Jang, Joseph Benson, Fernanda de Souza Gomes Kehdy, Cindy Wang, Nicole Mathews, Jenn-Wei Chen, Rachel Paras, Paulina Pastuszek, Abigail Lyons, Paul Roldán, Muntaha Munia, Pierre Nicolas, Cassie L. Ettinger, Kyrylo Pyrshev, Katterinne N. Mendez, Eduardo Castro-Nallar, Valeriia Dotsenko, Michelle Tuz, Krizzy Mallari, Eileen Png, Yuya Sonohara, Tanja Miketic, Stéphane Delmas, Shu Zhang, Masaki Sato, Yuanting Zheng, Jifeng Zhu, Roland Häusler, Lucie Bittner, Savlatjon Rahmatulloev, Jonathan Foox, Bruno D'Alessandro, Alketa Plaku, Faisal Alquaddoomi, Yang Zhang, Kern Rei Chng, Juliana Lago, Allaeddine Chettouh, Tamera Henry, Houtan Noushmehr, Tranette Gregory, Sara Abdul Majid, Frank J. Kelly, Benjamin Pulatov, Laurie Casalot, Takema Kajita, Lennard Epping, Thais Fernanda Bartelli, Eftar Moniruzzaman, Renee Vivancos-Koopman, Thirumalaisamy P. Velavan, Tracy W. Liu, Yelyzaveta Tymoshenko, Alma Plaku, Nika Gurianova, Ambar Mendez, Anna Tomaselli, Sonia Dorado, Donato Giovannelli, Hira Choudhry, Synti Ng, Sheelta S. Kumar, Jennifer Q. Lu, Weijun Liang, Ellen Koag, Dennis Gankin, Maria João Amorim, Gwenola Simon, Kiyoshi Suganuma, Mikhail Karasikov, Christos A. Ouzounis, Madelyn May, Eran Elhaik, Stephan Ossowski, Kevin Bolzli, Matthew Arthur, Yuya Oto, Jananan Pathmanathan, Salah Mahmoud, Kou Takahashi, Brunna Marques, Kelly French, Felipe Sepúlveda, Shusei Yoshikawa, Paulo Thiago de Souza Santos, Andrew N. Gray, Juliana S Bernardes, Felipe Segato, Björn Brindefalk, George C. Yeh, Jhovana L. Velasco Flores, Jill Sullivan, Silva Baburyan, Denisse Flores, Russell Y. Neches, Sabrina Persaud, Rasheena Wright, Takumi Togashi, Verónica Antelo, Nao Kato, Skye Felice, Tatjana Mustac, Daisy Donnellan, Katerine Carrillo, Anna Litskevitch, Catalina García, Sota Ito, Naya Eady, Andrew Wan, Irene Meng, Sophie Guasco, Danilo Ercolini, Francesca De Filippis, Vincent Lemaire, Luice Fan, Lothar H. Wieler, Mariia Rybak, Jorge Sanchez, Jonathan S. Gootenberg, Itsuki Tomita, Maritza S Mosella, Laura Garcia, Natalka Makogon, Daisy Cheung, Hitler Francois Vasquez Arevalo, Freddy Asenjo, Gabriela P. Branco, Erika Cifuentes, Chloé Dequeker, Aspassia D. Chatziefthimiou, Alexis Terrero, Roy Meoded, Isabelle de Oliveira Moraes, Shaleni K. Singh, Orgil-Erdene Molomjamts, Karishma Miah, Laurent David, Wolfgang Haehr, Dao Phuong Giang, Romain Lannes, Prashanthi Ratnanandan, Ryota Yamanaka, Riccardo Vicedomini, Sadaf Ayaz, Oluwatosin M. Osuolale, Laura E. Vann, Gregory Chem, Andrea Gonzalez, Aszia Burrell, Ariel Chernomoretz, Sakura Ishizuka, Michelle Rivera, Avigdor Nosrati, Michelle B. Chen, Juliette Auvinet, Nils Ordioni, Tomoro Warashina, Guillaume Blanc, Tomislav Ivankovic, Christina Black, Lauren E. Hittle, David Hess-Homeier, Michael Kozhar, Hamood Suliman, Karobi Moitra, Saher Rahiel, Spyridon Gkotzis, Jenny Arevalo, Shaikh B. Iqbal, Beth Mutai, Mohammed Mohsin, Scott Tighe, Sylvie Collin, Yoshitaka Saito, Wayne Menary, Youping Deng, Lucy Lee, Esmeralda Jiminez, Ayuki Watanabe, Nikos C. Kyrpides, Natasha Mohan, Angelika Pupiec, Dedan Githae, Simone Cawthorne, Jonathan A. Eisen, Tomoki Iwashiro, Chiaki Homma, Thomas Saw Aung, Laura Molina, Marcus H. Y. Leung, Ophélie Da Silva, Yan Ling Wong, Hosna Noorzi, Mario Moreno, Alina Butova, Leming Shi, Brian W. Wong, Sarah S. Jackson, Moses Lin, Annabelle Meagher, Pujita Das, Catherine Burke, Mitsuki Ota, Maria Domenica Moccia, Nicolas Sprinsky, Catherine E. Pugh, David C. Green, Fazlina Fauzi, Erdenetsetseg Batdelger, Annie Geiger, Valeria Ventorino, Tolulope Oluwadare, Delisia Cuebas, Catalina Truong, Leonardo Posada, Michael Angelov, Tathiane M. Malta, Amanda Ng, Francesca Nadalin, Arya Hawkins-Zafarnia, Yuh Shiwa, Athena Mitsios, Milton Ozório Moraes, Manolo Laiola, Kalyn Ali, Jaden J.A. Hastings, Ikuto Saito, Maheen Shakil, Chisato Suzuki, Elena M. Vayndorf, Hubert Rehrauer, Ajay Menon, Kaitlan Russell, Aliyah Shari, Rebecca Smith, Gregorio Iraola, Max Priestman, Alan Briones, Silver A. Wolf, Camila Gonzalez-Poblete, Eleonora De Lazzari, Shirley Chiu, Michelle Ki, Irene Hoxie, Marianne Jaubert, Ayantu Jinfessa, Ryan J. King, Nghiem Xuan Hoan, Jalia Bynoe, Jacob Friedman, Aneisa Ramcharan, Pablo Fresia, Cristina Muñoz, Muhammad Afaq, Anyi Tang, Médine Benchouaia, Isabella Kuniko T. Takenaka, Anastasia Chasapi, Areeg Naeem, Hannah Benisty, Cecilia N. Cossio, Nathalie Hüsser, Mahfuza Sabina, Thais S. Sabedot, JoAnn Jacobs, Camila P. E. de Souza, Manuela Oliveira, Jean-Pierre Bouly, Mariko Usui, Wilson Miranda, Natalia Marciniak, Hiram Caballero, Samuel Weekes, Alexandra B. Graf, Emily Leong, Tatyana Nikolayeva, Dominique Thomas, Charlotte Greselle, Cecilia Salazar, Sreya Ray Chaudhuri, Kevin Becher, Sandra Roth, Ryusei Miura, Kari Oline Bøifot, Dimitri Manoir, Oliver Toth, Chandrima Bhattacharya, Manuel Perez, Isha Lamba, Takafumi Tsurumaki, Timothy D. Read, Anna-Lena M. Schinke, Ryan Sankar, Le Huu Song, Narasimha Rao Nedunuri, Emmanuel Dias-Neto, Ana Flávia Costa, Adiell Melamed, Christelle Desnues, Natalie R. Davidson, Aaron E. Darling, Hyung Jun Kim, Josephine Galipon, Jacqueline Orrego, Dimitar Vassilev, Michael Huber, Nur Hazlin Hazrin-Chong, Gaston H. Gonnet, Kaymisha Knights, Osman U. Sezerman, Dmitry Meleshko, Eunice Thambiraja, Jingcheng Yang, Aubin Fleiss, Gloria Nguyen, Katelyn Jackson, Nuria Aventin, Stephanie L. Hyland, Andrea Hässig, Catharine Aquino, Simona Lysakova, Israel O. Osuolale, Kasia Sluzek, Rania Siam, Alina Frolova, Samuel Hernandez, Yui Him Lo, Bazartseren Boldgiv, Ben Young, Maryna Korshevniuk, Majelia Ampadu, Yuk Man Tang, Amanda L. Muehlbauer, Sade Thomas, Gabriel Figueroa, Alexis Rivera, Lisbeth Pineda, Alexandra Dutan, Jennifer M. Tran, Chris K. Deng, Vedbar S. Khadka, Paola Florez de Sessions, Elizabeth Humphries, Hugues Richard, Hiba Naveed, Nora C. Toussaint, Mahshid Khavari, Maria del Mar Vivanco Ruiz, Antonin Thiébaut, Nicolás Rascovan, Marius Dybwad, Orhan Özcan, Lawrence Kwong, David Danko, Shaira Khan, Andrea Tassinari, Silvia Beurmann, Tsoi Ying Lai, Nanami Kubota, Tieliu Shi, Diana Chicas, Evan E. Afshin, Hirokazu Yano, Jonas Krebs, Mayuko Nakagawa, Hyun Jung Lee, Irene González Navarrete, Rachid Ounit, Lucia E. Alvarado-Arnez, Masaki Nasu, Allison Chan, Harilanto Andrianjakarivony, Jennifer Amachee, Mahdi Taye, Wan Chiew Ng, Kathryn O’Brien, Shino Ishikawa, Tristan Bitard-Feildel, Sora Takagi, Felix Hartkopf, Niamh B. O’Hara, Marcos A. S. Fonseca, Subhamitra Pakrashi, Amrit Kaur, Eva Hell, Patricia Vera-Wolf, Naimah Munim, Luiza Ferreira de Araújo, Mizuki Igarashi, Brianna Pompa-Hogan, Alessandra Carbone, Anne-Sophie Benoiston, Eric Helfrich, Michael A. Suarez-Villamil, Omar O. Abudayyeh, Natasha Abdullah, Jaime J. Fuentes, Juan Carlos Forero, Tetiana Yeskova, Denis Bertrand, Sambhawa Priya, Denisse Maldonado, Agier Nicolas, Ana Valeria B Castro, Starr Chatziefthimiou, André Kahles, Aaishah Francis, Fernanda Arredondo, Emilio Tarcitano, Irvind Buttar, Alex Alexiev, Jennifer Molinet, Sarah Shalaby, Itunu A. Oluwadare, Jason Sperry, Katrin Bakhl, Ana M. Cañas, Sofia Ahsanuddin, Miar Elaskandrany, Elodie Laine, Sven Bönigk, Johannes Werner, Stephen Eduard Boja Ruiz, Gargi Dayama, Paulina Buczansla, Brandon Valentine, Bharath Prithiviraj, Toni Bode, Stas Zubenko, Jake Cohen, Guilllaume Jospin, Zulena Saravi, Per O. Ljungdahl, Inderjit Kaur, Mauricio Moldes, Giuseppe KoLoMonaco, Denise Syndercombe Court, Sonia Bouchard, Sonia Losim, Sookwon Moon, Heba Shaaban, Suraj Patel, Sibo Zhu, Sarh Aly, Arif Asyraf Md Supie, LaShonda Dorsey, Juan Guerra, François Baudon, Rantimi A. Olawoyin, Alexia Bordigoni, Iqra Faiz, Mathilde Garcia, Gabriella Mason-Buck, María Gabriela Portilla, Niranjan Nagarajan, Fumie Takahara, Nancy Merino, Watson Andrew, Gina Kim, Yuma Sato, Hyenah Shim, Marie-Laure Jerier, Affifah Saadah Ahmad Kassim, Katerina Kuchin, Daniel Butler, Paweł P. Łabaj, Nadezhda Kobko-Litskevitch, Emmanuel F. Mongodin, Yuto Togashi, Paula Rodríguez, Pilar Lopez Hernandez, Xiaoqing Chen, Maria A. Sierra, Olga Nikolayeva, Manon Loubens, Colleen Conger, Hikaru Shirahata, Chenhao Li, Timothy Donahoe, Youngja Park, Lucia Elena Alvarado Arnez, Salama Chaker, Francisco Chavez, Alessandra Breschi, Jorge L. Sanchez, Kaung Myat San, Nayra Aguilar Rojas, Marcos Abraao, Kai Sasaki, Bryan Nazario, Olena Yemets, Klas I. Udekwu, Lynn M. Schriml, Anisia Peters, Aliaksei Holik, Mark Hernandez, Emile Faure, Malay Bhattacharyya, Josef W. Moser, Núria Andreu Somavilla, María Mercedes Zambrano, Kannan Rajendran, Gabriela E. Albuquerque, Tao Qing, Kazutoshi Tsuda, Ymke De Jong, Princess Osma, Mayra Arauco Livia, Javier Quilez Oliete, Carl Chrispin, Hyun Woo Joo, Ingrid Lafontaine, Nala An, Seisuke Sato, Felipe Segato Dezem, Andrew Maltez Thomas, Alexandre Desert, Xiao Wen Cai, O. Osuolale, Jun Wu, Coral Pardo-Esté, Courtney Robinson, Yuri Matsuzaki, Marina Nieto-Caballero, Cem Meydan, Ralph Schlapbach, Mark Menor, Sofia Castro, Rachel Kwong, Brittany Blyther, Olexandr Lykhenko, Jason R. Schriml, Christian Brion, Jenessa Orpilla, Juan A. Ugalde, Elsy Mankah Ngwa, Álvaro Aranguren, Lauren Mak, Matías Giménez, Ashanti Narce, Torsten Semmler, Stefan I. Tsonev, Abdollahi Nika, Katherine E. Dahlhausen, Monika Devi, Gunnar Rätsch, Oasima Muner, Carla Bello, Muhammad Al-Fath Amran, Anyelic Rosario, Melissa Ortega, Andrea Patrignani, Ante Peros, Elias McComb, Ryo Sato, Ireen Alam, Clara N. Dias, Soma Tanaka, Dayana Calderon, Ran Blekhman, Mathilde Mignotte, Alicia Boyd, Jochen Hecht, Thomas Neff, Xinzhao Tong, Josue Alicea, Kiara Olmeda, Sonia Marinovic, Carme Arnan, Kohei Ito, Samantha L. Goldman, Marianna S. Serpa, Renee Richer, Kaisei Sato, Jordana M. Silva, Akash Keluth Chavan, Sangwan Kim, Laís Pereira Ferreira, Sophie Vacant, Nowshin Sayara, Haruo Suzuki, Madeline Leahy, Juan C. Severyn, Sierra Vincent, Masaru Tomita, Maliha Mamun, Lucinda B. Davenport, Gabriella Oken, Dagmara Lewandowska, Gustavo Adolfo Malca Salas, Andrii Kuklin, Tyler Wong, Charlie Feigin, Eric Minwei Liu, Sonia L. Ghose, Daniela Bezdan, Antonietta La Storia, Juan P. Escalera-Antezana, Nuno Rufino de Sousa, Samuel M. Gerner, Weill Cornell Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Genome Institute of Singapore (GIS), Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), AUTRES, Massachusetts Institute of Technology (MIT), Indian Statistical Institute [Kolkata], University of Minnesota System, Universidad Andrés Bello [Santiago] (UNAB), California State University [Sacramento], University of Naples Federico II, University of Hawaii, Institut méditerranéen d'océanologie (MIO), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN), Medical Genomics Group, University College of London [London] (UCL)-UCL Cancer Institute, Norwegian Defence Research Establishment (FFI), Lund University [Lund], Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, University of Vienna [Vienna], King‘s College London, University of Colorado [Boulder], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur Korea - Institut Pasteur de Corée, Fudan University [Shanghai], City University of Hong Kong [Hong Kong] (CUHK), Stockholm University, University of Maryland School of Medicine, University of Maryland System, Fundação Oswaldo Cruz (FIOCRUZ), University of São Paulo (USP), Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Barcelona Institute of Science and Technology (BIST), Elizade University, Acibadem Mehmet Ali Aydınlar University, Paléogénomique microbienne - Microbial paleogenomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Robert Koch Institute [Berlin] (RKI), East China Normal University [Shangaï] (ECNU), Cairo University, Vietnamese-German Center for Medical Research, Keio University, Université du Vermont, Universidad del Desarrollo, University of Sofia, University of Alaska [Fairbanks] (UAF), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Corporación Corpogen-Research Center, Biologie Computationnelle et Quantitative = Laboratory of Computational and Quantitative Biology (LCQB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Weill Cornell Medicine [Cornell University], Cornell University [New York], University of Naples Federico II = Università degli studi di Napoli Federico II, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Universidade de São Paulo = University of São Paulo (USP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Софийски университет = Sofia University, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad Andrés Bello - UNAB (CHILE), Acibadem University Dspace, Danko, D., Bezdan, D., Afshin, E. E., Ahsanuddin, S., Bhattacharya, C., Butler, D. J., Chng, K. R., Donnellan, D., Hecht, J., Jackson, K., Kuchin, K., Karasikov, M., Lyons, A., Mak, L., Meleshko, D., Mustafa, H., Mutai, B., Neches, R. Y., Ng, A., Nikolayeva, O., Nikolayeva, T., Png, E., Ryon, K. A., Sanchez, J. L., Shaaban, H., Sierra, M. A., Thomas, D., Young, B., Abudayyeh, O. O., Alicea, J., Bhattacharyya, M., Blekhman, R., Castro-Nallar, E., Canas, A. M., Chatziefthimiou, A. D., Crawford, R. W., De Filippis, F., Deng, Y., Desnues, C., Dias-Neto, E., Dybwad, M., Elhaik, E., Ercolini, D., Frolova, A., Gankin, D., Gootenberg, J. S., Graf, A. B., Green, D. C., Hajirasouliha, I., Hastings, J. J. A., Hernandez, M., Iraola, G., Jang, S., Kahles, A., Kelly, F. J., Knights, K., Kyrpides, N. C., Labaj, P. P., Lee, P. K. H., Leung, M. H. Y., Ljungdahl, P. O., Mason-Buck, G., Mcgrath, K., Meydan, C., Mongodin, E. F., Moraes, M. O., Nagarajan, N., Nieto-Caballero, M., Noushmehr, H., Oliveira, M., Ossowski, S., Osuolale, O. O., Ozcan, O., Paez-Espino, D., Rascovan, N., Richard, H., Ratsch, G., Schriml, L. M., Semmler, T., Sezerman, O. U., Shi, L., Shi, T., Siam, R., Song, L. H., Suzuki, H., Court, D. S., Tighe, S. W., Tong, X., Udekwu, K. I., Ugalde, J. A., Valentine, B., Vassilev, D. I., Vayndorf, E. M., Velavan, T. P., Wu, J., Zambrano, M. M., Zhu, J., Zhu, S., Mason, C. E., Abdullah, N., Abraao, M., Adel, A. -H., Afaq, M., Al-Quaddoomi, F. S., Alam, I., Albuquerque, G. E., Alexiev, A., Ali, K., Alvarado-Arnez, L. E., Aly, S., Amachee, J., Amorim, M. G., Ampadu, M., Amran, M. A. -F., An, N., Andrew, W., Andrianjakarivony, H., Angelov, M., Antelo, V., Aquino, C., Aranguren, A., Araujo, L. F., Vasquez Arevalo, H. F., Arevalo, J., Arnan, C., Alvarado Arnez, L. E., Arredondo, F., Arthur, M., Asenjo, F., Aung, T. S., Auvinet, J., Aventin, N., Ayaz, S., Baburyan, S., Bakere, A. -M., Bakhl, K., Bartelli, T. F., Batdelger, E., Baudon, F., Becher, K., Bello, C., Benchouaia, M., Benisty, H., Benoiston, A. -S., Benson, J., Benitez, D., Bernardes, J., Bertrand, D., Beurmann, S., Bitard-Feildel, T., Bittner, L., Black, C., Blanc, G., Blyther, B., Bode, T., Boeri, J., Boldgiv, B., Bolzli, K., Bordigoni, A., Borrelli, C., Bouchard, S., Bouly, J. -P., Boyd, A., Branco, G. P., Breschi, A., Brindefalk, B., Brion, C., Briones, A., Buczansla, P., Burke, C. M., Burrell, A., Butova, A., Buttar, I., Bynoe, J., Bonigk, S., Boifot, K. O., Caballero, H., Cai, X. W., Calderon, D., Cantillo, A., Carbajo, M., Carbone, A., Cardenas, A., Carrillo, K., Casalot, L., Castro, S., Castro, A. V., Castro, A., Castro, A. V. B., Cawthorne, S., Cedillo, J., Chaker, S., Chalangal, J., Chan, A., Chasapi, A. I., Chatziefthimiou, S., Chaudhuri, S. R., Chavan, A. K., Chavez, F., Chem, G., Chen, X., Chen, M., Chen, J. -W., Chernomoretz, A., Chettouh, A., Cheung, D., Chicas, D., Chiu, S., Choudhry, H., Chrispin, C., Ciaramella, K., Cifuentes, E., Cohen, J., Coil, D. A., Collin, S., Conger, C., Conte, R., Corsi, F., Cossio, C. N., Costa, A. F., Cuebas, D., D'Alessandro, B., Dahlhausen, K. E., Darling, A. E., Das, P., Davenport, L. B., David, L., Davidson, N. R., Dayama, G., Delmas, S., Deng, C. K., Dequeker, C., Desert, A., Devi, M., Dezem, F. S., Dias, C. N., Donahoe, T. R., Dorado, S., Dorsey, L., Dotsenko, V., Du, S., Dutan, A., Eady, N., Eisen, J. A., Elaskandrany, M., Epping, L., Escalera-Antezana, J. P., Ettinger, C. L., Faiz, I., Fan, L., Farhat, N., Faure, E., Fauzi, F., Feigin, C., Felice, S., Ferreira, L. P., Figueroa, G., Fleiss, A., Flores, D., Velasco Flores, J. L., Fonseca, M. A. S., Foox, J., Forero, J. C., Francis, A., French, K., Fresia, P., Friedman, J., Fuentes, J. J., Galipon, J., Garcia, M., Garcia, L., Garcia, C., Geiger, A., Gerner, S. M., Ghose, S. L., Giang, D. P., Gimenez, M., Giovannelli, D., Githae, D., Gkotzis, S., Godoy, L., Goldman, S., Gonnet, G. H., Gonzalez, J., Gonzalez, A., Gonzalez-Poblete, C., Gray, A., Gregory, T., Greselle, C., Guasco, S., Guerra, J., Gurianova, N., Haehr, W., Halary, S., Hartkopf, F., Hawkins-Zafarnia, A., Hazrin-Chong, N. H., Helfrich, E., Hell, E., Henry, T., Hernandez, S., Hernandez, P. L., Hess-Homeier, D., Hittle, L. E., Hoan, N. X., Holik, A., Homma, C., Hoxie, I., Huber, M., Humphries, E., Hyland, S., Hassig, A., Hausler, R., Husser, N., Petit, R. A., Iderzorig, B., Igarashi, M., Iqbal, S. B., Ishikawa, S., Ishizuka, S., Islam, S., Islam, R., Ito, K., Ito, S., Ito, T., Ivankovic, T., Iwashiro, T., Jackson, S., Jacobs, J., James, M., Jaubert, M., Jerier, M. -L., Jiminez, E., Jinfessa, A., De Jong, Y., Joo, H. W., Jospin, G., Kajita, T., Ahmad Kassim, A. S., Kato, N., Kaur, A., Kaur, I., de Souza Gomes Kehdy, F., Khadka, V. S., Khan, S., Khavari, M., Ki, M., Kim, G., Kim, H. J., Kim, S., King, R. J., Kolomonaco, G., Koag, E., Kobko-Litskevitch, N., Korshevniuk, M., Kozhar, M., Krebs, J., Kubota, N., Kuklin, A., Kumar, S. S., Kwong, R., Kwong, L., Lafontaine, I., Lago, J., Lai, T. Y., Laine, E., Laiola, M., Lakhneko, O., Lamba, I., de Lamotte, G., Lannes, R., De Lazzari, E., Leahy, M., Lee, H., Lee, Y., Lee, L., Lemaire, V., Leong, E., Lewandowska, D., Li, C., Liang, W., Lin, M., Lisboa, P., Litskevitch, A., Liu, E. M., Liu, T., Livia, M. A., Lo, Y. H., Losim, S., Loubens, M., Lu, J., Lykhenko, O., Lysakova, S., Mahmoud, S., Majid, S. A., Makogon, N., Maldonado, D., Mallari, K., Malta, T. M., Mamun, M., Manoir, D., Marchandon, G., Marciniak, N., Marinovic, S., Marques, B., Mathews, N., Matsuzaki, Y., Matthys, V., May, M., Mccomb, E., Meagher, A., Melamed, A., Menary, W., Mendez, K. N., Mendez, A., Mendy, I. M., Meng, I., Menon, A., Menor, M., Meoded, R., Merino, N., Miah, K., Mignotte, M., Miketic, T., Miranda, W., Mitsios, A., Miura, R., Miyake, K., Moccia, M. D., Mohan, N., Mohsin, M., Moitra, K., Moldes, M., Molina, L., Molinet, J., Molomjamts, O. -E., Moniruzzaman, E., Moon, S., de Oliveira Moraes, I., Moreno, M., Mosella, M. S., Moser, J. W., Mozsary, C., Muehlbauer, A. L., Muner, O., Munia, M., Munim, N., Muscat, M., Mustac, T., Munoz, C., Nadalin, F., Naeem, A., Nagy-Szakal, D., Nakagawa, M., Narce, A., Nasu, M., Navarrete, I. G., Naveed, H., Nazario, B., Nedunuri, N. R., Neff, T., Nesimi, A., Ng, W. C., Ng, S., Nguyen, G., Ngwa, E., Nicolas, A., Nicolas, P., Nika, A., Noorzi, H., Nosrati, A., Nunes, D. N., O'Brien, K., O'Hara, N. B., Oken, G., Olawoyin, R. A., Oliete, J. Q., Olmeda, K., Oluwadare, T., Oluwadare, I. A., Ordioni, N., Orpilla, J., Orrego, J., Ortega, M., Osma, P., Osuolale, I. O., Osuolale, O. M., Ota, M., Oteri, F., Oto, Y., Ounit, R., Ouzounis, C. A., Pakrashi, S., Paras, R., Pardo-Este, C., Park, Y. -J., Pastuszek, P., Patel, S., Pathmanathan, J., Patrignani, A., Perez, M., Peros, A., Persaud, S., Peters, A., Phillips, A., Pineda, L., Pizzi, M. P., Plaku, A., Pompa-Hogan, B., Portilla, M. G., Posada, L., Priestman, M., Prithiviraj, B., Priya, S., Pugdeethosal, P., Pugh, C. E., Pulatov, B., Pupiec, A., Pyrshev, K., Qing, T., Rahiel, S., Rahmatulloev, S., Rajendran, K., Ramcharan, A., Ramirez-Rojas, A., Rana, S., Ratnanandan, P., Read, T. D., Rehrauer, H., Richer, R., Rivera, A., Rivera, M., Robertiello, A., Robinson, C., Rodriguez, P., Rojas, N. A., Roldan, P., Rosario, A., Roth, S., Ruiz, M., Boja Ruiz, S. E., Russell, K., Rybak, M., Sabedot, T. S., Sabina, M., Saito, I., Saito, Y., Malca Salas, G. A., Salazar, C., San, K. M., Sanchez, J., Sanchir, K., Sankar, R., de Souza Santos, P. T., Saravi, Z., Sasaki, K., Sato, Y., Sato, M., Sato, S., Sato, R., Sato, K., Sayara, N., Schaaf, S., Schacher, O., Schinke, A. -L. M., Schlapbach, R., Schori, C., Schriml, J. R., Segato, F., Sepulveda, F., Serpa, M. S., De Sessions, P. F., Severyn, J. C., Shakil, M., Shalaby, S., Shari, A., Shim, H., Shirahata, H., Shiwa, Y., Da Silva, O., Silva, J. M., Simon, G., Singh, S. K., Sluzek, K., Smith, R., So, E., Andreu Somavilla, N., Sonohara, Y., Rufino de Sousa, N., Souza, C., Sperry, J., Sprinsky, N., Stark, S. G., La Storia, A., Suganuma, K., Suliman, H., Sullivan, J., Supie, A. A. M., Suzuki, C., Takagi, S., Takahara, F., Takahashi, N., Takahashi, K., Takeda, T., Takenaka, I. K., Tanaka, S., Tang, A., Man Tang, Y., Tarcitano, E., Tassinari, A., Taye, M., Terrero, A., Thambiraja, E., Thiebaut, A., Thomas, S., Thomas, A. M., Togashi, Y., Togashi, T., Tomaselli, A., Tomita, M., Tomita, I., Toth, O., Toussaint, N. C., Tran, J. M., Truong, C., Tsonev, S. I., Tsuda, K., Tsurumaki, T., Tuz, M., Tymoshenko, Y., Urgiles, C., Usui, M., Vacant, S., Vann, L. E., Velter, F., Ventorino, V., Vera-Wolf, P., Vicedomini, R., Suarez-Villamil, M. A., Vincent, S., Vivancos-Koopman, R., Wan, A., Wang, C., Warashina, T., Watanabe, A., Weekes, S., Werner, J., Westfall, D., Wieler, L. H., Williams, M., Wolf, S. A., Wong, B., Wong, Y. L., Wong, T., Wright, R., Wunderlin, T., Yamanaka, R., Yang, J., Yano, H., Yeh, G. C., Yemets, O., Yeskova, T., Yoshikawa, S., Zafar, L., Zhang, Y., Zhang, S., Zhang, A., Zheng, Y., and Zubenko, S.

Subjects
Urban Population, Drug Resistance, Sequence assembly, Microbiologia, microbiome, global health, computer.software_genre, Medical and Health Sciences, shotgun sequencing, BGC, 0302 clinical medicine, Databases, Genetic, 11. Sustainability, Global health, AMR, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, built environment, metagenome, antimicrobial resistance, NGS, de novo assembly, biology, Shotgun sequencing, Microbiota, built Environment, Bacterial, Biodiversity, Biological Sciences, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infection, Biotechnology, Geospatial analysis, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Article, General Biochemistry, Genetics and Molecular Biology, Databases, 03 medical and health sciences, Antibiotic resistance, Genetic, Drug Resistance, Bacterial, International MetaSUB Consortium, Genetics, Humans, Microbiome, 030304 developmental biology, Human Genome, 06 Biological Sciences, 15. Life on land, biology.organism_classification, Resistènica als medicaments antiinfecciosos, SAÚDE PÚBLICA, Genòmica, 13. Climate action, Evolutionary biology, Metagenomics, Antimicrobial Resistance, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, computer, 030217 neurology & neurosurgery, Archaea, Developmental Biology
Abstract

Summary We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities., Graphical abstract, Highlights • Cities possess a consistent “core” set of non-human microbes • Urban microbiomes echo important features of cities and city-life • Antimicrobial resistance genes are widespread in cities • Cities contain many novel bacterial and viral species, This systematic, worldwide catalog of urban microbiomes represents a metagenomic atlas important for understanding the ecology, virulence, and antibiotic resistance of city-specific microbial communities.

Published
2021
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8. Bifid T waves on the ECG and genetic variation in calcium channel voltage‐dependent beta 2 subunit gene ( CACNB2 ) in acute Kawasaki disease

Author

Chisato Shimizu, Eileen Png, Jane C. Burns, Jun Oyamada, Martin L. Hibberd, Matthew R. Williams, James C. Perry, Adriana H. Tremoulet, and Jihoon Kim

Subjects
Male, medicine.medical_specialty, Calcium Channels, L-Type, Genome-wide association study, Mucocutaneous Lymph Node Syndrome, 030204 cardiovascular system & hematology, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), 030225 pediatrics, Internal medicine, T wave, Genetic variation, Genotype, medicine, Humans, Repolarization, Genetic Predisposition to Disease, Radiology, Nuclear Medicine and imaging, Polymorphism, Genetic, Voltage-dependent calcium channel, business.industry, Calcium channel, Genetic Variation, Infant, General Medicine, Endocrinology, Echocardiography, Child, Preschool, Acute Disease, Pediatrics, Perinatology and Child Health, Female, Surgery, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, Genome-Wide Association Study
Abstract

Author(s): Oyamada, Jun; Shimizu, Chisato; Kim, Jihoon; Williams, Matthew R; Png, Eileen; Hibberd, Martin L; Tremoulet, Adriana H; Perry, James C; Burns, Jane C | Abstract: BackgroundWe previously described the association of genetic variants in calcium channel genes and susceptibility to Kawasaki disease (KD), an acute, self-limited vasculitis, and the most common cause of acquired cardiac disease in children. Abnormal repolarization of cardiomyocytes and changes in T wave morphology have been reported in KD but have not been studied systematically.MethodsWe analyzed acute and convalescent ECG T wave morphology in two independent cohorts of KD subjects and studied the association between bifid T waves and genetic variants in previously reported genes with SNVs associated with cardiac repolarization.ResultsBifid T waves in limb leads were identified in 24% and 27% of two independent cohorts of acute KD subjects. Calcium channel voltage-dependent beta 2 subunit gene (CACNB2) (rs1409207) showed association with bifid T waves in both cohorts (nominal P = .04 and P = .0003, respectively). This CACNB2 polymorphism also showed association with KD susceptibility in a previously published KD genome wide association study data (nominal P = .009).ConclusionThis genotype/phenotype association study uncovered a variant in CACNB2 that may be associated with both KD susceptibility and bifid T waves, a novel signature of altered myocardial repolarization. The present study combined with published reports suggests that genetic variants in calcium channels and intracellular calcium signaling play a prominent role in shaping susceptibility to KD.

Published
2018
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9. Extensive Ethnic Variation and Linkage Disequilibrium at the

Author

Sietse Q, Nagelkerke, Carline E, Tacke, Willemijn B, Breunis, Michael W T, Tanck, Judy, Geissler, Eileen, Png, Long T, Hoang, Joris, van der Heijden, Ahmad N M, Naim, Rae S M, Yeung, Michael L, Levin, Victoria J, Wright, David P, Burgner, Anne-Louise, Ponsonby, Justine A, Ellis, Rolando, Cimaz, Chisato, Shimizu, Jane C, Burns, Karin, Fijnvandraat, C Ellen, van der Schoot, Timo K, van den Berg, Martin, de Boer, Sonia, Davila, Martin L, Hibberd, Taco W, Kuijpers, and Isabelle, Kone-Paut

Subjects
DNA Copy Number Variations, Genotype, Gene Expression Profiling, Receptors, IgG, Immunology, Mucocutaneous Lymph Node Syndrome, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Fc-gamma receptor, immunogenetics, Gene Frequency, Haplotypes, Genetic Loci, FCGR polymorphism, Case-Control Studies, Kawasaki disease (KD), Ethnicity, Odds Ratio, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Genome-Wide Association Study, Original Research
Abstract

The human Fc-gamma receptors (FcγRs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All human low-affinity FcγRs are encoded by the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) and gene copy number variants. This locus is notoriously difficult to genotype and high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at the FCGR2/3 locus in >4,000 individuals to define linkage disequilibrium (LD) and allele frequencies in different populations. Strong LD and extensive ethnic variation in allele frequencies was found across the locus. LD was strongest for the FCGR2C-ORF haplotype (rs759550223+rs76277413), which leads to expression of FcγRIIc. In Europeans, the FCGR2C-ORF haplotype showed strong LD with, among others, rs201218628 (FCGR2A-Q27W, r2 = 0.63). LD between these two variants was weaker (r2 = 0.17) in Africans, whereas the FCGR2C-ORF haplotype was nearly absent in Asians (minor allele frequency

Published
2018

10. Comparison of self-reported and register-based hospital medical data on comorbidities in women

Author

Kee Seng Chia, Kamila Czene, Hui Miao, Per Hall, Shajedur Rahman Shawon, Li Yan Lim, Chuen Seng Tan, Jonas F. Ludvigsson, Mikael Eriksson, Mikael Hartman, Jingmei Li, Peh Joo Ho, and Eileen Png

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, Databases, Factual, Myocardial Infarction, lcsh:Medicine, Comorbidity, Logistic regression, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Breast cancer, Cohen's kappa, Internal medicine, medicine, Mammography, Humans, Registries, lcsh:Science, Stroke, Aged, Aged, 80 and over, Heart Failure, Sweden, Multidisciplinary, medicine.diagnostic_test, business.industry, Medical record, lcsh:R, Middle Aged, medicine.disease, Polycystic ovary, 030104 developmental biology, Logistic Models, Hypertension, lcsh:Q, Female, Self Report, business, 030217 neurology & neurosurgery, Kappa
Abstract

Breast cancer patients commonly present with comorbidities which are known to influence treatment decisions and survival. We aim to examine agreement between self-reported and register-based medical records (National Patient Register [NPR]). Ascertainment of nine conditions, using individually-linked data from 64,961 women enrolled in the Swedish KARolinska MAmmography Project for Risk Prediction of Breast Cancer (KARMA) study. Agreement was assessed using observed proportion of agreement (overall agreement), expected proportion of agreement, and Cohen’s Kappa statistic. Two-stage logistic regression models taking into account chance agreement were used to identify potential predictors of overall agreement. High levels of overall agreement (i.e. ≥86.6%) were observed for all conditions. Substantial agreement (Cohen’s Kappa) was observed for myocardial infarction (0.74), diabetes (0.71) and stroke (0.64) between self-reported and NPR data. Moderate agreement was observed for preeclampsia (0.51) and hypertension (0.46). Fair agreement was observed for heart failure (0.40) and polycystic ovaries or ovarian cysts (0.27). For hyperlipidemia (0.14) and angina (0.10), slight agreement was observed. In most subgroups we observed negative specific agreement of >90%. There is no clear reference data source for ascertainment of conditions. Negative specific agreement between NPR and self-reported data is consistently high across all conditions.

Published
2018

11. PRINCESS: Privacy-protecting Rare disease International Network Collaboration via Encryption through Software guard extensionS

Author

Kristin E. Lauter, Cinnamon S. Bloss, Süleyman Cenk Sahinalp, David Lloyd, Eileen Png, Dov Fox, Feng Chen, Lucila Ohno-Machado, Jane C. Burns, Victoria J. Wright, Hai Yang, Shuang Wang, Yao Lu, Martin L. Hibberd, Sijie Ding, Jihoon Kim, Xiaoqian Jiang, Amalio Telenti, Chisato Shimizu, and Stegle, Oliver

Subjects
0301 basic medicine, Technology, Computer science, 02 engineering and technology, computer.software_genre, Encryption, Biochemistry, Mathematical Sciences, Software, GWAS, POPULATION, Guard (information security), Genomics, Biological Sciences, LOGISTIC-REGRESSION, Original Papers, Computer Science Applications, Computational Mathematics, Computational Theory and Mathematics, Privacy, Physical Sciences, Computer Science, Interdisciplinary Applications, KAWASAKI-DISEASE, Life Sciences & Biomedicine, Statistics and Probability, Biochemistry & Molecular Biology, DATASETS, Bioinformatics, Statistics & Probability, 0206 medical engineering, RELATIVES, Mucocutaneous Lymph Node Syndrome, COMPUTATION, Computer security, Biochemical Research Methods, 03 medical and health sciences, Rare Diseases, Information and Computing Sciences, Applied mathematics, Humans, GENOME-WIDE ASSOCIATION, Molecular Biology, 01 Mathematical Sciences, Computer Security, Genetic Association Studies, 08 Information And Computing Sciences, International network, Science & Technology, business.industry, Homomorphic encryption, 06 Biological Sciences, 030104 developmental biology, Biotechnology & Applied Microbiology, Computer Science, Mathematical & Computational Biology, business, computer, Mathematics, 020602 bioinformatics
Abstract

Motivation We introduce PRINCESS, a privacy-preserving international collaboration framework for analyzing rare disease genetic data that are distributed across different continents. PRINCESS leverages Software Guard Extensions (SGX) and hardware for trustworthy computation. Unlike a traditional international collaboration model, where individual-level patient DNA are physically centralized at a single site, PRINCESS performs a secure and distributed computation over encrypted data, fulfilling institutional policies and regulations for protected health information. Results To demonstrate PRINCESS’ performance and feasibility, we conducted a family-based allelic association study for Kawasaki Disease, with data hosted in three different continents. The experimental results show that PRINCESS provides secure and accurate analyses much faster than alternative solutions, such as homomorphic encryption and garbled circuits (over 40 000× faster). Availability and Implementation https://github.com/achenfengb/PRINCESS_opensource Supplementary information Supplementary data are available at Bioinformatics online.

Published
2017

12. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma

Author

Tina T. Wong, Yaan Fun Chong, Kathryn P. Burdon, Sancy Low, Ningli Wang, Tuan Anh Tran, Emma Rusmayani, Alexander C Day, Kei Tashiro, Tam Thi Luu, Aye Thi Han, Christine A. Kiire, Nay Lin Oo, Hiroshi Sakai, Ewa Kosior-Jarecka, Sripriya Sarangapani, Mimiwati Zahari, Widya Artini Wiyogo, Seng-Chee Loon, Rigo Daniel Reyes, Rrima Dada, Robert Ritch, E-Shyong Tai, Jin-Xin Bei, Ren-Yi Wu, Balekudaru Shantha, Leyla Al-Jasim, Giulia Consolandi, Ya Xing Wang, Saleh A. Al-Obeidan, Tomasz Zarnowski, Shazia Micheal, Maria Luisa Guevara-Fujita, Raquel Quino, Yuzhen Jiang, Monisha E. Nongpiur, Yik Y. Teo, Francesca Pasutto, Hailin Meng, Mani Baskaran, Shigeru Kinoshita, Sunee Chansangpetch, Clement C Y Tham, Eranga N. Vithana, Paul J. Foster, Greet J. Boland, Deepak P. Edward, Young Hoon Hwang, Daniel H. Su, Ricardo Fujita, Huan Nguyen Pham, Yong Ho Sohn, Mark Seielstad, Rengaraj Venkatesh, Paul Mitchell, Morio Ueno, Chaw Chaw Khaing, Thanh Thu Nguyen, Celso Tello, Anita S. Chan, Muhammad Imran Khan, Vernon Yong, Eileen Png, Takanori Mizoguchi, Nguyen Van Vinh Chau, Soo Hong Chew, Laura Dallorto, Chunyan Qiao, Donald T.H. Tan, Norlina Ramli, Mei Chin Lee, Rahat Husain, Kar Seng Sim, Sarah J. Dunstan, Kyu Hyung Park, Stephen A Vernon, Thi Nguyen, Rodolfo A. Perez-Grossmann, Jelinar Mohamed-Noor, Jeeyun Ahn, David Lozano-Giral, Tan Do, Yin Mon Aung, Prin Rojanapongpun, Naris Kitnarong, Martin L. Hibberd, Chan-Yun Kim, Mineo Ozaki, Manchima Makornwattana, Ronnie George, José Paulo Cabral de Vasconcellos, Huong T T Bui, Chona S Liao, Saw Htoo Set, Chi Pui Pang, Paul T K Chew, Aliza Jap, Naushin Waseem, Toshiaki Kubota, Tanuj Dada, Hyoung Won Bae, Tin Aung, Ricardo Y. Abe, Khin Thida Oo, Periasamy Sundaresan, Jose Maria Martinez, Visanee Tantisevi, Shomi S. Bhattacharya, Anneke I. den Hollander, Vira Wardhana Istiantoro, Rohit Shetty, Boonsong Wanichwecharungruang, Liang Xu, Seng Kheong Fang, Masakazu Nakano, E. Randy Craven, Richard P. Ebstein, Ching-Lin Ho, Arkasubhra Ghosh, Jeanne J. Ogle, Hongyan Jia, Muneeb A. Faiq, Yasuo Kurimoto, Michiko Yonahara, Richard Stead, Li Jia Chen, Satoko Nakano, Anavaj Sakuntabhai, Masako Kuroda, Thayanithi Sandragasu, Leonard W. Yip, Lerprat Mangkornkanokpong, Pancy O. S. Tam, Seang-Mei Saw, Ching-Yu Cheng, Saravanan Vijayan, Jia Nee Foo, M B Melo, Wing Lau Ho, Ahmad Tajudin Liza-Sharmini, Alex W. Hewitt, Mary Ann T Catacutan, Carlo Lavia, Curt Hartleben-Matkin, Hon-Tym Wong, Daniela Paoli, Srinivasan Kavitha, Su Nyunt Zaw, Soon Thye Lim, Owen Hee, Yee Yee Aung, Shuang Ru Goh, Chiea Chuen Khor, Maria Cecilia Aquino, Jonathan C.H. Chan, Buddha Basnyat, Zeiras Eka Djamal, Nhu Hon Do, Tuyet Bach Trinh, John H. Fingert, Z. Xie, Thi Lam Huong Dao, Urszula Lukasik, Bruno Batista de Souza, Khaled K. Abu-Amero, Yoko Ikeda, Guillermo Barreto Fong, Eng Hui Gan, Guangxian Tang, Sami Al-Shahwan, Tien Dat Tran, Jost B. Jonas, Xiao Yin Chen, Nagaswamy Soumittra, David Goh, Ramanjit Sihota, Xiao-Yu Ng, Ki Ho Park, Mona S Awadalla, Sujie Fan, Edgar U Leuenberger, Hlaing May Than, Jimmy S. M. Lai, Yi Xin Zeng, Shamira A. Perera, Bonnie Nga Kwan Choy, Jie Jin Wang, Roopam Duvesh, Antonio Maria Fea, Anita Manassakorn, Victor H. K. Yong, Abhilasha Karkey, John F Salmon, Kessara Pathanapitoon, Raheel Qamar, Juan Carlos Zenteno, Jin Wook Jeoung, Jovell Ian M Peregrino, Harm Snippe, Yaakub Azhany, Humaira Ayub, Vania Castro Tamanaja, Paolo Frezzotti, Tung S Hoan, Rajesh S. Kumar, Chelvin C A Sng, Jamie E Craig, Anuwat Prutthipongsit, Vital Paulino Costa, Subbiah. R. Krishnadas, Kuldeep Mohanty, Michael A. Hauser, Vi Huyen Doan, Irene R Felarca, Lingam Vijaya, Jennifer W. H. Shum, Farah Akhtar, R. Rand Allingham, Nuttamon Srisamran, Desmond Quek, Huaizhou Wang, Thipnapa Patthanathamrongkasem, Giulia Pignata, Suman S Thapa, Kazuhiko Mori, Jamil Miguel Neto, Tien Yin Wong, Boon-Ang Lim, Zheng Li, Genome Institute of Singapore (GIS), National University of Singapore (NUS), Vietnam National Institute of Ophthalmology (VNIO), Beijing Tongren Hospital, Kyoto University [Kyoto], Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], This research is supported by the Singapore Ministry of Health's National Medical Research Council under its Translational and Clinical Research (TCR) Flagship Programme Grant Stratified Medicine for Primary Angle Closure Glaucoma (NMRC/TCR/008-SERI/2013) and the Singapore Translational Research (STaR) Investigator Award Singapore Angle Closure Glaucoma Program Characterization, Prevention, and Management (NMRC/STAR/0023/2014), as well as the Biomedical Research Council, Agency for Science, Technology and Research (A-STAR), Singapore. A.T.L.-S. gratefully acknowledges support from grants RUI 1001/PPSP/812101 and RUI 1001/PPSP/812152 from the Universiti Sains Malaysia. H.J., C.Q., and N. Wang acknowledge support from the Program of Beijing Scholars (2013), Leading Talents–High-Level Talents of the Health System of Beijing (2009-1-05), and the National Major Scientific and Technological Special Project for 'Significant New Drugs Development' (2011ZX09302-007-05), as well as Project of the National Natural Science Foundation of China (81570837) grants., Kyoto University, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, MESH: Gene Expression, Genotype, Population, Gene Expression, Glaucoma, Genome-wide association study, Biology, Primary angle-closure glaucoma, MESH: Genetic Loci, Cell Line, MESH: Genotype, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Humans, SNP, Genetic Predisposition to Disease, education, education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Genetic Predisposition to Disease, Chromosome Mapping, Odds ratio, medicine.disease, MESH: Male, 3. Good health, MESH: Cell Line, 030104 developmental biology, Genetic Loci, MESH: Genome-Wide Association Study, 030221 ophthalmology & optometry, Susceptibility locus, MESH: Glaucoma, Angle-Closure, Female, Glaucoma, Angle-Closure, MESH: Chromosome Mapping, MESH: Female, Genome-Wide Association Study
Abstract

International audience; Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

Published
2016
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13. Polymorphisms in SP110 are not associated with pulmonary tuberculosis in Indonesians

Author

Mark Seielstad, Sangkot Marzuki, Ron Nelwan, Eileen Png, Bachti Alisjahbana, Reinout van Crevel, Martin L. Hibberd, Esther van de Vosse, Edhyana Sahiratmadja, Iskandar Adnan, and Tom H. M. Ottenhoff

Subjects
Microbiology (medical), Tuberculosis, Genotype, Genome-wide association study, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Microbiology, SP110, Cohort Studies, Minor Histocompatibility Antigens, Mycobacterium tuberculosis, Pulmonary tuberculosis, medicine, Genetics, Humans, SNP, Genetic Predisposition to Disease, Tuberculosis, Pulmonary, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Chi-Square Distribution, biology, Poverty-related infectious diseases [N4i 3], Nuclear Proteins, Case-control, biology.organism_classification, medicine.disease, Infectious Diseases, Susceptibility, Indonesia, Case-Control Studies, Cohort, Immunology, Infection severity, Poverty-related infectious diseases Infectious diseases and international health [N4i 3]
Abstract

Item does not contain fulltext Despite being high transmissible, Mycobacterium tuberculosis (M. tuberculosis) infection causes active disease in only 5-10% of disease-susceptible individuals. This has instigated interest in studying potentially underlying genetic host factors and mechanisms in tuberculosis (TB). The recent identification of the Intracellular pathogen resistance 1 (Ipr1) gene, which plays a major role in controlling M. tuberculosis susceptibility and infection severity in mice (Pan et al., 2005), has prompted studies on its human homolog; SP110 in humans. Association of SP110 SNPs with pulmonary TB were first reported in a study on West African families (Tosh et al., 2006). Subsequent attempts to replicate these findings in other populations, including another West African (Ghanaian) cohort (Thye et al., 2006), however, were unsuccessful. Here we have genotyped 20 SNPs located in the SP110 gene, including the previously TB associated variants; rs2114592 and rs3948464, for the first time in a South East Asian cohort from Indonesia. Our study did not reveal any statistically significant associations between SP110 SNPs and pulmonary TB. In addition, a meta-analysis of the two previously TB associated SNPs revealed that these are not associated with TB, further confirming the lack of convincing evidence for SP110 to be implicated in TB susceptibility, as yet in humans. 01 augustus 2012

Published
2012

14. A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region

Author

Mark Seielstad, Greet J. Boland, Rick T.H. Ong, Harm Snippe, Anbupalam Thalamuthu, and Eileen Png

Subjects
Hepatitis B vaccine, Population, Genome-wide association study, Human leukocyte antigen, Biology, Polymorphism, Single Nucleotide, Virus, Hepatitis B, Chronic, Asian People, HLA Antigens, Genetics, medicine, Humans, Hepatitis B Vaccines, Hepatitis Antibodies, education, Molecular Biology, Genetics (clinical), education.field_of_study, Antibody titer, General Medicine, Odds ratio, Hepatitis B, medicine.disease, Virology, Indonesia, Case-Control Studies, Immunology, Genome-Wide Association Study
Abstract

We performed a two-stage genome-wide association study (GWAS) of antibody titer in 3614 hepatitis B vaccine recipients from Indonesia’s Riau Archipelago, leading to the identification of at least three independent signals within the human leukocyte antigen (HLA) complex. These appear to implicate HLA-DR [rs3135363; P 5 6.53 3 10 222 ; odds ratio (OR) 5 1.53, 95% confidence interval (CI) 5 1.35 –1 .74]; HLA-DP, previously associated with the risk of chronic hepatitis B infection (rs9277535; P 5 2.91 3 10 212 ;O R5 0.72, 95% CI 5 0.63–0.81); and a gene rich HLA Class III interval (rs9267665; P 5 1.24 3 10 217 ;O R5 2.05, CI 5 1.64–2.57). The substantial overlap of these variants and those identified by GWAS of chronic hepatitis B infection confirms vaccine response as a model for infection, while suggesting that the vaccine is least effective in those most at risk of lifelong infection, following exposure to the virus.

Published
2011
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15. Mapping Human Genetic Diversity in Asia

Author

Kiran Kumar Mandapati, Wei Huang, Akira Oka, Hidetoshi Inoko, Kristina A. Tabbada, Jazelyn M. Salvador, Vinod Scaria, Takashi Gojobori, Frederick C. Delfin, Kuchan Kimm, Bermseok Oh, Mitali Mukerji, Sumio Sugano, Sangsoo Kim, Ying Wang, Katsushi Tokunaga, Amit Sinha, Jieming Chen, Jer-Yuarn Wu, Mohd Ros Sidek, Junsong Han, Norio Niikawa, Tomohiro Koike, Mark Seielstad, Yoshiyuki Suzuki, Yuan-Tsong Chen, Samir K. Brahmachari, Huasheng Xiao, Edison T. Liu, Haifeng Wang, Daoroong Kangwanpong, Bin Alwi Zilfalil, Hyang Sook Yoo, Yuliana Sandraling, Jong-Young Lee, Sunghoon Lee, Jatupol Kampuansai, Helena Suryadi, Nao Nishida, Yin Yao Shugart, Eric Wang, Herawati Sudoyo, Jun Ohashi, Ho Ghang, Carmencita Padilla, Eva Maria Cutiongco-de la Paz, Ikhlak Ahmed, Sangho Oh, Suthat Fuchareon, Maude E. Phipps, Sangkot Marzuki, Metawee Srikummool, Boon Peng Hoh, Preeti Khurana, Lilian P. Villamor, Chumpol Ngamphiw, Chien-Hsiun Chen, Pankaj Jha, Maria Corazon A. De Ungria, Li Jin, Gayvelline C. Calacal, Yoshiyuki Sakaki, Henry B. Perdigon, Rick Twee-Hee Ong, Prasit Palittapongarnpim, Adrian Tan, Wentao Yuan, Jong Bhak, Vikrant Kumar, Anunchai Assawamakin, Jongsun Jung, Kwangjoong Kim, Hyung Lae Kim, Ryosuke Kimura, Jiayou Chu, Sissades Tongsima, Juli Edo, Poh San Lai, Woo Yeon Kim, Wayne Mitchell, Guoping Zhao, Giulia C. Kennedy, Shuhua Xu, Partha P. Majumder, Mahmood Ameen Abdulla, Jin Ok Yang, Amit Kumar Chaurasia, Eileen Png, Timothy A. Jinam, Sheng Feng Ho, Supasak Kulawonganunchai, and Kenji Naritomi

Subjects
Gene Flow, Asia, Genotype, media_common.quotation_subject, Genetic genealogy, Human genetic variation, Southeast asian, Polymorphism, Single Nucleotide, Gene flow, Asian People, Genetic variation, Ethnicity, Cluster Analysis, Humans, East Asia, History, Ancient, Phylogeny, Language, Oligonucleotide Array Sequence Analysis, media_common, Genetics, Principal Component Analysis, Multidisciplinary, Geography, Haplotype, Bayes Theorem, Linguistics, Emigration and Immigration, Haplotypes, Evolutionary biology, Algorithms, Diversity (politics)
Abstract

Patterns of Early Migration In order to gain insight into various migrations that must have happened during movement of early humans into Asia and the subsequent populating of the largest continent on Earth, the HUGO Pan-Asian SNP Consortium (p. 1541 ) analyzed genetic variation in almost 2000 individuals representing 73 Asian and two non-Asian populations. The results suggest that there may have been a single major migration of people into Asia and a subsequent south-to-north migration across the continent. While most populations from the same linguistic group tend to cluster together in terms of relatedness, several do not, clustering instead with their geographic neighbors, suggesting either substantial recent mixing among the populations or language replacement. Furthermore, data from indigenous Taiwanese populations appear to be inconsistent with the idea of a Taiwan homeland for Austronesian populations.

Published
2009
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16. Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies

Author

Federico Martinón-Torres, Ana Vega, J I Muñoz Bonet, Á Ortega, J López-Bayón, Sara Pischedda, Martin L. Hibberd, M C León León, A B Arriortua, C P Caballero Macarrón, M L Millán Miralles, Victoria J. Wright, Simon Nadel, Kar Seng Sim, E E Torné, Nazareth Martinón-Torres, García, A H Doce, F G Sánchez, Ruth Barral-Arca, Dominguez, R Payo, F P Sánchez, J M Sánchez Granados, Carmen Rodríguez-Tenreiro, E Morteruel, M S Cancela, Á Barba, N G Sánchez, M. J. Curras-Tuala, Jacobo Pardo-Seco, E O Bergara, M L Navarro Gómez, David Inwald, S P Rosso, Sergio Alonso, Marcela Fernández, Garzón Mgr., A R Romero, J De La Cruz Moreno, Antonio Salas, García Mdmb., A J Grande, C C Monge, A C Torre, Enitan D. Carrol, S C Palazón, Laura Fachal, N M Menchón, J L García Rodríguez, M O Pallares, Michael Levin, Sonia Davila, O S Ayestarán, Alberto Gómez-Carballa, Chiea Chuen Khor, Irene Rivero Calle, Miriam Cebey, De Aguilar Pag., Eileen Png, Angel Carracedo, José María Martinón-Sánchez, Xavier Martinez, Martínez-Padilla Mdc., Lorenzo Redondo-Collazo, Fachal Vilar, Laura [0000-0002-7256-9752], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Databases, Factual, Genotype, Single-nucleotide polymorphism, Genome-wide association study, Disease, Meningococcal disease, Polymorphism, Single Nucleotide, White People, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Odds Ratio, Missense mutation, SNP, Humans, genetics, 030212 general & internal medicine, Genetics, Multidisciplinary, business.industry, Odds ratio, medicine.disease, Immunity, Innate, 3. Good health, Meningococcal Infections, 030104 developmental biology, Genetic Loci, Spain, Meta-analysis, Complement Factor H, genetic association study, business, Genome-Wide Association Study
Abstract

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10−8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52–0.73; P-value = 9.62 × 10−9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55–0.76, P-value = 3.25 × 10−8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

Published
2016
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17. Abstract O.16: Comprehensive Genotyping Of The FCGR2/3 Locus Reveals A Novel Association Of FCGR2C-ORF With Susceptibility To Kawasaki Disease

Author

Taco W Kuijpers, Carline E Tacke, Sietse Q Nagelkerke, Willemijn B Breunis, Long T Hoang, Eileen Png, Judy Geissler, Michael W Tanck, Justine A Ellis, Anne L Ponsonby, Sonia Davila, Chiea C Khor, Martin de Boer, Joris van der Heijden, Karin Fijnvandraat, E. van der Schoot, Timo K van den Berg, Rae S Yeung, Michael L Levin, David Burgner, Chisato Shimizu, Jane C Burns, and Martin L Hibberd

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

The human FCGR2/3 locus contains highly homologous genes encoding the five major receptors for IgG (Fc-gamma receptors, FcγRs). In two prior GWAS on Kawasaki disease (KD), a SNP in FCGR2A (131H>R; rs1801274) was identified to be associated with disease susceptibility. However, the FCGR2/3 locus contains multiple single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), which were not covered by the detection platforms used in the GWAS. In this study we therefore focused on further fine-mapping of this locus to investigate the association of the different genetic variations with KD susceptibility. A highly accurate and validated multiplex ligation-dependent probe amplification (MLPA) assay was used to analyze all functionally relevant SNPs and CNVs within this locus. In a genetic association study involving case-control and family-based testing with 1028 patients with KD, the previous finding of FCGR2A-131H as a susceptibility marker for KD was confirmed (OR 1.16; 95%CI 1.08-1.32, meta-P = 0.01). In addition, we found a novel significant association of the FCGR2C-ORF haplotype with susceptibility to KD (OR 1.34; 95% confidence interval 1.11-1.62, meta-P = 0.003). FCGR2C-ORF leads to the expression of an extra, functionally activating FcγR (i.e. FcγRIIc) on myeloid cell types and NK cells. Being absent in Asian individuals, the FCGR2C-ORF haplotype only contributed to KD susceptibility in European subjects, independent of the established association with FCGR2A-H131R. We did not find any significant association of CNV of the locus with susceptibility to KD. Our data point to an important role of the activating FcγRs in KD pathology. We hypothesize that the identified functional SNPs might alter the balance between the activating and inhibitory FcγRs leading to unbalanced inflammation and KD.

Published
2015
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18. Sensitive detection of chromatin-altering polymorphisms reveals autoimmune disease mechanisms

Author

Eileen Png, Chiea Chuen Khor, Jeremie Poschmann, Martin L. Hibberd, Sigrid L. Rouam, Shyam Prabhakar, Ricardo C.H. del Rosario, Le Bihan, Sylvie, Genome Institute of Singapore (GIS), National University of Singapore (NUS), Singapore Eye Research Institute [Singapore] (SERI), and London School of Hygiene and Tropical Medicine (LSHTM)

Subjects
Genetic Markers, Genotype, [SDV]Life Sciences [q-bio], Quantitative Trait Loci, Genome-wide association study, Biology, Quantitative trait locus, Biochemistry, Polymorphism, Single Nucleotide, Cell Line, Histones, Humans, Molecular Biology, Genotyping, Alleles, Genetic association, Genetics, Regulation of gene expression, Acetylation, Cell Biology, Chromatin, [SDV] Life Sciences [q-bio], Histone, Gene Expression Regulation, Allelic Imbalance, biology.protein, Transcriptome, Biotechnology
Abstract

International audience; Most disease associations detected by genome-wide association studies (GWAS) lie outside coding genes, but very few have been mapped to causal regulatory variants. Here, we present a method for detecting regulatory quantitative trait loci (QTLs) that does not require genotyping or whole-genome sequencing. The method combines deep, long-read chromatin immunoprecipitation–sequencing (ChIP-seq) with a statistical test that simultaneously scores peak height correlation and allelic imbalance: the genotype-independent signal correlation and imbalance (G-SCI) test. We performed histone acetylation ChIP-seq on 57 human lymphoblastoid cell lines and used the resulting reads to call 500,066 single-nucleotide polymorphisms de novo within regulatory elements. The G-SCI test annotated 8,764 of these as histone acetylation QTLs (haQTLs)—an order of magnitude larger than the set of candidates detected by expression QTL analysis. Lymphoblastoid haQTLs were highly predictive of autoimmune disease mechanisms. Thus, our method facilitates large-scale regulatory variant detection in any moderately sized cohort for which functional profiling data can be generated, thereby simplifying identification of causal variants within GWAS loci.

Published
2015
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19. A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

Author

Edhyana Sahiratmadja, Esther van de Vosse, Mark Seielstad, Vladyslav Nikolayevskyy, Iskandar Adnan, Tom H. M. Ottenhoff, Eileen Png, Francis Drobniewski, Sergey Nejentsev, Ron Nelwan, Sangkot Marzuki, Reinout van Crevel, Yanina Balabanova, Bachti Alisjahbana, Martin L. Hibberd, Nezhentsev, Sergey [0000-0002-7528-4461], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, lcsh:Internal medicine, lcsh:QH426-470, Adolescent, Genotype, Genome-wide association study, Single-nucleotide polymorphism, Biology, Southeast asian, Polymorphism, Single Nucleotide, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Genetics, Humans, SNP, Genetic Predisposition to Disease, Genetics(clinical), lcsh:RC31-1245, Tuberculosis, Pulmonary, Genetics (clinical), Aged, 030304 developmental biology, Genetic association, Aged, 80 and over, 0303 health sciences, Genome, Human, Poverty-related infectious diseases [N4i 3], Middle Aged, 3. Good health, lcsh:Genetics, Phenotype, Indonesia, 030220 oncology & carcinogenesis, Cohort, Female, Poverty-related infectious diseases Infectious diseases and international health [N4i 3], Research Article, Genome-Wide Association Study, Cohort study
Abstract

Background There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia. Methods In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia. Results Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4. Conclusions Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.

Published
2012
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20. Genetic determinants of hepatitis B vaccine response

Author

Eileen Png, Greet J. Boland, Rick Th Ong, Harm Snippe, Mark Seielstad, David H. Muljono, Herawati Sudoyo, Anbupalam Thalamuthu, and Sangkot Marzuki

Subjects
0106 biological sciences, Hepatitis B vaccine, Population, Genome-wide association study, medicine.disease_cause, Chronic liver disease, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, medicine, education, Hepatitis B virus, education.field_of_study, business.industry, 04 agricultural and veterinary sciences, General Medicine, Hepatitis B, medicine.disease, Vaccine efficacy, Virology, 3. Good health, Vaccination, Immunology, 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Oral Presentation, business, 010606 plant biology & botany
Abstract

Hepatitis B is a major public health problem. Approximately one-third of the world’s population has serological evidence of infection with hepatitis B virus (HBV). 350 million of these are carriers who have chronic HBV infection, and about a million of these carriers die each year from chronic liver disease, including cirrhosis and liver cancer. Fortunately, HBV is a vaccine preventable disease, and the increasing adoption of this vaccine has led to dramatic reductions in the morbidity and mortality caused by this virus. However, as much as 10% of the population fails to mount a protective immune response after vaccination. Twin and other epidemiological studies have demonstrated an unusually high heritability to this trait, which suggests a high likelihood of identifying genetic variation influencing HBV vaccine response. In search of such variation, we performed a two stage Genome Wide Association Scan (GWAS) in participants of a vaccine efficacy trial from Batam, Indonesia. In Stage 1, we used the fixed content Illumina Infinium 550K SNP BeadChip to genotype 2000 vaccinees. Tests of association were performed to identify 7,000 SNPs to carry forward to a second stage of 2,300 vaccinees. Several independent regions attained genome-wide significance, including the HLA-DR and HLA-DP regions. Additional details on the study design and results will be discussed in the presentation.

Published
2011

21. Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment

Author

Chng K. R., Li C., Bertrand D., Ng A. H. Q., Kwah J. S., Low H. M., Tong C., Natrajan M., Zhang M. H., Xu L., Ko K. K. K., Ho E. X. P., Av-Shalom T. V., Teo J. W. P., Khor C. C., Danko D., Bezdan D., Afshinnekoo E., Ahsanuddin S., Bhattacharya C., Butler D. J., De Filippis F., Hecht J., Kahles A., Karasikov M., Kyrpides N. C., Leung M. H. Y., Meleshko D., Mustafa H., Mutai B., Neches R. Y., Ng A., Nieto-Caballero M., Nikolayeva O., Nikolayeva T., Png E., Sanchez J. L., Shaaban H., Sierra M. A., Tong X., Young B., Alicea J., Bhattacharyya M., Blekhman R., Castro-Nallar E., Canas A. M., Chatziefthimiou A. D., Crawford R. W., Deng Y., Desnues C., Dias-Neto E., Donnellan D., Dybwad M., Elhaik E., Ercolini D., Frolova A., Graf A. B., Green D. C., Hajirasouliha I., Hernandez M., Iraola G., Jang S., Jones A., Kelly F. J., Knights K., Labaj P. P., Lee P. K. H., Shawn L., Ljungdahl P., Lyons A., Mason-Buck G., McGrath K., Mongodin E. F., Moraes M. O., Nagarajan N., Noushmehr H., Oliveira M., Ossowski S., Osuolale O. O., Ozcan O., Paez-Espino D., Rascovan N., Richard H., Ratsch G., Schriml L. M., Semmler T., Sezerman O. U., Shi L., Song L. H., Suzuki H., Court D. S., Thomas D., Tighe S. W., Udekwu K. I., Ugalde J. A., Valentine B., Vassilev D. I., Vayndorf E., Velavan T. P., Zambrano M. M., Zhu J., Zhu S., Mason C. E., Chen S. L., Ng O. T., Marimuthu K., Ang B., Genome Institute of Singapore (GIS), Singapore University of Technology and Design (SUTD), Singapore General Hospital, National University Hospital [Singapore] (NUH), Weill Cornell Medicine [Cornell University], Cornell University [New York], Nanyang Technological University [Singapour], Tan Tock Seng Hospital, Department of Computational and Systems Biology [Singapore], Funding for this work was provided by A*STAR (N.N.), and we are grateful for support from NMRC (NMRC CGAug16C005: O.T.N. and K.M.). C.E.M. acknowledges support from the WorldQuant Foundation, the Bill and Melinda Gates Foundation (OPP1151054) and the Alfred P. Sloan Foundation (G-2015-13964). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. We would like to thank J. Gilbert for insightful comments and feedback on this work., MetaSUB Consortium: David Danko, Daniela Bezdan, Ebrahim Afshinnekoo, Sofia Ahsanuddin, Chandrima Bhattacharya, Daniel J. Butler, Kern Rei Chng, Francesca De Filippis, Jochen Hecht, Andre Kahles, Mikhail Karasikov, Nikos C. Kyrpides, Marcus H. Y. Leung, Dmitry Meleshko, Harun Mustafa, Beth Mutai, Russell Y. Neches, Amanda Ng, Marina Nieto-Caballero, Olga Nikolayeva, Tatyana Nikolayeva, Eileen Png, Jorge L. Sanchez, Heba Shaaban, Maria A. Sierra, Xinzhao Tong, Ben Young, Josue Alicea, Malay Bhattacharyya, Ran Blekhman, Eduardo Castro-Nallar, Ana M. Cañas, Aspassia D. Chatziefthimiou, Robert W. Crawford, Youping Deng, Christelle Desnues, Emmanuel Dias-Neto, Daisy Donnellan, Marius Dybwad, Eran Elhaik, Danilo Ercolini, Alina Frolova, Alexandra B. Graf, David C. Green, Iman Hajirasouliha, Mark Hernandez, Gregorio Iraola, Soojin Jang, Angela Jones, Frank J. Kelly, Kaymisha Knights, Paweł P. Łabaj, Patrick K. H. Lee, Levy Shawn, Per Ljungdahl, Abigail Lyons, Gabriella Mason-Buck, Ken McGrath, Emmanuel F. Mongodin, Milton Ozorio Moraes, Niranjan Nagarajan, Houtan Noushmehr, Manuela Oliveira, Stephan Ossowski, Olayinka O. Osuolale, Orhan Özcan, David Paez-Espino, Nicolas Rascovan, Hugues Richard, Gunnar Rätsch, Lynn M. Schriml, Torsten Semmler, Osman U. Sezerman, Leming Shi, Le Huu Song, Haruo Suzuki, Denise Syndercombe Court, Dominique Thomas, Scott W. Tighe, Klas I. Udekwu, Juan A. Ugalde, Brandon Valentine, Dimitar I. Vassilev, Elena Vayndorf, Thirumalaisamy P. Velavan, María M. Zambrano, Jifeng Zhu, Sibo Zhu & Christopher E. Mason, Weill Cornell Medicine [New York], Chng, K. R., Li, C., Bertrand, D., Ng, A. H. Q., Kwah, J. S., Low, H. M., Tong, C., Natrajan, M., Zhang, M. H., Xu, L., Ko, K. K. K., Ho, E. X. P., Av-Shalom, T. V., Teo, J. W. P., Khor, C. C., Danko, D., Bezdan, D., Afshinnekoo, E., Ahsanuddin, S., Bhattacharya, C., Butler, D. J., De Filippis, F., Hecht, J., Kahles, A., Karasikov, M., Kyrpides, N. C., Leung, M. H. Y., Meleshko, D., Mustafa, H., Mutai, B., Neches, R. Y., Ng, A., Nieto-Caballero, M., Nikolayeva, O., Nikolayeva, T., Png, E., Sanchez, J. L., Shaaban, H., Sierra, M. A., Tong, X., Young, B., Alicea, J., Bhattacharyya, M., Blekhman, R., Castro-Nallar, E., Canas, A. M., Chatziefthimiou, A. D., Crawford, R. W., Deng, Y., Desnues, C., Dias-Neto, E., Donnellan, D., Dybwad, M., Elhaik, E., Ercolini, D., Frolova, A., Graf, A. B., Green, D. C., Hajirasouliha, I., Hernandez, M., Iraola, G., Jang, S., Jones, A., Kelly, F. J., Knights, K., Labaj, P. P., Lee, P. K. H., Shawn, L., Ljungdahl, P., Lyons, A., Mason-Buck, G., Mcgrath, K., Mongodin, E. F., Moraes, M. O., Nagarajan, N., Noushmehr, H., Oliveira, M., Ossowski, S., Osuolale, O. O., Ozcan, O., Paez-Espino, D., Rascovan, N., Richard, H., Ratsch, G., Schriml, L. M., Semmler, T., Sezerman, O. U., Shi, L., Song, L. H., Suzuki, H., Court, D. S., Thomas, D., Tighe, S. W., Udekwu, K. I., Ugalde, J. A., Valentine, B., Vassilev, D. I., Vayndorf, E., Velavan, T. P., Zambrano, M. M., Zhu, J., Zhu, S., Mason, C. E., Chen, S. L., Ng, O. T., Marimuthu, K., Ang, B., and Acibadem University Dspace

Subjects
0301 basic medicine, Disease prevention, 030106 microbiology, Geographic Mapping, Drug resistance, Beds, Biology, Opportunistic Infections, Genome, General Biochemistry, Genetics and Molecular Biology, Article, Tertiary Care Centers, 03 medical and health sciences, Plasmid, Antibiotic resistance, Spatio-Temporal Analysis, Drug Resistance, Multiple, Bacterial, Drug Resistance, Bacterial, Patients' Rooms, Humans, Microbiome, Equipment and Supplies, Hospital, Genetics, Cross Infection, Infection Control, Singapore, Microbiota, General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Resistome, Disinfection, 030104 developmental biology, Metagenomics, Biofilms, Equipment Contamination, Mobilome, Microbial genetics
Abstract

Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections., Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.

Published
2020
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