37 results on '"Bork P"'
Search Results
2. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications
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Sterenborg, Rosalie B. T. M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A. L. M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C. M., Linneberg, Allan, Lominchar, Jesus V. T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N. A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I. A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H. R., Wouters, Hanneke J. C. M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W. A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, and Medici, Marco
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- 2024
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3. A catalog of small proteins from the global microbiome
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Yiqian Duan, Célio Dias Santos-Júnior, Thomas Sebastian Schmidt, Anthony Fullam, Breno L. S. de Almeida, Chengkai Zhu, Michael Kuhn, Xing-Ming Zhao, Peer Bork, and Luis Pedro Coelho
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Science - Abstract
Abstract Small open reading frames (smORFs) shorter than 100 codons are widespread and perform essential roles in microorganisms, where they encode proteins active in several cell functions, including signal pathways, stress response, and antibacterial activities. However, the ecology, distribution and role of small proteins in the global microbiome remain unknown. Here, we construct a global microbial smORFs catalog (GMSC) derived from 63,410 publicly available metagenomes across 75 distinct habitats and 87,920 high-quality isolate genomes. GMSC contains 965 million non-redundant smORFs with comprehensive annotations. We find that archaea harbor more smORFs proportionally than bacteria. We moreover provide a tool called GMSC-mapper to identify and annotate small proteins from microbial (meta)genomes. Overall, this publicly-available resource demonstrates the immense and underexplored diversity of small proteins.
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- 2024
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4. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications
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Rosalie B. T. M. Sterenborg, Inga Steinbrenner, Yong Li, Melissa N. Bujnis, Tatsuhiko Naito, Eirini Marouli, Tessel E. Galesloot, Oladapo Babajide, Laura Andreasen, Arne Astrup, Bjørn Olav Åsvold, Stefania Bandinelli, Marian Beekman, John P. Beilby, Jette Bork-Jensen, Thibaud Boutin, Jennifer A. Brody, Suzanne J. Brown, Ben Brumpton, Purdey J. Campbell, Anne R. Cappola, Graziano Ceresini, Layal Chaker, Daniel I. Chasman, Maria Pina Concas, Rodrigo Coutinho de Almeida, Simone M. Cross, Francesco Cucca, Ian J. Deary, Alisa Devedzic Kjaergaard, Justin B. Echouffo Tcheugui, Christina Ellervik, Johan G. Eriksson, Luigi Ferrucci, Jan Freudenberg, GHS DiscovEHR, Regeneron Genetics Center, Christian Fuchsberger, Christian Gieger, Franco Giulianini, Martin Gögele, Sarah E. Graham, Niels Grarup, Ivana Gunjača, Torben Hansen, Barbara N. Harding, Sarah E. Harris, Stig Haunsø, Caroline Hayward, Jennie Hui, Till Ittermann, J. Wouter Jukema, Eero Kajantie, Jørgen K. Kanters, Line L. Kårhus, Lambertus A. L. M. Kiemeney, Margreet Kloppenburg, Brigitte Kühnel, Jari Lahti, Claudia Langenberg, Bruno Lapauw, Graham Leese, Shuo Li, David C. M. Liewald, Allan Linneberg, Jesus V. T. Lominchar, Jian’an Luan, Nicholas G. Martin, Antonela Matana, Marcel E. Meima, Thomas Meitinger, Ingrid Meulenbelt, Braxton D. Mitchell, Line T. Møllehave, Samia Mora, Silvia Naitza, Matthias Nauck, Romana T. Netea-Maier, Raymond Noordam, Casia Nursyifa, Yukinori Okada, Stefano Onano, Areti Papadopoulou, Colin N. A. Palmer, Cristian Pattaro, Oluf Pedersen, Annette Peters, Maik Pietzner, Ozren Polašek, Peter P. Pramstaller, Bruce M. Psaty, Ante Punda, Debashree Ray, Paul Redmond, J. Brent Richards, Paul M. Ridker, Tom C. Russ, Kathleen A. Ryan, Morten Salling Olesen, Ulla T. Schultheiss, Elizabeth Selvin, Moneeza K. Siddiqui, Carlo Sidore, P. Eline Slagboom, Thorkild I. A. Sørensen, Enrique Soto-Pedre, Tim D. Spector, Beatrice Spedicati, Sundararajan Srinivasan, John M. Starr, David J. Stott, Toshiko Tanaka, Vesela Torlak, Stella Trompet, Johanna Tuhkanen, André G. Uitterlinden, Erik B. van den Akker, Tibbert van den Eynde, Melanie M. van der Klauw, Diana van Heemst, Charlotte Verroken, W. Edward Visser, Dina Vojinovic, Henry Völzke, Melanie Waldenberger, John P. Walsh, Nicholas J. Wareham, Stefan Weiss, Cristen J. Willer, Scott G. Wilson, Bruce H. R. Wolffenbuttel, Hanneke J. C. M. Wouters, Margaret J. Wright, Qiong Yang, Tatijana Zemunik, Wei Zhou, Gu Zhu, Sebastian Zöllner, Johannes W. A. Smit, Robin P. Peeters, Anna Köttgen, Alexander Teumer, and Marco Medici
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Science - Abstract
Abstract To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.
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- 2024
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5. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
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Budu-Aggrey, Ashley, Kilanowski, Anna, Sobczyk, Maria K., Shringarpure, Suyash S., Mitchell, Ruth, Reis, Kadri, Reigo, Anu, Mägi, Reedik, Nelis, Mari, Tanaka, Nao, Brumpton, Ben M., Thomas, Laurent F., Sole-Navais, Pol, Flatley, Christopher, Espuela-Ortiz, Antonio, Herrera-Luis, Esther, Lominchar, Jesus V. T., Bork-Jensen, Jette, Marenholz, Ingo, Arnau-Soler, Aleix, Jeong, Ayoung, Fawcett, Katherine A., Baurecht, Hansjorg, Rodriguez, Elke, Alves, Alexessander Couto, Kumar, Ashish, Sleiman, Patrick M., Chang, Xiao, Medina-Gomez, Carolina, Hu, Chen, Xu, Cheng-jian, Qi, Cancan, El-Heis, Sarah, Titcombe, Philip, Antoun, Elie, Fadista, João, Wang, Carol A., Thiering, Elisabeth, Wu, Baojun, Kress, Sara, Kothalawala, Dilini M., Kadalayil, Latha, Duan, Jiasong, Zhang, Hongmei, Hadebe, Sabelo, Hoffmann, Thomas, Jorgenson, Eric, Choquet, Hélène, Risch, Neil, Njølstad, Pål, Andreassen, Ole A., Johansson, Stefan, Almqvist, Catarina, Gong, Tong, Ullemar, Vilhelmina, Karlsson, Robert, Magnusson, Patrik K. E., Szwajda, Agnieszka, Burchard, Esteban G., Thyssen, Jacob P., Hansen, Torben, Kårhus, Line L., Dantoft, Thomas M., Jeanrenaud, Alexander C.S.N., Ghauri, Ahla, Arnold, Andreas, Homuth, Georg, Lau, Susanne, Nöthen, Markus M., Hübner, Norbert, Imboden, Medea, Visconti, Alessia, Falchi, Mario, Bataille, Veronique, Hysi, Pirro, Ballardini, Natalia, Boomsma, Dorret I., Hottenga, Jouke J., Müller-Nurasyid, Martina, Ahluwalia, Tarunveer S., Stokholm, Jakob, Chawes, Bo, Schoos, Ann-Marie M., Esplugues, Ana, Bustamante, Mariona, Raby, Benjamin, Arshad, Syed, German, Chris, Esko, Tõnu, Milani, Lili A., Metspalu, Andres, Terao, Chikashi, Abuabara, Katrina, Løset, Mari, Hveem, Kristian, Jacobsson, Bo, Pino-Yanes, Maria, Strachan, David P., Grarup, Niels, Linneberg, Allan, Lee, Young-Ae, Probst-Hensch, Nicole, Weidinger, Stephan, Jarvelin, Marjo-Riitta, Melén, Erik, Hakonarson, Hakon, Irvine, Alan D., Jarvis, Deborah, Nijsten, Tamar, Duijts, Liesbeth, Vonk, Judith M., Koppelmann, Gerard H., Godfrey, Keith M., Barton, Sheila J., Feenstra, Bjarke, Pennell, Craig E., Sly, Peter D., Holt, Patrick G., Williams, L. Keoki, Bisgaard, Hans, Bønnelykke, Klaus, Curtin, John, Simpson, Angela, Murray, Clare, Schikowski, Tamara, Bunyavanich, Supinda, Weiss, Scott T., Holloway, John W., Min, Josine L., Brown, Sara J., Standl, Marie, and Paternoster, Lavinia
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- 2023
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6. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
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Andrikopoulos, Petros, Aron-Wisnewsky, Judith, Chakaroun, Rima, Myridakis, Antonis, Forslund, Sofia K., Nielsen, Trine, Adriouch, Solia, Holmes, Bridget, Chilloux, Julien, Vieira-Silva, Sara, Falony, Gwen, Salem, Joe-Elie, Andreelli, Fabrizio, Belda, Eugeni, Kieswich, Julius, Chechi, Kanta, Puig-Castellvi, Francesc, Chevalier, Mickael, Le Chatelier, Emmanuelle, Olanipekun, Michael T., Hoyles, Lesley, Alves, Renato, Helft, Gerard, Isnard, Richard, Køber, Lars, Coelho, Luis Pedro, Rouault, Christine, Gauguier, Dominique, Gøtze, Jens Peter, Prifti, Edi, Froguel, Philippe, Zucker, Jean-Daniel, Bäckhed, Fredrik, Vestergaard, Henrik, Hansen, Torben, Oppert, Jean-Michel, Blüher, Matthias, Nielsen, Jens, Raes, Jeroen, Bork, Peer, Yaqoob, Muhammad M., Stumvoll, Michael, Pedersen, Oluf, Ehrlich, S. Dusko, Clément, Karine, and Dumas, Marc-Emmanuel
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- 2023
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7. Skeletal muscle derived Musclin protects the heart during pathological overload
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Szaroszyk, Malgorzata, Kattih, Badder, Martin-Garrido, Abel, Trogisch, Felix A., Dittrich, Gesine M., Grund, Andrea, Abouissa, Aya, Derlin, Katja, Meier, Martin, Holler, Tim, Korf-Klingebiel, Mortimer, Völker, Katharina, Garfias Macedo, Tania, Pablo Tortola, Cristina, Boschmann, Michael, Huang, Nora, Froese, Natali, Zwadlo, Carolin, Malek Mohammadi, Mona, Luo, Xiaojing, Wagner, Michael, Cordero, Julio, Geffers, Robert, Batkai, Sandor, Thum, Thomas, Bork, Nadja, Nikolaev, Viacheslav O., Müller, Oliver J., Katus, Hugo A., El-Armouche, Ali, Kraft, Theresia, Springer, Jochen, Dobreva, Gergana, Wollert, Kai C., Fielitz, Jens, von Haehling, Stephan, Kuhn, Michaela, Bauersachs, Johann, and Heineke, Joerg
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- 2022
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8. Cyanobacterial symbionts diverged in the late Cretaceous towards lineage-specific nitrogen fixation factories in single-celled phytoplankton.
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Cornejo-Castillo, Francisco M, Cabello, Ana M, Salazar, Guillem, Sánchez-Baracaldo, Patricia, Lima-Mendez, Gipsi, Hingamp, Pascal, Alberti, Adriana, Sunagawa, Shinichi, Bork, Peer, de Vargas, Colomban, Raes, Jeroen, Bowler, Chris, Wincker, Patrick, Zehr, Jonathan P, Gasol, Josep M, Massana, Ramon, and Acinas, Silvia G
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Phytoplankton ,Cyanobacteria ,Genomics ,Seawater ,Nitrogen Fixation ,Symbiosis ,Atlantic Ocean ,Biological Evolution ,Haptophyta ,Genetics ,Human Genome - Abstract
The unicellular cyanobacterium UCYN-A, one of the major contributors to nitrogen fixation in the open ocean, lives in symbiosis with single-celled phytoplankton. UCYN-A includes several closely related lineages whose partner fidelity, genome-wide expression and time of evolutionary divergence remain to be resolved. Here we detect and distinguish UCYN-A1 and UCYN-A2 lineages in symbiosis with two distinct prymnesiophyte partners in the South Atlantic Ocean. Both symbiotic systems are lineage specific and differ in the number of UCYN-A cells involved. Our analyses infer a streamlined genome expression towards nitrogen fixation in both UCYN-A lineages. Comparative genomics reveal a strong purifying selection in UCYN-A1 and UCYN-A2 with a diversification process ∼91 Myr ago, in the late Cretaceous, after the low-nutrient regime period occurred during the Jurassic. These findings suggest that UCYN-A diversified in a co-evolutionary process, wherein their prymnesiophyte partners acted as a barrier driving an allopatric speciation of extant UCYN-A lineages.
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- 2016
9. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.
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Wessel, Jennifer, Chu, Audrey Y, Willems, Sara M, Wang, Shuai, Yaghootkar, Hanieh, Brody, Jennifer A, Dauriz, Marco, Hivert, Marie-France, Raghavan, Sridharan, Lipovich, Leonard, Hidalgo, Bertha, Fox, Keolu, Huffman, Jennifer E, An, Ping, Lu, Yingchang, Rasmussen-Torvik, Laura J, Grarup, Niels, Ehm, Margaret G, Li, Li, Baldridge, Abigail S, Stančáková, Alena, Abrol, Ravinder, Besse, Céline, Boland, Anne, Bork-Jensen, Jette, Fornage, Myriam, Freitag, Daniel F, Garcia, Melissa E, Guo, Xiuqing, Hara, Kazuo, Isaacs, Aaron, Jakobsdottir, Johanna, Lange, Leslie A, Layton, Jill C, Li, Man, Hua Zhao, Jing, Meidtner, Karina, Morrison, Alanna C, Nalls, Mike A, Peters, Marjolein J, Sabater-Lleal, Maria, Schurmann, Claudia, Silveira, Angela, Smith, Albert V, Southam, Lorraine, Stoiber, Marcus H, Strawbridge, Rona J, Taylor, Kent D, Varga, Tibor V, Allin, Kristine H, Amin, Najaf, Aponte, Jennifer L, Aung, Tin, Barbieri, Caterina, Bihlmeyer, Nathan A, Boehnke, Michael, Bombieri, Cristina, Bowden, Donald W, Burns, Sean M, Chen, Yuning, Chen, Yii-DerI, Cheng, Ching-Yu, Correa, Adolfo, Czajkowski, Jacek, Dehghan, Abbas, Ehret, Georg B, Eiriksdottir, Gudny, Escher, Stefan A, Farmaki, Aliki-Eleni, Frånberg, Mattias, Gambaro, Giovanni, Giulianini, Franco, Goddard, William A, Goel, Anuj, Gottesman, Omri, Grove, Megan L, Gustafsson, Stefan, Hai, Yang, Hallmans, Göran, Heo, Jiyoung, Hoffmann, Per, Ikram, Mohammad K, Jensen, Richard A, Jørgensen, Marit E, Jørgensen, Torben, Karaleftheri, Maria, Khor, Chiea C, Kirkpatrick, Andrea, Kraja, Aldi T, Kuusisto, Johanna, Lange, Ethan M, Lee, IT, Lee, Wen-Jane, Leong, Aaron, Liao, Jiemin, Liu, Chunyu, Liu, Yongmei, Lindgren, Cecilia M, Linneberg, Allan, and Malerba, Giovanni
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EPIC-InterAct Consortium ,Humans ,Diabetes Mellitus ,Type 2 ,Genetic Predisposition to Disease ,Insulin ,Glucose-6-Phosphatase ,Blood Glucose ,Oligonucleotide Array Sequence Analysis ,Fasting ,Polymorphism ,Single Nucleotide ,African Continental Ancestry Group ,European Continental Ancestry Group ,Genetic Variation ,Genetic Loci ,Genetic Association Studies ,Mutation Rate ,Exome ,Glucagon-Like Peptide-1 Receptor ,Diabetes Mellitus ,Type 2 ,Polymorphism ,Single Nucleotide ,Diabetes ,Genetics ,Nutrition ,Clinical Research ,Prevention ,Human Genome ,2.1 Biological and endogenous factors ,Metabolic and Endocrine - Abstract
Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01 mmol l(-1), P=3.4 × 10(-12)), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035 pmolinsulin mmolglucose(-1), P=0.048), but higher 2-h glucose (β=0.16±0.05 mmol l(-1), P=4.3 × 10(-4)). We identify a gene-based association with FG at G6PC2 (pSKAT=6.8 × 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004 mmol l(-1), P=1.3 × 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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- 2015
10. FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses
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Ahluwalia, Tarunveer S., Eliasen, Anders U., Sevelsted, Astrid, Pedersen, Casper-Emil T., Stokholm, Jakob, Chawes, Bo, Bork-Jensen, Jette, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Sharma, Amitabh, Weiss, Scott T., Evans, Michael D., Jackson, Daniel J., Morin, Andreanne, Krogfelt, Karen A., Schjørring, Susanne, Mortensen, Preben B., Hougaard, David M., Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Mors, Ole, Nordentoft, Merete, Børglum, Anders D., Werge, Thomas, Agerbo, Esben, Gern, James E., Lemanske, Jr., Robert F., Ober, Carole, Pedersen, Anders G., Bisgaard, Hans, and Bønnelykke, Klaus
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- 2020
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11. Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism
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Williams, Kristine, Ingerslev, Lars R., Bork-Jensen, Jette, Wohlwend, Martin, Hansen, Ann Normann, Small, Lewin, Ribel-Madsen, Rasmus, Astrup, Arne, Pedersen, Oluf, Auwerx, Johan, Workman, Christopher T., Grarup, Niels, Hansen, Torben, and Barrès, Romain
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- 2020
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12. Microbial abundance, activity and population genomic profiling with mOTUs2
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Milanese, Alessio, Mende, Daniel R, Paoli, Lucas, Salazar, Guillem, Ruscheweyh, Hans-Joachim, Cuenca, Miguelangel, Hingamp, Pascal, Alves, Renato, Costea, Paul I, Coelho, Luis Pedro, Schmidt, Thomas S. B., Almeida, Alexandre, Mitchell, Alex L, Finn, Robert D., Huerta-Cepas, Jaime, Bork, Peer, Zeller, Georg, and Sunagawa, Shinichi
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- 2019
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13. Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
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Hennrich, Marco L., Romanov, Natalie, Horn, Patrick, Jaeger, Samira, Eckstein, Volker, Steeples, Violetta, Ye, Fei, Ding, Ximing, Poisa-Beiro, Laura, Lai, Mang Ching, Lang, Benjamin, Boultwood, Jacqueline, Luft, Thomas, Zaugg, Judith B., Pellagatti, Andrea, Bork, Peer, Aloy, Patrick, Gavin, Anne-Claude, and Ho, Anthony D.
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- 2018
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14. CXCL12 and MYC control energy metabolism to support adaptive responses after kidney injury
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Yakulov, Toma A., Todkar, Abhijeet P., Slanchev, Krasimir, Wiegel, Johannes, Bona, Alexandra, Groß, Martin, Scholz, Alexander, Hess, Isabell, Wurditsch, Anne, Grahammer, Florian, Huber, Tobias B., Lecaudey, Virginie, Bork, Tillmann, Hochrein, Jochen, Boerries, Melanie, Leenders, Justine, de Tullio, Pascal, Jouret, François, Kramer-Zucker, Albrecht, and Walz, Gerd
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- 2018
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15. Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios
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Besenbacher, Søren, Liu, Siyang, Izarzugaza, José M. G., Grove, Jakob, Belling, Kirstine, Bork-Jensen, Jette, Huang, Shujia, Als, Thomas D., Li, Shengting, Yadav, Rachita, Rubio-García, Arcadio, Lescai, Francesco, Demontis, Ditte, Rao, Junhua, Ye, Weijian, Mailund, Thomas, Friborg, Rune M., Pedersen, Christian N. S., Xu, Ruiqi, Sun, Jihua, Liu, Hao, Wang, Ou, Cheng, Xiaofang, Flores, David, Rydza, Emil, Rapacki, Kristoffer, Damm Sørensen, John, Chmura, Piotr, Westergaard, David, Dworzynski, Piotr, Sørensen, Thorkild I. A., Lund, Ole, Hansen, Torben, Xu, Xun, Li, Ning, Bolund, Lars, Pedersen, Oluf, Eiberg, Hans, Krogh, Anders, Børglum, Anders D., Brunak, Søren, Kristiansen, Karsten, Schierup, Mikkel H., Wang, Jun, Gupta, Ramneek, Villesen, Palle, and Rasmussen, Simon
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- 2015
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16. European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation
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Ashley Budu-Aggrey, Anna Kilanowski, Maria K. Sobczyk, andMe Research Team, Suyash S. Shringarpure, Ruth Mitchell, Kadri Reis, Anu Reigo, Estonian Biobank Research Team, Reedik Mägi, Mari Nelis, Nao Tanaka, Ben M. Brumpton, Laurent F. Thomas, Pol Sole-Navais, Christopher Flatley, Antonio Espuela-Ortiz, Esther Herrera-Luis, Jesus V. T. Lominchar, Jette Bork-Jensen, Ingo Marenholz, Aleix Arnau-Soler, Ayoung Jeong, Katherine A. Fawcett, Hansjorg Baurecht, Elke Rodriguez, Alexessander Couto Alves, Ashish Kumar, Patrick M. Sleiman, Xiao Chang, Carolina Medina-Gomez, Chen Hu, Cheng-jian Xu, Cancan Qi, Sarah El-Heis, Philip Titcombe, Elie Antoun, João Fadista, Carol A. Wang, Elisabeth Thiering, Baojun Wu, Sara Kress, Dilini M. Kothalawala, Latha Kadalayil, Jiasong Duan, Hongmei Zhang, Sabelo Hadebe, Thomas Hoffmann, Eric Jorgenson, Hélène Choquet, Neil Risch, Pål Njølstad, Ole A. Andreassen, Stefan Johansson, Catarina Almqvist, Tong Gong, Vilhelmina Ullemar, Robert Karlsson, Patrik K. E. Magnusson, Agnieszka Szwajda, Esteban G. Burchard, Jacob P. Thyssen, Torben Hansen, Line L. Kårhus, Thomas M. Dantoft, Alexander C.S.N. Jeanrenaud, Ahla Ghauri, Andreas Arnold, Georg Homuth, Susanne Lau, Markus M. Nöthen, Norbert Hübner, Medea Imboden, Alessia Visconti, Mario Falchi, Veronique Bataille, Pirro Hysi, Natalia Ballardini, Dorret I. Boomsma, Jouke J. Hottenga, Martina Müller-Nurasyid, Tarunveer S. Ahluwalia, Jakob Stokholm, Bo Chawes, Ann-Marie M. Schoos, Ana Esplugues, Mariona Bustamante, Benjamin Raby, Syed Arshad, Chris German, Tõnu Esko, Lili A. Milani, Andres Metspalu, Chikashi Terao, Katrina Abuabara, Mari Løset, Kristian Hveem, Bo Jacobsson, Maria Pino-Yanes, David P. Strachan, Niels Grarup, Allan Linneberg, Young-Ae Lee, Nicole Probst-Hensch, Stephan Weidinger, Marjo-Riitta Jarvelin, Erik Melén, Hakon Hakonarson, Alan D. Irvine, Deborah Jarvis, Tamar Nijsten, Liesbeth Duijts, Judith M. Vonk, Gerard H. Koppelmann, Keith M. Godfrey, Sheila J. Barton, Bjarke Feenstra, Craig E. Pennell, Peter D. Sly, Patrick G. Holt, L. Keoki Williams, Hans Bisgaard, Klaus Bønnelykke, John Curtin, Angela Simpson, Clare Murray, Tamara Schikowski, Supinda Bunyavanich, Scott T. Weiss, John W. Holloway, Josine L. Min, Sara J. Brown, Marie Standl, and Lavinia Paternoster
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Science - Abstract
Abstract Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.
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- 2023
- Full Text
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17. Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
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Petros Andrikopoulos, Judith Aron-Wisnewsky, Rima Chakaroun, Antonis Myridakis, Sofia K. Forslund, Trine Nielsen, Solia Adriouch, Bridget Holmes, Julien Chilloux, Sara Vieira-Silva, Gwen Falony, Joe-Elie Salem, Fabrizio Andreelli, Eugeni Belda, Julius Kieswich, Kanta Chechi, Francesc Puig-Castellvi, Mickael Chevalier, Emmanuelle Le Chatelier, Michael T. Olanipekun, Lesley Hoyles, Renato Alves, Gerard Helft, Richard Isnard, Lars Køber, Luis Pedro Coelho, Christine Rouault, Dominique Gauguier, Jens Peter Gøtze, Edi Prifti, Philippe Froguel, The MetaCardis Consortium, Jean-Daniel Zucker, Fredrik Bäckhed, Henrik Vestergaard, Torben Hansen, Jean-Michel Oppert, Matthias Blüher, Jens Nielsen, Jeroen Raes, Peer Bork, Muhammad M. Yaqoob, Michael Stumvoll, Oluf Pedersen, S. Dusko Ehrlich, Karine Clément, and Marc-Emmanuel Dumas
- Subjects
Science - Abstract
Abstract The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied “explainable” machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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- 2023
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18. Skeletal muscle derived Musclin protects the heart during pathological overload
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Malgorzata Szaroszyk, Badder Kattih, Abel Martin-Garrido, Felix A. Trogisch, Gesine M. Dittrich, Andrea Grund, Aya Abouissa, Katja Derlin, Martin Meier, Tim Holler, Mortimer Korf-Klingebiel, Katharina Völker, Tania Garfias Macedo, Cristina Pablo Tortola, Michael Boschmann, Nora Huang, Natali Froese, Carolin Zwadlo, Mona Malek Mohammadi, Xiaojing Luo, Michael Wagner, Julio Cordero, Robert Geffers, Sandor Batkai, Thomas Thum, Nadja Bork, Viacheslav O. Nikolaev, Oliver J. Müller, Hugo A. Katus, Ali El-Armouche, Theresia Kraft, Jochen Springer, Gergana Dobreva, Kai C. Wollert, Jens Fielitz, Stephan von Haehling, Michaela Kuhn, Johann Bauersachs, and Joerg Heineke
- Subjects
Science - Abstract
Cachexia is associated with poor prognosis in heart failure. Here the authors show that mice and patients with cardiac cachexia display reduced skeletal muscle expression and circulating levels of Musclin. Musclin ablation in skeletal muscle worsens, while its muscle-specific overexpression ameliorates heart failure in mice.
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- 2022
- Full Text
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19. FUT2–ABO epistasis increases the risk of early childhood asthma and Streptococcus pneumoniae respiratory illnesses
- Author
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Tarunveer S. Ahluwalia, Anders U. Eliasen, Astrid Sevelsted, Casper-Emil T. Pedersen, Jakob Stokholm, Bo Chawes, Jette Bork-Jensen, Niels Grarup, Oluf Pedersen, Torben Hansen, Allan Linneberg, Amitabh Sharma, Scott T. Weiss, Michael D. Evans, Daniel J. Jackson, Andreanne Morin, Karen A. Krogfelt, Susanne Schjørring, Preben B. Mortensen, David M. Hougaard, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Ole Mors, Merete Nordentoft, Anders D. Børglum, Thomas Werge, Esben Agerbo, James E. Gern, Robert F. Lemanske, Carole Ober, Anders G. Pedersen, Hans Bisgaard, and Klaus Bønnelykke
- Subjects
Science - Abstract
Genetic variants discovered through genome-wide association studies for asthma together account for a small portion of the heritability. Here, the authors identify a possible epistatic relationship between coding variants in FUT2 and ABO, especially pronounced in severe and early onset asthma.
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- 2020
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20. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- Author
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Antonio Molinaro, Pierre Bel Lassen, Marcus Henricsson, Hao Wu, Solia Adriouch, Eugeni Belda, Rima Chakaroun, Trine Nielsen, Per-Olof Bergh, Christine Rouault, Sébastien André, Florian Marquet, Fabrizio Andreelli, Joe-Elie Salem, Karen Assmann, Jean-Philippe Bastard, Sofia Forslund, Emmanuelle Le Chatelier, Gwen Falony, Nicolas Pons, Edi Prifti, Benoit Quinquis, Hugo Roume, Sara Vieira-Silva, Tue H. Hansen, Helle Krogh Pedersen, Christian Lewinter, Nadja B. Sønderskov, The MetaCardis Consortium, Lars Køber, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker, Pilar Galan, Marc-Emmanuel Dumas, Jeroen Raes, Jean-Michel Oppert, Ivica Letunic, Jens Nielsen, Peer Bork, S. Dusko Ehrlich, Michael Stumvoll, Oluf Pedersen, Judith Aron-Wisnewsky, Karine Clément, and Fredrik Bäckhed
- Subjects
Science - Abstract
Gut microbial metabolism of nutrients contributes to metabolic diseases, and the histidine metabolite imidazole propionate (ImP) is produced by type 2 diabetes (T2D) associated microbiome. Here the authors report that circulating ImP levels are increased in subjects with prediabetes or T2D in three European populations, and this increase associates with altered gut microbiota rather than dietary histidine.
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- 2020
- Full Text
- View/download PDF
21. Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism
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Kristine Williams, Lars R. Ingerslev, Jette Bork-Jensen, Martin Wohlwend, Ann Normann Hansen, Lewin Small, Rasmus Ribel-Madsen, Arne Astrup, Oluf Pedersen, Johan Auwerx, Christopher T. Workman, Niels Grarup, Torben Hansen, and Romain Barrès
- Subjects
Science - Abstract
Obesity and type 2 diabetes (T2D) are metabolic disorders characterized by insulin resistance in skeletal muscle. Here, the authors map skeletal muscle enhancer elements dynamically regulated after exposure to free fatty acid palmitate or inflammatory cytokine TNFα and identify target genes involved in metabolic dysfunction in skeletal muscle.
- Published
- 2020
- Full Text
- View/download PDF
22. Microbial abundance, activity and population genomic profiling with mOTUs2
- Author
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Alessio Milanese, Daniel R Mende, Lucas Paoli, Guillem Salazar, Hans-Joachim Ruscheweyh, Miguelangel Cuenca, Pascal Hingamp, Renato Alves, Paul I Costea, Luis Pedro Coelho, Thomas S. B. Schmidt, Alexandre Almeida, Alex L Mitchell, Robert D. Finn, Jaime Huerta-Cepas, Peer Bork, Georg Zeller, and Shinichi Sunagawa
- Subjects
Science - Abstract
Metagenomic analysis based on universal phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) is a useful strategy, especially for microbial species without reference genomes. Here, the authors develop mOTUs2, an updated and functionally extended profiling tool for microbial abundance, activity and population profiling.
- Published
- 2019
- Full Text
- View/download PDF
23. Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline
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Marco L. Hennrich, Natalie Romanov, Patrick Horn, Samira Jaeger, Volker Eckstein, Violetta Steeples, Fei Ye, Ximing Ding, Laura Poisa-Beiro, Mang Ching Lai, Benjamin Lang, Jacqueline Boultwood, Thomas Luft, Judith B. Zaugg, Andrea Pellagatti, Peer Bork, Patrick Aloy, Anne-Claude Gavin, and Anthony D. Ho
- Subjects
Science - Abstract
Ageing causes an inability to replace damaged tissue. Here, the authors perform proteomics analyses of human haematopoietic stem cells and other cells in the bone marrow niche at different ages and show changes in central carbon metabolism, reduced bone marrow niche function, and enhanced myeloid differentiation.
- Published
- 2018
- Full Text
- View/download PDF
24. CXCL12 and MYC control energy metabolism to support adaptive responses after kidney injury
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Toma A. Yakulov, Abhijeet P. Todkar, Krasimir Slanchev, Johannes Wiegel, Alexandra Bona, Martin Groß, Alexander Scholz, Isabell Hess, Anne Wurditsch, Florian Grahammer, Tobias B. Huber, Virginie Lecaudey, Tillmann Bork, Jochen Hochrein, Melanie Boerries, Justine Leenders, Pascal de Tullio, François Jouret, Albrecht Kramer-Zucker, and Gerd Walz
- Subjects
Science - Abstract
Injuries in the embryonal kidney can be repaired by a cell migratory response but how this is regulated at a molecular level is unclear. Here, the authors show in mice that deletion of Cxcl12 and Myc delays pronephros injury repair by changing mitochondrial metabolism and glycolysis.
- Published
- 2018
- Full Text
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25. Single-cell genomics of multiple uncultured stramenopiles reveals underestimated functional diversity across oceans
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Yoann Seeleuthner, Samuel Mondy, Vincent Lombard, Quentin Carradec, Eric Pelletier, Marc Wessner, Jade Leconte, Jean-François Mangot, Julie Poulain, Karine Labadie, Ramiro Logares, Shinichi Sunagawa, Véronique de Berardinis, Marcel Salanoubat, Céline Dimier, Stefanie Kandels-Lewis, Marc Picheral, Sarah Searson, Tara Oceans Coordinators, Stephane Pesant, Nicole Poulton, Ramunas Stepanauskas, Peer Bork, Chris Bowler, Pascal Hingamp, Matthew B. Sullivan, Daniele Iudicone, Ramon Massana, Jean-Marc Aury, Bernard Henrissat, Eric Karsenti, Olivier Jaillon, Mike Sieracki, Colomban de Vargas, and Patrick Wincker
- Subjects
Science - Abstract
The biology of many marine protists, such as stramenopiles, remains obscure. Here, the authors exploit single-cell genomics and metagenomics to analyze the genome content and apparent oceanic distribution of seven prevalent lineages of uncultured heterotrophic stramenopiles.
- Published
- 2018
- Full Text
- View/download PDF
26. A global ocean atlas of eukaryotic genes
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Quentin Carradec, Eric Pelletier, Corinne Da Silva, Adriana Alberti, Yoann Seeleuthner, Romain Blanc-Mathieu, Gipsi Lima-Mendez, Fabio Rocha, Leila Tirichine, Karine Labadie, Amos Kirilovsky, Alexis Bertrand, Stefan Engelen, Mohammed-Amin Madoui, Raphaël Méheust, Julie Poulain, Sarah Romac, Daniel J. Richter, Genki Yoshikawa, Céline Dimier, Stefanie Kandels-Lewis, Marc Picheral, Sarah Searson, Tara Oceans Coordinators, Olivier Jaillon, Jean-Marc Aury, Eric Karsenti, Matthew B. Sullivan, Shinichi Sunagawa, Peer Bork, Fabrice Not, Pascal Hingamp, Jeroen Raes, Lionel Guidi, Hiroyuki Ogata, Colomban de Vargas, Daniele Iudicone, Chris Bowler, and Patrick Wincker
- Subjects
Science - Abstract
Marine microbial eukaryotes and zooplankton display enormous diversity and largely unexplored physiologies. Here, the authors use metatranscriptomics to analyze four organismal size fractions from open-ocean stations, providing the largest reference collection of eukaryotic transcripts from any single biome.
- Published
- 2018
- Full Text
- View/download PDF
27. Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias
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Christiane Jungen, Katharina Scherschel, Christian Eickholt, Pawel Kuklik, Niklas Klatt, Nadja Bork, Tim Salzbrunn, Fares Alken, Stephan Angendohr, Christiane Klene, Janos Mester, Nikolaj Klöcker, Marieke W. Veldkamp, Udo Schumacher, Stephan Willems, Viacheslav O. Nikolaev, and Christian Meyer
- Subjects
Science - Abstract
Catheter ablation is a common therapy for atrial fibrillation but disrupts cardiac cholinergic neurons. Here the authors report that cholinergic neurons innervate heart ventricles and show that their ablation leads to increased susceptibility to ventricular arrhythmias in mouse models and in patients.
- Published
- 2017
- Full Text
- View/download PDF
28. Author Correction: Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- Author
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Antonio Molinaro, Pierre Bel Lassen, Marcus Henricsson, Hao Wu, Solia Adriouch, Eugeni Belda, Rima Chakaroun, Trine Nielsen, Per-Olof Bergh, Christine Rouault, Sébastien André, Florian Marquet, Fabrizio Andreelli, Joe-Elie Salem, Karen Assmann, Jean-Philippe Bastard, Sofia Forslund, Emmanuelle Le Chatelier, Gwen Falony, Nicolas Pons, Edi Prifti, Benoit Quinquis, Hugo Roume, Sara Vieira-Silva, Tue H. Hansen, Helle Krogh Pedersen, Christian Lewinter, Nadja B. Sønderskov, The MetaCardis Consortium, Lars Køber, Henrik Vestergaard, Torben Hansen, Jean-Daniel Zucker, Pilar Galan, Marc-Emmanuel Dumas, Jeroen Raes, Jean-Michel Oppert, Ivica Letunic, Jens Nielsen, Peer Bork, S. Dusko Ehrlich, Michael Stumvoll, Oluf Pedersen, Judith Aron-Wisnewsky, Karine Clément, and Fredrik Bäckhed
- Subjects
Science - Abstract
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20412-9.
- Published
- 2020
- Full Text
- View/download PDF
29. Energy efficiency trade-offs drive nucleotide usage in transcribed regions
- Author
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Wei-Hua Chen, Guanting Lu, Peer Bork, Songnian Hu, and Martin J. Lercher
- Subjects
Science - Abstract
Substantial cellular resources are devoted to nucleotide biosynthesis. Here the authors propose that transcribed regions prefer ‘cheaper’ nucleotides, which appears true for synonymous sites, although more expensive nucleotides coding for cheaper amino acids are selected for at non-synonymous sites.
- Published
- 2016
- Full Text
- View/download PDF
30. Cyanobacterial symbionts diverged in the late Cretaceous towards lineage-specific nitrogen fixation factories in single-celled phytoplankton
- Author
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Francisco M. Cornejo-Castillo, Ana M. Cabello, Guillem Salazar, Patricia Sánchez-Baracaldo, Gipsi Lima-Mendez, Pascal Hingamp, Adriana Alberti, Shinichi Sunagawa, Peer Bork, Colomban de Vargas, Jeroen Raes, Chris Bowler, Patrick Wincker, Jonathan P. Zehr, Josep M. Gasol, Ramon Massana, and Silvia G. Acinas
- Subjects
Science - Abstract
Nitrogen fixation in oceans is facilitated by associations between marine phytoplankton and cyanobacteria such as UCYN-A. Here, Cornejo-Castillo et al. show that UCYN-A diversified in the late Cretaceous under strong purifying selection to become lineage-specific symbiont partners with different prymnesiophytes.
- Published
- 2016
- Full Text
- View/download PDF
31. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children
- Author
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Katri Korpela, Anne Salonen, Lauri J. Virta, Riina A. Kekkonen, Kristoffer Forslund, Peer Bork, and Willem M. de Vos
- Subjects
Science - Abstract
The impact of antibiotics on the microbiome and health of children is poorly understood. Here, Korpela et al. study the gut microbiome of 142 children and show that the use of macrolides, but not penicillins, is associated with long-lasting shifts in microbiota composition and increased risk of asthma and overweight.
- Published
- 2016
- Full Text
- View/download PDF
32. Author Correction: Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.
- Author
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Molinaro A, Bel Lassen P, Henricsson M, Wu H, Adriouch S, Belda E, Chakaroun R, Nielsen T, Bergh PO, Rouault C, André S, Marquet F, Andreelli F, Salem JE, Assmann K, Bastard JP, Forslund S, Le Chatelier E, Falony G, Pons N, Prifti E, Quinquis B, Roume H, Vieira-Silva S, Hansen TH, Pedersen HK, Lewinter C, Sønderskov NB, Køber L, Vestergaard H, Hansen T, Zucker JD, Galan P, Dumas ME, Raes J, Oppert JM, Letunic I, Nielsen J, Bork P, Ehrlich SD, Stumvoll M, Pedersen O, Aron-Wisnewsky J, Clément K, and Bäckhed F
- Published
- 2020
- Full Text
- View/download PDF
33. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology.
- Author
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Molinaro A, Bel Lassen P, Henricsson M, Wu H, Adriouch S, Belda E, Chakaroun R, Nielsen T, Bergh PO, Rouault C, André S, Marquet F, Andreelli F, Salem JE, Assmann K, Bastard JP, Forslund S, Le Chatelier E, Falony G, Pons N, Prifti E, Quinquis B, Roume H, Vieira-Silva S, Hansen TH, Pedersen HK, Lewinter C, Sønderskov NB, Køber L, Vestergaard H, Hansen T, Zucker JD, Galan P, Dumas ME, Raes J, Oppert JM, Letunic I, Nielsen J, Bork P, Ehrlich SD, Stumvoll M, Pedersen O, Aron-Wisnewsky J, Clément K, and Bäckhed F
- Subjects
- Adult, Aged, Bacteria classification, Bacteria genetics, Bacteria isolation & purification, Bacteria metabolism, Cohort Studies, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 metabolism, Female, Histidine metabolism, Humans, Male, Middle Aged, Diabetes Mellitus, Type 2 microbiology, Gastrointestinal Microbiome, Imidazoles blood
- Abstract
Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
- Published
- 2020
- Full Text
- View/download PDF
34. A global ocean atlas of eukaryotic genes.
- Author
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Carradec Q, Pelletier E, Da Silva C, Alberti A, Seeleuthner Y, Blanc-Mathieu R, Lima-Mendez G, Rocha F, Tirichine L, Labadie K, Kirilovsky A, Bertrand A, Engelen S, Madoui MA, Méheust R, Poulain J, Romac S, Richter DJ, Yoshikawa G, Dimier C, Kandels-Lewis S, Picheral M, Searson S, Jaillon O, Aury JM, Karsenti E, Sullivan MB, Sunagawa S, Bork P, Not F, Hingamp P, Raes J, Guidi L, Ogata H, de Vargas C, Iudicone D, Bowler C, and Wincker P
- Subjects
- Amino Acid Sequence, Animals, Atlases as Topic, Bacteria classification, Bacteria genetics, Biodiversity, Ecosystem, Eukaryota classification, Eukaryotic Cells cytology, Metagenomics methods, Oceans and Seas, Phytoplankton classification, Phytoplankton genetics, Seawater, Viruses classification, Viruses genetics, Zooplankton classification, Aquatic Organisms, Eukaryota genetics, Eukaryotic Cells metabolism, Metagenome, Phylogeny, Zooplankton genetics
- Abstract
While our knowledge about the roles of microbes and viruses in the ocean has increased tremendously due to recent advances in genomics and metagenomics, research on marine microbial eukaryotes and zooplankton has benefited much less from these new technologies because of their larger genomes, their enormous diversity, and largely unexplored physiologies. Here, we use a metatranscriptomics approach to capture expressed genes in open ocean Tara Oceans stations across four organismal size fractions. The individual sequence reads cluster into 116 million unigenes representing the largest reference collection of eukaryotic transcripts from any single biome. The catalog is used to unveil functions expressed by eukaryotic marine plankton, and to assess their functional biogeography. Almost half of the sequences have no similarity with known proteins, and a great number belong to new gene families with a restricted distribution in the ocean. Overall, the resource provides the foundations for exploring the roles of marine eukaryotes in ocean ecology and biogeochemistry.
- Published
- 2018
- Full Text
- View/download PDF
35. Single-cell genomics of multiple uncultured stramenopiles reveals underestimated functional diversity across oceans.
- Author
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Seeleuthner Y, Mondy S, Lombard V, Carradec Q, Pelletier E, Wessner M, Leconte J, Mangot JF, Poulain J, Labadie K, Logares R, Sunagawa S, de Berardinis V, Salanoubat M, Dimier C, Kandels-Lewis S, Picheral M, Searson S, Pesant S, Poulton N, Stepanauskas R, Bork P, Bowler C, Hingamp P, Sullivan MB, Iudicone D, Massana R, Aury JM, Henrissat B, Karsenti E, Jaillon O, Sieracki M, de Vargas C, and Wincker P
- Abstract
Single-celled eukaryotes (protists) are critical players in global biogeochemical cycling of nutrients and energy in the oceans. While their roles as primary producers and grazers are well appreciated, other aspects of their life histories remain obscure due to challenges in culturing and sequencing their natural diversity. Here, we exploit single-cell genomics and metagenomics data from the circumglobal Tara Oceans expedition to analyze the genome content and apparent oceanic distribution of seven prevalent lineages of uncultured heterotrophic stramenopiles. Based on the available data, each sequenced genome or genotype appears to have a specific oceanic distribution, principally correlated with water temperature and depth. The genome content provides hypotheses for specialization in terms of cell motility, food spectra, and trophic stages, including the potential impact on their lifestyles of horizontal gene transfer from prokaryotes. Our results support the idea that prominent heterotrophic marine protists perform diverse functions in ocean ecology.
- Published
- 2018
- Full Text
- View/download PDF
36. Energy efficiency trade-offs drive nucleotide usage in transcribed regions.
- Author
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Chen WH, Lu G, Bork P, Hu S, and Lercher MJ
- Subjects
- Base Composition, Base Pairing, Biological Evolution, Codon, Models, Genetic, Mutation, Operon, Selection, Genetic, Thermodynamics, Amino Acids genetics, Bacteria genetics, Genome, Bacterial, Nucleotides genetics, Protein Biosynthesis, Transcription, Genetic
- Abstract
Efficient nutrient usage is a trait under universal selection. A substantial part of cellular resources is spent on making nucleotides. We thus expect preferential use of cheaper nucleotides especially in transcribed sequences, which are often amplified thousand-fold compared with genomic sequences. To test this hypothesis, we derive a mutation-selection-drift equilibrium model for nucleotide skews (strand-specific usage of 'A' versus 'T' and 'G' versus 'C'), which explains nucleotide skews across 1,550 prokaryotic genomes as a consequence of selection on efficient resource usage. Transcription-related selection generally favours the cheaper nucleotides 'U' and 'C' at synonymous sites. However, the information encoded in mRNA is further amplified through translation. Due to unexpected trade-offs in the codon table, cheaper nucleotides encode on average energetically more expensive amino acids. These trade-offs apply to both strand-specific nucleotide usage and GC content, causing a universal bias towards the more expensive nucleotides 'A' and 'G' at non-synonymous coding sites.
- Published
- 2016
- Full Text
- View/download PDF
37. Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children.
- Author
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Korpela K, Salonen A, Virta LJ, Kekkonen RA, Forslund K, Bork P, and de Vos WM
- Subjects
- Anti-Bacterial Agents adverse effects, Bacteria classification, Bacteria genetics, Child, Child, Preschool statistics & numerical data, Cohort Studies, Day Care, Medical statistics & numerical data, Feces microbiology, Female, Finland, Humans, Macrolides adverse effects, Male, Anti-Bacterial Agents therapeutic use, Bacteria isolation & purification, Bacterial Infections drug therapy, Gastrointestinal Microbiome drug effects, Macrolides therapeutic use
- Abstract
Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2-7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.
- Published
- 2016
- Full Text
- View/download PDF
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