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

Author

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

Published
2024
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4. A global metagenomic map of urban microbiomes and antimicrobial resistance.

Author

Danko, David, Bezdan, Daniela, Afshin, Evan E, Ahsanuddin, Sofia, Bhattacharya, Chandrima, Butler, Daniel J, Chng, Kern Rei, Donnellan, Daisy, Hecht, Jochen, Jackson, Katelyn, Kuchin, Katerina, Karasikov, Mikhail, Lyons, Abigail, Mak, Lauren, Meleshko, Dmitry, Mustafa, Harun, Mutai, Beth, Neches, Russell Y, Ng, Amanda, Nikolayeva, Olga, Nikolayeva, Tatyana, Png, Eileen, Ryon, Krista A, Sanchez, Jorge L, Shaaban, Heba, Sierra, Maria A, Thomas, Dominique, Young, Ben, Abudayyeh, Omar O, Alicea, Josue, Bhattacharyya, Malay, Blekhman, Ran, Castro-Nallar, Eduardo, Cañas, Ana M, Chatziefthimiou, Aspassia D, Crawford, Robert W, De Filippis, Francesca, Deng, Youping, Desnues, Christelle, Dias-Neto, Emmanuel, Dybwad, Marius, Elhaik, Eran, Ercolini, Danilo, Frolova, Alina, Gankin, Dennis, Gootenberg, Jonathan S, Graf, Alexandra B, Green, David C, Hajirasouliha, Iman, Hastings, Jaden JA, Hernandez, Mark, Iraola, Gregorio, Jang, Soojin, Kahles, Andre, Kelly, Frank J, Knights, Kaymisha, Kyrpides, Nikos C, Łabaj, Paweł P, Lee, Patrick KH, Leung, Marcus HY, Ljungdahl, Per O, Mason-Buck, Gabriella, McGrath, Ken, Meydan, Cem, Mongodin, Emmanuel F, Moraes, Milton Ozorio, Nagarajan, Niranjan, Nieto-Caballero, Marina, Noushmehr, Houtan, Oliveira, Manuela, Ossowski, Stephan, Osuolale, Olayinka O, Özcan, Orhan, Paez-Espino, David, Rascovan, Nicolás, Richard, Hugues, Rätsch, Gunnar, Schriml, Lynn M, Semmler, Torsten, Sezerman, Osman U, Shi, Leming, Shi, Tieliu, Siam, Rania, Song, Le Huu, Suzuki, Haruo, Court, Denise Syndercombe, Tighe, Scott W, Tong, Xinzhao, Udekwu, Klas I, Ugalde, Juan A, Valentine, Brandon, Vassilev, Dimitar I, Vayndorf, Elena M, Velavan, Thirumalaisamy P, Wu, Jun, Zambrano, María M, Zhu, Jifeng, Zhu, Sibo, Mason, Christopher E, and International MetaSUB Consortium

Subjects
International MetaSUB Consortium, AMR, BGC, NGS, antimicrobial resistance, built Environment, de novo assembly, global health, metagenome, microbiome, shotgun sequencing, Antimicrobial Resistance, Biotechnology, Human Genome, Genetics, Infection, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

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.

Published
2021

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

Author

Chng, Kern Rei, Li, Chenhao, Bertrand, Denis, Ng, Amanda Hui Qi, Kwah, Junmei Samantha, Low, Hwee Meng, Tong, Chengxuan, Natrajan, Maanasa, Zhang, Michael Hongjie, Xu, Licheng, Ko, Karrie Kwan Ki, Ho, Eliza Xin Pei, Av-Shalom, Tamar V, Teo, Jeanette Woon Pei, Khor, Chiea Chuen, MetaSUB Consortium, Chen, Swaine L, Mason, Christopher E, Ng, Oon Tek, Marimuthu, Kalisvar, Ang, Brenda, and Nagarajan, Niranjan

Subjects
MetaSUB Consortium, Humans, Biofilms, Cross Infection, Opportunistic Infections, Equipment and Supplies, Hospital, Beds, Equipment Contamination, Infection Control, Disinfection, Drug Resistance, Bacterial, Drug Resistance, Multiple, Bacterial, Patients' Rooms, Singapore, Metagenomics, Tertiary Care Centers, Spatio-Temporal Analysis, Geographic Mapping, Microbiota, Medical and Health Sciences, Immunology
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.

Published
2020

9. A global metagenomic map of urban microbiomes and antimicrobial resistance

Author

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

Published
2021
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10. Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity

Author

Tay, Angeline S.L., Li, Chenhao, Nandi, Tannistha, Chng, Kern Rei, Andiappan, Anand Kumar, Mettu, Vijaya Saradhi, de Cevins, Camille, Ravikrishnan, Aarthi, Dutertre, Charles-Antoine, Wong, X.F. Colin C., Ng, Amanda Hui Qi, Matta, Sri Anusha, Ginhoux, Florent, Rötzschke, Olaf, Chew, Fook Tim, Tang, Mark B.Y., Yew, Yik Weng, Nagarajan, Niranjan, and Common, John E.A.

Published
2021
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14. Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma

Author

Chng, Kern Rei, Chan, Sock Hoai, Ng, Amanda Hui Qi, Li, Chenhao, Jusakul, Apinya, Bertrand, Denis, Wilm, Andreas, Choo, Su Pin, Tan, Damien Meng Yew, Lim, Kiat Hon, Soetinko, Roy, Ong, Choon Kiat, Duda, Dan G., Dima, Simona, Popescu, Irinel, Wongkham, Chaisiri, Feng, Zhu, Yeoh, Khay Guan, Teh, Bin Tean, Yongvanit, Puangrat, Wongkham, Sopit, Bhudhisawasdi, Vajaraphongsa, Khuntikeo, Narong, Tan, Patrick, Pairojkul, Chawalit, Ngeow, Joanne, and Nagarajan, Niranjan

Published
2016
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16. Enhanced triacylglycerol catabolism by carboxylesterase 1 promotes aggressive colorectal carcinoma

Author

Capece, Daria, DAndrea, Daniel, Begalli, Federica, Goracci, Laura, Tornatore, Laura, Alexander, James L., Veroli, Alessandra Di, Leow, Shi-Chi, Vaiyapuri, Thamil S., Ellis, James K., Verzella, Daniela, Bennett, Jason, Savino, Luca, Ma, Yue, McKenzie, James S., Doria, Maria Luisa, Mason, Sam E., Chng, Kern Rei, Keun, Hector C., Frost, Gary, Tergaonkar, Vinay, Broniowska, Katarzyna, Stunkel, Walter, Takats, Zoltan, Kinross, James M., Cruciani, Gabriele, and Franzoso, Guido

Subjects
Physiological aspects, Development and progression, Genetic aspects, Health aspects, Esterases -- Genetic aspects -- Health aspects, Lipolysis -- Health aspects -- Genetic aspects, Catabolism -- Health aspects, Colorectal cancer -- Development and progression -- Genetic aspects, Triglycerides -- Physiological aspects -- Health aspects
Abstract

Introduction Tumor cells must adapt to the low nutrient concentrations in the tumor microenvironment (TME) in order to survive, proliferate, and spread to distant sites (1-4). The availability of nutrients, [...], The ability to adapt to low-nutrient microenvironments is essential for tumor cell survival and progression in solid cancers, such as colorectal carcinoma (CRC). Signaling by the NF-[kappa]B transcription factor pathway associates with advanced disease stages and shorter survival in patients with CRC. NF-[kappa]B has been shown to drive tumor-promoting inflammation, cancer cell survival, and intestinal epithelial cell (IEC) dedifferentiation in mouse models of CRC. However, whether NF-[kappa]B affects the metabolic adaptations that fuel aggressive disease in patients with CRC is unknown. Here, we identified carboxylesterase 1 (CES1) as an essential NF-[kappa]B-regulated lipase linking obesity-associated inflammation with fat metabolism and adaptation to energy stress in aggressive CRC. CES1 promoted CRC cell survival via cell-autonomous mechanisms that fuel fatty acid oxidation (FAO) and prevent the toxic build-up of triacylglycerols. We found that elevated CES1 expression correlated with worse outcomes in overweight patients with CRC. Accordingly, NF-[kappa]B drove CES1 expression in CRC consensus molecular subtype 4 (CMS4), which is associated with obesity, stemness, and inflammation. CES1 was also upregulated by gene amplifications of its transcriptional regulator HNF4A in CMS2 tumors, reinforcing its clinical relevance as a driver of CRC. This subtype-based distribution and unfavorable prognostic correlation distinguished CES1 from other intracellular triacylglycerol lipases and suggest CES1 could provide a route to treat aggressive CRC.

Published
2021
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17. Artificial intelligence and real-world data for drug and food safety - A regulatory science perspective

Author

Thakkar, Shraddha, Slikker, William, Yiannas, Frank, Silva, Primal, Blais, Burton, Chng, Kern Rei, Liu, Zhichao, Adholeya, Alok, Pappalardo, Francesco, Soares, Mônica da Luz Carvalho, Beeler, Patrick E; https://orcid.org/0000-0002-6097-2480, Whelan, Maurice, Roberts, Ruth, Borlak, Jurgen, Hugas, Martha, Torrecilla-Salinas, Carlos, Girard, Philippe, Diamond, Matthew C, Verloo, Didier, Panda, Binay, Rose, Miquella C, Jornet, Joaquim Berenguer, Furuhama, Ayako, Fang, Hong, Kwegyir-Afful, Ernest, Heintz, Kasey, Arvidson, Kirk, Burgos, Juan Garcia, Horst, Alexander, Tong, Weida, Thakkar, Shraddha, Slikker, William, Yiannas, Frank, Silva, Primal, Blais, Burton, Chng, Kern Rei, Liu, Zhichao, Adholeya, Alok, Pappalardo, Francesco, Soares, Mônica da Luz Carvalho, Beeler, Patrick E; https://orcid.org/0000-0002-6097-2480, Whelan, Maurice, Roberts, Ruth, Borlak, Jurgen, Hugas, Martha, Torrecilla-Salinas, Carlos, Girard, Philippe, Diamond, Matthew C, Verloo, Didier, Panda, Binay, Rose, Miquella C, Jornet, Joaquim Berenguer, Furuhama, Ayako, Fang, Hong, Kwegyir-Afful, Ernest, Heintz, Kasey, Arvidson, Kirk, Burgos, Juan Garcia, Horst, Alexander, and Tong, Weida

Abstract

In 2013, the Global Coalition for Regulatory Science Research (GCRSR) was established with members from over ten countries (www.gcrsr.net). One of the main objectives of GCRSR is to facilitate communication among global regulators on the rise of new technologies with regulatory applications through the annual conference Global Summit on Regulatory Science (GSRS). The 11th annual GSRS conference (GSRS21) focused on "Regulatory Sciences for Food/Drug Safety with Real-World Data (RWD) and Artificial Intelligence (AI)." The conference discussed current advancements in both AI and RWD approaches with a specific emphasis on how they impact regulatory sciences and how regulatory agencies across the globe are pursuing the adaptation and oversight of these technologies. There were presentations from Brazil, Canada, India, Italy, Japan, Germany, Switzerland, Singapore, the United Kingdom, and the United States. These presentations highlighted how various agencies are moving forward with these technologies by either improving the agencies' operation and/or preparing regulatory mechanisms to approve the products containing these innovations. To increase the content and discussion, the GSRS21 hosted two debate sessions on the question of "Is Regulatory Science Ready for AI?" and a workshop to showcase the analytical data tools that global regulatory agencies have been using and/or plan to apply to regulatory science. Several key topics were highlighted and discussed during the conference, such as the capabilities of AI and RWD to assist regulatory science policies for drug and food safety, the readiness of AI and data science to provide solutions for regulatory science. Discussions highlighted the need for a constant effort to evaluate emerging technologies for fit-for-purpose regulatory applications. The annual GSRS conferences offer a unique platform to facilitate discussion and collaboration across regulatory agencies, modernizing regulatory approaches, and harmonizing effort

Published
2023

18. Artificial intelligence and real-world data for drug and food safety – A regulatory science perspective

Author

Thakkar, Shraddha, primary, Slikker, William, additional, Yiannas, Frank, additional, Silva, Primal, additional, Blais, Burton, additional, Chng, Kern Rei, additional, Liu, Zhichao, additional, Adholeya, Alok, additional, Pappalardo, Francesco, additional, Soares, Mônica da Luz Carvalho, additional, Beeler, Patrick, additional, Whelan, Maurice, additional, Roberts, Ruth, additional, Borlak, Jurgen, additional, Hugas, Martha, additional, Torrecilla-Salinas, Carlos, additional, Girard, Philippe, additional, Diamond, Matthew C., additional, Verloo, Didier, additional, Panda, Binay, additional, Rose, Miquella C., additional, Jornet, Joaquim Berenguer, additional, Furuhama, Ayako, additional, Fang, Hong, additional, Kwegyir-Afful, Ernest, additional, Heintz, Kasey, additional, Arvidson, Kirk, additional, Burgos, Juan Garcia, additional, Horst, Alexander, additional, and Tong, Weida, additional

Published
2023
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24. Long-term ecological and evolutionary dynamics in the gut microbiomes of carbapenemase-producing Enterobacteriaceae colonized subjects

Author

Jonathan T. L. Kang, Jonathan Teo, Denis Bertrand, Amanda Ng, Aarthi Ravikrishnan, Melvin Yong, Ng Oon Tek, Kalisvar Marimuthu, Swaine Chen, Chng Kern Rei, Gan Yunn-Hwen, and Niranjan Nagarajan

Subjects
Microbiology (medical), Immunology, Cell Biology, Applied Microbiology and Biotechnology, Microbiology, beta-Lactamases, Anti-Bacterial Agents, Gastrointestinal Microbiome, Klebsiella pneumoniae, Carbapenem-Resistant Enterobacteriaceae, Bacterial Proteins, Genetics, Escherichia coli, Humans
Abstract

Long-term colonization of the gut microbiome by carbapenemase-producing Enterobacteriaceae (CPE) is a growing area of public health concern as it can lead to community transmission and rapid increase in cases of life-threatening CPE infections. Here, leveraging the observation that many subjects are decolonized without interventions within a year, we used longitudinal shotgun metagenomics (up to 12 timepoints) for detailed characterization of ecological and evolutionary dynamics in the gut microbiome of a cohort of CPE-colonized subjects and family members (n = 46; 361 samples). Subjects who underwent decolonization exhibited a distinct ecological shift marked by recovery of microbial diversity, key commensals and anti-inflammatory pathways. In addition, colonization was marked by elevated but unstable Enterobacteriaceae abundances, which exhibited distinct strain-level dynamics for different species (Escherichia coli and Klebsiella pneumoniae). Finally, comparative analysis with whole-genome sequencing data from CPE isolates (n = 159) helped identify substrain variation in key functional genes and the presence of highly similar E. coli and K. pneumoniae strains with variable resistance profiles and plasmid sharing. These results provide an enhanced view into how colonization by multi-drug-resistant bacteria associates with altered gut ecology and can enable transfer of resistance genes, even in the absence of overt infection and antibiotic usage.

Published
2022
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30. An AR-ERG transcriptional signature defined by long-range chromatin interactomes in prostate cancer cells

Author

Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Zhang, Zhizhuo, Chng, Kern Rei, Lingadahalli, Shreyas, Chen, Zikai, Liu, Mei Hui, Do, Huy Hoang, Cai, Shaojiang, Rinaldi, Nicola, Poh, Huay Mei, Li, Guoliang, Sung, Ying Ying, Heng, Charlie L., Core, Leighton J., Tan, Si Kee, Ruan, Xiaoan, Lis, John T., Kellis, Manolis, Ruan, Yijun, Sung, Wing-Kin, Cheung, Edwin, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Zhang, Zhizhuo, Chng, Kern Rei, Lingadahalli, Shreyas, Chen, Zikai, Liu, Mei Hui, Do, Huy Hoang, Cai, Shaojiang, Rinaldi, Nicola, Poh, Huay Mei, Li, Guoliang, Sung, Ying Ying, Heng, Charlie L., Core, Leighton J., Tan, Si Kee, Ruan, Xiaoan, Lis, John T., Kellis, Manolis, Ruan, Yijun, Sung, Wing-Kin, and Cheung, Edwin

Abstract

The aberrant activities of transcription factors such as the androgen receptor (AR) underpin prostate cancer development. While the AR cis-regulation has been extensively studied in prostate cancer, information pertaining to the spatial architecture of the AR transcriptional circuitry remains limited. In this paper, we propose a novel framework to profile long-range chromatin interactions associated with AR and its collaborative transcription factor, erythroblast transformation-specific related gene (ERG), using chromatin interaction analysis by paired-end tag (ChIA-PET). We identified ERG-associated long-range chromatin interactions as a cooperative component in the AR-associated chromatin interactome, acting in concert to achieve coordinated regulation of a subset of AR target genes. Through multifaceted functional data analysis, we found that AR-ERG interaction hub regions are characterized by distinct functional signatures, including bidirectional transcription and cotranscription factor binding. In addition, cancer-associated long noncoding RNAs were found to be connected near protein-coding genes through AR-ERG looping. Finally, we found strong enrichment of prostate cancer genome-wide association study (GWAS) single nucleotide polymorphisms (SNPs) at AR-ERG co-binding sites participating in chromatin interactions and gene regulation, suggesting GWAS target genes identified from chromatin looping data provide more biologically relevant findings than using the nearest gene approach. Taken together, our results revealed an ARERG- centric higher-order chromatin structure that drives coordinated gene expression in prostate cancer progression and the identification of potential target genes for therapeutic intervention.

Published
2020

32. An AR-ERG transcriptional signature defined by long-range chromatin interactomes in prostate cancer cells

Author

Zhang, Zhizhuo, primary, Chng, Kern Rei, additional, Lingadahalli, Shreyas, additional, Chen, Zikai, additional, Liu, Mei Hui, additional, Do, Huy Hoang, additional, Cai, Shaojiang, additional, Rinaldi, Nicola, additional, Poh, Huay Mei, additional, Li, Guoliang, additional, Sung, Ying Ying, additional, Heng, Charlie L., additional, Core, Leighton J., additional, Tan, Si Kee, additional, Ruan, Xiaoan, additional, Lis, John T., additional, Kellis, Manolis, additional, Ruan, Yijun, additional, Sung, Wing-Kin, additional, and Cheung, Edwin, additional

Published
2019
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33. Gut microbiome recovery after antibiotic usage is mediated by specific bacterial species

Author

Nandi, Tannistha, primary, Lee, Ivor Russel, additional, Ghosh, Tarini, additional, Qi Ng, Amanda Hui, additional, Chng, Kern Rei, additional, Li, Chenhao, additional, Tan, Yi Han, additional, Lye, David, additional, Barkham, Timothy, additional, Chen, Swaine, additional, Gan, Yunn-Hwen, additional, Young, Barnaby, additional, and Nagarajan, Niranjan, additional

Published
2018
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35. The liver–gut microbiota axis modulates hepatotoxicity of tacrine in the rat

Author

Yip, Lian Yee, primary, Aw, Chiu Cheong, additional, Lee, Sze Han, additional, Hong, Yi Shuen, additional, Ku, Han Chen, additional, Xu, Winston Hecheng, additional, Chan, Jessalyn Mei Xuan, additional, Cheong, Eleanor Jing Yi, additional, Chng, Kern Rei, additional, Ng, Amanda Hui Qi, additional, Nagarajan, Niranjan, additional, Mahendran, Ratha, additional, Lee, Yuan Kun, additional, Browne, Edward R., additional, and Chan, Eric Chun Yong, additional

Published
2017
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37. Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare

Author

Chng, Kern Rei, primary, Tay, Angeline Su Ling, additional, Li, Chenhao, additional, Ng, Amanda Hui Qi, additional, Wang, Jingjing, additional, Suri, Bani Kaur, additional, Matta, Sri Anusha, additional, McGovern, Naomi, additional, Janela, Baptiste, additional, Wong, Xuan Fei Colin C., additional, Sio, Yang Yie, additional, Au, Bijin Veonice, additional, Wilm, Andreas, additional, De Sessions, Paola Florez, additional, Lim, Thiam Chye, additional, Tang, Mark Boon Yang, additional, Ginhoux, Florent, additional, Connolly, John E., additional, Lane, E. Birgitte, additional, Chew, Fook Tim, additional, Common, John E. A., additional, and Nagarajan, Niranjan, additional

Published
2016
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42. INC-Seq: accurate single molecule reads using nanopore sequencing.

Author

Chenhao Li, Chng, Kern Rei, Boey, Esther Jia Hui, Ng, Amanda Hui Qi, Wilm, Andreas, and Nagarajan, Niranjan

Subjects
*SINGLE molecules, *NANOPORES, *NANOSTRUCTURED materials
Abstract

Background: Nanopore sequencing provides a rapid, cheap and portable real-time sequencing platform with the potential to revolutionize genomics. However, several applications are limited by relatively high single-read error rates (>10 %), including RNA-seq, haplotype sequencing and 16S sequencing. Results: We developed the Intramolecular-ligated Nanopore Consensus Sequencing (INC-Seq) as a strategy for obtaining long and accurate nanopore reads, starting with low input DNA. Applying INC-Seq for 16S rRNA-based bacterial profiling generated full-length amplicon sequences with a median accuracy >97 %. Conclusions: INC-Seq reads enabled accurate species-level classification, identification of species at 0.1 % abundance and robust quantification of relative abundances, providing a cheap and effective approach for pathogen detection and microbiome profiling on the MinION system. [ABSTRACT FROM AUTHOR]

Published
2016
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45. Genomic Characterization of Dehalococcoides mccartyi Strain JNA That Reductively Dechlorinates Tetrachloroethene and Polychlorinated Biphenyls.

Author

Wang S, Chng KR, Chen C, Bedard DL, and He J

Subjects
Biodegradation, Environmental, Biological Assay, Chloroflexi metabolism, Genes, Bacterial, Genomics, Transcription, Genetic, Chloroflexi genetics, Genome, Bacterial, Halogenation, Polychlorinated Biphenyls metabolism, Tetrachloroethylene metabolism
Abstract

Dehalococcoides mccartyi strain JNA detoxifies highly chlorinated polychlorinated biphenyl (PCB) mixtures via 85 distinct dechlorination reactions, suggesting that it has great potential for PCB bioremediation. However, its genomic and functional gene information remain unknown due to extremely slow growth of strain JNA with PCBs. In this study, we used tetracholorethene (PCE) as an alternative electron acceptor to grow sufficient biomass of strain JNA for subsequent genome sequencing and functional gene identification. Analysis of the assembled draft genome (1 462 509 bp) revealed the presence of 29 putative reductive dehalogenase (RDase) genes. Among them, JNA_RD8 and JNA_RD11 genes were highly transcribed in both PCE- and PCB-fed cultures. Furthermore, in vitro assays with crude cell lysate from PCE grown cells revealed dechlorination activity against both PCE and 2,2',3,4,4',5,5'-heptachlorobiphenyl. These data suggest that both JNA_RD8 and JNA_RD11 may be bifunctional PCE/PCB RDases. This study deepens the knowledge of organohalide respiration of PCBs and facilitates in situ PCB-bioremediation with strain JNA.

Published
2015
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