Search

Your search keyword '"Birney, Ewan"' showing total 1,073 results
Start Over Author "Birney, Ewan"
1,073 results on '"Birney, Ewan"'

3. Longitudinal metabolite and protein trajectories prior to diabetes mellitus diagnosis in Danish blood donors: a nested case–control study

Author

Lundgaard, Agnete T., Westergaard, David, Röder, Timo, Burgdorf, Kristoffer S., Larsen, Margit H., Schwinn, Michael, Thørner, Lise W., Sørensen, Erik, Nielsen, Kaspar R., Hjalgrim, Henrik, Erikstrup, Christian, Kjerulff, Bertram D., Hindhede, Lotte, Hansen, Thomas F., Nyegaard, Mette, Birney, Ewan, Stefansson, Hreinn, Stefánsson, Kári, Pedersen, Ole B. V., Ostrowski, Sisse R., Rossing, Peter, Ullum, Henrik, Mortensen, Laust H., Vistisen, Dorte, Banasik, Karina, and Brunak, Søren

Published
2024
Full Text
View/download PDF

7. The language of race, ethnicity, and ancestry in human genetic research

Author

Birney, Ewan, Inouye, Michael, Raff, Jennifer, Rutherford, Adam, and Scally, Aylwyn

Subjects
Quantitative Biology - Populations and Evolution
Abstract

The language commonly used in human genetics can inadvertently pose problems for multiple reasons. Terms like "ancestry", "ethnicity", and other ways of grouping people can have complex, often poorly understood, or multiple meanings within the various fields of genetics, between different domains of biological sciences and medicine, and between scientists and the general public. Furthermore, some categories in frequently used datasets carry scientifically misleading, outmoded or even racist perspectives derived from the history of science. Here, we discuss examples of problematic lexicon in genetics, and how commonly used statistical practices to control for the non-genetic environment may exacerbate difficulties in our terminology, and therefore understanding. Our intention is to stimulate a much-needed discussion about the language of genetics, to begin a process to clarify existing terminology, and in some cases adopt a new lexicon that both serves scientific insight, and cuts us loose from various aspects of a pernicious past.

Published
2021

9. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.

Author

Gharahkhani, Puya, Jorgenson, Eric, Hysi, Pirro, Khawaja, Anthony P, Pendergrass, Sarah, Han, Xikun, Ong, Jue Sheng, Hewitt, Alex W, Segrè, Ayellet V, Rouhana, John M, Hamel, Andrew R, Igo, Robert P, Choquet, Helene, Qassim, Ayub, Josyula, Navya S, Cooke Bailey, Jessica N, Bonnemaijer, Pieter WM, Iglesias, Adriana, Siggs, Owen M, Young, Terri L, Vitart, Veronique, Thiadens, Alberta AHJ, Karjalainen, Juha, Uebe, Steffen, Melles, Ronald B, Nair, K Saidas, Luben, Robert, Simcoe, Mark, Amersinghe, Nishani, Cree, Angela J, Hohn, Rene, Poplawski, Alicia, Chen, Li Jia, Rong, Shi-Song, Aung, Tin, Vithana, Eranga Nishanthie, NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23 and Me Research Team, Tamiya, Gen, Shiga, Yukihiro, Yamamoto, Masayuki, Nakazawa, Toru, Currant, Hannah, Birney, Ewan, Wang, Xin, Auton, Adam, Lupton, Michelle K, Martin, Nicholas G, Ashaye, Adeyinka, Olawoye, Olusola, Williams, Susan E, Akafo, Stephen, Ramsay, Michele, Hashimoto, Kazuki, Kamatani, Yoichiro, Akiyama, Masato, Momozawa, Yukihide, Foster, Paul J, Khaw, Peng T, Morgan, James E, Strouthidis, Nicholas G, Kraft, Peter, Kang, Jae H, Pang, Chi Pui, Pasutto, Francesca, Mitchell, Paul, Lotery, Andrew J, Palotie, Aarno, van Duijn, Cornelia, Haines, Jonathan L, Hammond, Chris, Pasquale, Louis R, Klaver, Caroline CW, Hauser, Michael, Khor, Chiea Chuen, Mackey, David A, Kubo, Michiaki, Cheng, Ching-Yu, Craig, Jamie E, MacGregor, Stuart, and Wiggs, Janey L

Subjects
NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, and Me Research Team, Humans, Glaucoma, Open-Angle, Genetic Predisposition to Disease, Genotype, Polymorphism, Single Nucleotide, Asian Continental Ancestry Group, European Continental Ancestry Group, Genome-Wide Association Study, Genetic Loci, Glaucoma, Open-Angle, Polymorphism, Single Nucleotide
Abstract

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

Published
2021

10. A Simple Reduction for Full-Permuted Pattern Matching Problems on Multi-Track Strings

Author

Barton, Carl, Birney, Ewan, and Fitzgerald, Tomas

Subjects
Computer Science - Data Structures and Algorithms
Abstract

In this paper we study a variant of string pattern matching which deals with tuples of strings known as \textit{multi-track strings}. Multi-track strings are a generalisation of strings (or \textit{single-track strings}) that have primarily found uses in problems related to searching multiple genomes and music information retrieval. A multi-track string $\mathcal{T} = (t_1, t_2, t_3, \ldots , t_N)$ of length $n$ and track count $N$ is a multi-set of $N$ strings of length $n$ with characters drawn from a common alphabet of size $\sigma_U$. Given two multi-track strings $\mathcal{T} = (t_1, t_2, t_3, \ldots , t_N)$ and $ \mathcal{P} = (p_1, p_2, p_3, \ldots , p_N)$ of length $n$ and track count $N$, there is a \textit{full-permuted-match} between $\mathcal{P}$ and $\mathcal{T}$ if $t_{r_i} = p_i$ for all $i \in \{1,2,3,\ldots N \}$ and some permutation $(r_1, r_2, r_3\ldots,r_N)$ of $(1, 2, 3,\ldots,N)$, we denote this $\mathcal{P}\asymp\mathcal{T}$. Efficient algorithms for some full-permuted-match problems on multi-track strings have recently been presented. In this paper we show a reduction from a multi-track string of length $n$ and track count $N$ with alphabet size $\sigma_U$, to a single-track string of length $2n-1$ with alphabet size $\sigma_U^N$. Through this reduction we allow any string algorithm to be used on multi-track string problems using $\asymp$ as the match relation. For polynomial time algorithms on single-track strings of length $n$ there is a multiplicative penalty of not more than $\mathcal{O}(N)$-time for the same algorithm on mt-strings of length $n$ and track count $N$., Comment: Basic error made in lemma on sorting suffixes

Published
2019

16. A joint NCBI and EMBL-EBI transcript set for clinical genomics and research

Author

Morales, Joannella, Pujar, Shashikant, Loveland, Jane E., Astashyn, Alex, Bennett, Ruth, Berry, Andrew, Cox, Eric, Davidson, Claire, Ermolaeva, Olga, Farrell, Catherine M., Fatima, Reham, Gil, Laurent, Goldfarb, Tamara, Gonzalez, Jose M., Haddad, Diana, Hardy, Matthew, Hunt, Toby, Jackson, John, Joardar, Vinita S., Kay, Michael, Kodali, Vamsi K., McGarvey, Kelly M., McMahon, Aoife, Mudge, Jonathan M., Murphy, Daniel N., Murphy, Michael R., Rajput, Bhanu, Rangwala, Sanjida H., Riddick, Lillian D., Thibaud-Nissen, Françoise, Threadgold, Glen, Vatsan, Anjana R., Wallin, Craig, Webb, David, Flicek, Paul, Birney, Ewan, Pruitt, Kim D., Frankish, Adam, Cunningham, Fiona, and Murphy, Terence D.

Published
2022
Full Text
View/download PDF

17. Public archives for biological image data

Author

Ellenberg, Jan, Swedlow, Jason R, Barlow, Mary, Cook, Charles E, Patwardhan, Ardan, Brazma, Alvis, and Birney, Ewan

Subjects
Quantitative Biology - Quantitative Methods
Abstract

Public data archives are the backbone of modern biological and biomedical research. While archives for biological molecules and structures are well-established, resources for imaging data do not yet cover the full range of spatial and temporal scales or application domains used by the scientific community. In the last few years, the technical barriers to building such resources have been solved and the first examples of scientific outputs from public image data resources, often through linkage to existing molecular resources, have been published. Using the successes of existing biomolecular resources as a guide, we present the rationale and principles for the construction of image data archives and databases that will be the foundation of the next revolution in biological and biomedical informatics and discovery., Comment: 13 pages, 1 figure

Published
2018
Full Text
View/download PDF

19. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Abbasizanjani, Hoda, Ahmed, Nida, Ahmed, Badar, Akbari, Ashley, Akinoso-Imran, Abdul Qadr, Allara, Elias, Allery, Freya, Angelantonio, Emanuele Di, Ashworth, Mark, Ayyar-Gupta, Vandana, Babu-Narayan, Sonya, Bacon, Seb, Ball, Steve, Banerjee, Ami, Barber, Mark, Barrett, Jessica, Bennie, Marion, Berry, Colin, Beveridge, Jennifer, Birney, Ewan, Bojanić, Lana, Bolton, Thomas, Bone, Anna, Boyle, Jon, Braithwaite, Tasanee, Bray, Ben, Briffa, Norman, Brind, David, Brown, Katherine, Buch, Maya, Canoy, Dexter, Caputo, Massimo, Carragher, Raymond, Carson, Alan, Cezard, Genevieve, Chang, Jen-Yu Amy, Cheema, Kate, Chin, Richard, Chudasama, Yogini, Cooper, Jennifer, Copland, Emma, Crallan, Rebecca, Cripps, Rachel, Cromwell, David, Curcin, Vasa, Curry, Gwenetta, Dale, Caroline, Danesh, John, Das-Munshi, Jayati, Dashtban, Ashkan, Davies, Alun, Davies, Joanna, Davies, Gareth, Davies, Neil, Day, Joshua, Delmestri, Antonella, Denaxas, Spiros, Denholm, Rachel, Dennis, John, Denniston, Alastair, Deo, Salil, Dhillon, Baljean, Docherty, Annemarie, Dong, Tim, Douiri, Abdel, Downs, Johnny, Dregan, Alexandru, Ellins, Elizabeth A, Elwenspoek, Martha, Falck, Fabian, Falter, Florian, Fan, Yat Yi, Firth, Joseph, Fraser, Lorna, Friebel, Rocco, Gavrieli, Amir, Gerstung, Moritz, Gilbert, Ruth, Gillies, Clare, Glickman, Myer, Goldacre, Ben, Goldacre, Raph, Greaves, Felix, Green, Mark, Grieco, Luca, Griffiths, Rowena, Gurdasani, Deepti, Halcox, Julian, Hall, Nick, Hama, Tuankasfee, Handy, Alex, Hansell, Anna, Hardelid, Pia, Hardy, Flavien, Harris, Daniel, Harrison, Camille, Harron, Katie, Hassaine, Abdelaali, Hassan, Lamiece, Healey, Russell, Hemingway, Harry, Henderson, Angela, Herz, Naomi, Heyl, Johannes, Hidajat, Mira, Higginson, Irene, Hinchliffe, Rosie, Hippisley-Cox, Julia, Ho, Frederick, Hocaoglu, Mevhibe, Hollings, Sam, Horne, Elsie, Hughes, David, Humberstone, Ben, Inouye, Mike, Ip, Samantha, Islam, Nazrul, Jackson, Caroline, Jenkins, David, Jiang, Xiyun, Johnson, Shane, Kadam, Umesh, Kallis, Costas, Karim, Zainab, Kasan, Jake, Katsoulis, Michalis, Kavanagh, Kim, Kee, Frank, Keene, Spencer, Kent, Seamus, Khalid, Sara, Khawaja, Anthony, Khunti, Kamlesh, Killick, Richard, Kinnear, Deborah, Knight, Rochelle, Kolamunnage-Dona, Ruwanthi, Kontopantelis, Evan, Kurdi, Amanj, Lacey, Ben, Lai, Alvina, Lambarth, Andrew, Larzjan, Milad Nazarzadeh, Lawler, Deborah, Lawrence, Thomas, Lawson, Claire, Li, Qiuju, Li, Ken, Llinares, Miguel Bernabeu, Lorgelly, Paula, Lowe, Deborah, Lyons, Jane, Lyons, Ronan, Machado, Pedro, Macleod, Mary Joan, Macleod, John, Malgapo, Evaleen, Mamas, Mamas, Mamouei, Mohammad, Manohar, Sinduja, Mapeta, Rutendo, Martelli, Javiera Leniz, Martos, David Moreno, Mateen, Bilal, McCarthy, Aoife, Melville, Craig, Milton, Rebecca, Mizani, Mehrdad, Moncusi, Marta Pineda, Morales, Daniel, Mordi, Ify, Morrice, Lynn, Morris, Carole, Morris, Eva, Mu, Yi, Mueller, Tanja, Murdock, Lars, Nafilyan, Vahé, Nicholson, George, Nikiphorou, Elena, Nolan, John, Norris, Tom, Norris, Ruth, North, Laura, North, Teri-Louise, O'Connell, Dan, Oliver, Dominic, Oluyase, Adejoke, Olvera-Barrios, Abraham, Omigie, Efosa, Onida, Sarah, Padmanabhan, Sandosh, Palmer, Tom, Pasea, Laura, Patel, Riyaz, Payne, Rupert, Pell, Jill, Petitjean, Carmen, Pherwani, Arun, Pickrell, Owen, Pierotti, Livia, Pirmohamed, Munir, Priedon, Rouven, Prieto-Alhambra, Dani, Proudfoot, Alastair, Quinn, Terry, Quint, Jennifer, Raffetti, Elena, Rahimi, Kazem, Rao, Shishir, Razieh, Cameron, Roberts, Brian, Rogers, Caroline, Rossdale, Jennifer, Salim, Safa, Samani, Nilesh, Sattar, Naveed, Schnier, Christian, Schwartz, Roy, Selby, David, Seminog, Olena, Shabnam, Sharmin, Shah, Ajay, Shelton, Jon, Sheppard, James, Sinha, Shubhra, Skrypak, Mirek, Slapkova, Martina, Sleeman, Katherine, Smith, Craig, Sofat, Reecha, Sosenko, Filip, Sperrin, Matthew, Steeg, Sarah, Sterne, Jonathan, Stoica, Serban, Sudell, Maria, Sudlow, Cathie, Sun, Luanluan, Suseeladevi, Arun Karthikeyan, Sweeting, Michael, Sydes, Matt, Takhar, Rohan, Tang, Howard, Thygesen, Johan, Tilston, George, Tochel, Claire, Toit, Clea du, Tomlinson, Christopher, Toms, Renin, Torabi, Fatemeh, Torralbo, Ana, Townson, Julia, Tufail, Adnan, Tungamirai, Tapiwa, Varma, Susheel, Vollmer, Sebastian, Walker, Venexia, Wang, Tianxiao, Wang, Huan, Warwick, Alasdair, Watkinson, Ruth, Watson, Harry, Whiteley, William, Whittaker, Hannah, Wilde, Harry, Wilkinson, Tim, Williams, Gareth, Williams, Michelle, Williams, Richard, Withnell, Eloise, Wolfe, Charles, Wood, Angela, Wright, Lucy, Wu, Honghan, Wu, Jinge, Wu, Jianhua, Yates, Tom, Zaccardi, Francesco, Zhang, Haoting, Zhang, Huayu, Zuccolo, Luisa, Thygesen, Johan H, Mizani, Mehrdad A, Banerjee, Amitava, Lai, Alvina G, Li, Kezhi, Mateen, Bilal A, Sterne, Jonathan A C, Pagel, Christina, and Whiteley, William N

Published
2022
Full Text
View/download PDF

21. Genomic variations and epigenomic landscape of the Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel

Author

Leger, Adrien, Brettell, Ian, Monahan, Jack, Barton, Carl, Wolf, Nadeshda, Kusminski, Natalja, Herder, Cathrin, Aadepu, Narendar, Becker, Clara, Gierten, Jakob, Hammouda, Omar T., Hasel, Eva, Lischik, Colin, Lust, Katharina, Sokolova, Natalia, Suzuki, Risa, Tavhelidse, Tinatini, Thumberger, Thomas, Tsingos, Erika, Watson, Philip, Welz, Bettina, Naruse, Kiyoshi, Loosli, Felix, Wittbrodt, Joachim, Birney, Ewan, and Fitzgerald, Tomas

Published
2022
Full Text
View/download PDF

22. The Medaka Inbred Kiyosu-Karlsruhe (MIKK) panel

Author

Fitzgerald, Tomas, Brettell, Ian, Leger, Adrien, Wolf, Nadeshda, Kusminski, Natalja, Monahan, Jack, Barton, Carl, Herder, Cathrin, Aadepu, Narendar, Gierten, Jakob, Becker, Clara, Hammouda, Omar T., Hasel, Eva, Lischik, Colin, Lust, Katharina, Sokolova, Natalia, Suzuki, Risa, Tsingos, Erika, Tavhelidse, Tinatini, Thumberger, Thomas, Watson, Philip, Welz, Bettina, Khouja, Nadia, Naruse, Kiyoshi, Birney, Ewan, Wittbrodt, Joachim, and Loosli, Felix

Published
2022
Full Text
View/download PDF

23. Genomic reconstruction of the SARS-CoV-2 epidemic in England

Author

Vöhringer, Harald S., Sanderson, Theo, Sinnott, Matthew, De Maio, Nicola, Nguyen, Thuy, Goater, Richard, Schwach, Frank, Harrison, Ian, Hellewell, Joel, Ariani, Cristina V., Gonçalves, Sonia, Jackson, David K., Johnston, Ian, Jung, Alexander W., Saint, Callum, Sillitoe, John, Suciu, Maria, Goldman, Nick, Panovska-Griffiths, Jasmina, Birney, Ewan, Volz, Erik, Funk, Sebastian, Kwiatkowski, Dominic, Chand, Meera, Martincorena, Inigo, Barrett, Jeffrey C., and Gerstung, Moritz

Published
2021
Full Text
View/download PDF

24. REMBI: Recommended Metadata for Biological Images—enabling reuse of microscopy data in biology

Author

Sarkans, Ugis, Chiu, Wah, Collinson, Lucy, Darrow, Michele C., Ellenberg, Jan, Grunwald, David, Hériché, Jean-Karim, Iudin, Andrii, Martins, Gabriel G., Meehan, Terry, Narayan, Kedar, Patwardhan, Ardan, Russell, Matthew Robert Geoffrey, Saibil, Helen R., Strambio-De-Castillia, Caterina, Swedlow, Jason R., Tischer, Christian, Uhlmann, Virginie, Verkade, Paul, Barlow, Mary, Bayraktar, Omer, Birney, Ewan, Catavitello, Cesare, Cawthorne, Christopher, Wagner-Conrad, Stephan, Duke, Elizabeth, Paul-Gilloteaux, Perrine, Gustin, Emmanuel, Harkiolaki, Maria, Kankaanpää, Pasi, Lemberger, Thomas, McEntyre, Jo, Moore, Josh, Nicholls, Andrew W., Onami, Shuichi, Parkinson, Helen, Parsons, Maddy, Romanchikova, Marina, Sofroniew, Nicholas, Swoger, Jim, Utz, Nadine, Voortman, Lenard M., Wong, Frances, Zhang, Peijun, Kleywegt, Gerard J., and Brazma, Alvis

Published
2021
Full Text
View/download PDF

25. The Human Cell Atlas.

Author

Regev, Aviv, Teichmann, Sarah A, Lander, Eric S, Amit, Ido, Benoist, Christophe, Birney, Ewan, Bodenmiller, Bernd, Campbell, Peter, Carninci, Piero, Clatworthy, Menna, Clevers, Hans, Deplancke, Bart, Dunham, Ian, Eberwine, James, Eils, Roland, Enard, Wolfgang, Farmer, Andrew, Fugger, Lars, Göttgens, Berthold, Hacohen, Nir, Haniffa, Muzlifah, Hemberg, Martin, Kim, Seung, Klenerman, Paul, Kriegstein, Arnold, Lein, Ed, Linnarsson, Sten, Lundberg, Emma, Lundeberg, Joakim, Majumder, Partha, Marioni, John C, Merad, Miriam, Mhlanga, Musa, Nawijn, Martijn, Netea, Mihai, Nolan, Garry, Pe'er, Dana, Phillipakis, Anthony, Ponting, Chris P, Quake, Stephen, Reik, Wolf, Rozenblatt-Rosen, Orit, Sanes, Joshua, Satija, Rahul, Schumacher, Ton N, Shalek, Alex, Shapiro, Ehud, Sharma, Padmanee, Shin, Jay W, Stegle, Oliver, Stratton, Michael, Stubbington, Michael JT, Theis, Fabian J, Uhlen, Matthias, van Oudenaarden, Alexander, Wagner, Allon, Watt, Fiona, Weissman, Jonathan, Wold, Barbara, Xavier, Ramnik, Yosef, Nir, and Human Cell Atlas Meeting Participants

Subjects
Human Cell Atlas Meeting Participants, Eukaryotic Cells, Humans, Human Body, International Cooperation, Atlases as Topic, cell atlas, cell biology, computational biology, human, lineage, mouse, science forum, single-cell genomics, systems biology, Biochemistry and Cell Biology
Abstract

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

Published
2017

26. GA4GH: International policies and standards for data sharing across genomic research and healthcare

Author

Rehm, Heidi L., Page, Angela J.H., Smith, Lindsay, Adams, Jeremy B., Alterovitz, Gil, Babb, Lawrence J., Barkley, Maxmillian P., Baudis, Michael, Beauvais, Michael J.S., Beck, Tim, Beckmann, Jacques S., Beltran, Sergi, Bernick, David, Bernier, Alexander, Bonfield, James K., Boughtwood, Tiffany F., Bourque, Guillaume, Bowers, Sarion R., Brookes, Anthony J., Brudno, Michael, Brush, Matthew H., Bujold, David, Burdett, Tony, Buske, Orion J., Cabili, Moran N., Cameron, Daniel L., Carroll, Robert J., Casas-Silva, Esmeralda, Chakravarty, Debyani, Chaudhari, Bimal P., Chen, Shu Hui, Cherry, J. Michael, Chung, Justina, Cline, Melissa, Clissold, Hayley L., Cook-Deegan, Robert M., Courtot, Mélanie, Cunningham, Fiona, Cupak, Miro, Davies, Robert M., Denisko, Danielle, Doerr, Megan J., Dolman, Lena I., Dove, Edward S., Dursi, L. Jonathan, Dyke, Stephanie O.M., Eddy, James A., Eilbeck, Karen, Ellrott, Kyle P., Fairley, Susan, Fakhro, Khalid A., Firth, Helen V., Fitzsimons, Michael S., Fiume, Marc, Flicek, Paul, Fore, Ian M., Freeberg, Mallory A., Freimuth, Robert R., Fromont, Lauren A., Fuerth, Jonathan, Gaff, Clara L., Gan, Weiniu, Ghanaim, Elena M., Glazer, David, Green, Robert C., Griffith, Malachi, Griffith, Obi L., Grossman, Robert L., Groza, Tudor, Guidry Auvil, Jaime M., Guigó, Roderic, Gupta, Dipayan, Haendel, Melissa A., Hamosh, Ada, Hansen, David P., Hart, Reece K., Hartley, Dean Mitchell, Haussler, David, Hendricks-Sturrup, Rachele M., Ho, Calvin W.L., Hobb, Ashley E., Hoffman, Michael M., Hofmann, Oliver M., Holub, Petr, Hsu, Jacob Shujui, Hubaux, Jean-Pierre, Hunt, Sarah E., Husami, Ammar, Jacobsen, Julius O., Jamuar, Saumya S., Janes, Elizabeth L., Jeanson, Francis, Jené, Aina, Johns, Amber L., Joly, Yann, Jones, Steven J.M., Kanitz, Alexander, Kato, Kazuto, Keane, Thomas M., Kekesi-Lafrance, Kristina, Kelleher, Jerome, Kerry, Giselle, Khor, Seik-Soon, Knoppers, Bartha M., Konopko, Melissa A., Kosaki, Kenjiro, Kuba, Martin, Lawson, Jonathan, Leinonen, Rasko, Li, Stephanie, Lin, Michael F., Linden, Mikael, Liu, Xianglin, Liyanage, Isuru Udara, Lopez, Javier, Lucassen, Anneke M., Lukowski, Michael, Mann, Alice L., Marshall, John, Mattioni, Michele, Metke-Jimenez, Alejandro, Middleton, Anna, Milne, Richard J., Molnár-Gábor, Fruzsina, Mulder, Nicola, Munoz-Torres, Monica C., Nag, Rishi, Nakagawa, Hidewaki, Nasir, Jamal, Navarro, Arcadi, Nelson, Tristan H., Niewielska, Ania, Nisselle, Amy, Niu, Jeffrey, Nyrönen, Tommi H., O’Connor, Brian D., Oesterle, Sabine, Ogishima, Soichi, Ota Wang, Vivian, Paglione, Laura A.D., Palumbo, Emilio, Parkinson, Helen E., Philippakis, Anthony A., Pizarro, Angel D., Prlic, Andreas, Rambla, Jordi, Rendon, Augusto, Rider, Renee A., Robinson, Peter N., Rodarmer, Kurt W., Rodriguez, Laura Lyman, Rubin, Alan F., Rueda, Manuel, Rushton, Gregory A., Ryan, Rosalyn S., Saunders, Gary I., Schuilenburg, Helen, Schwede, Torsten, Scollen, Serena, Senf, Alexander, Sheffield, Nathan C., Skantharajah, Neerjah, Smith, Albert V., Sofia, Heidi J., Spalding, Dylan, Spurdle, Amanda B., Stark, Zornitza, Stein, Lincoln D., Suematsu, Makoto, Tan, Patrick, Tedds, Jonathan A., Thomson, Alastair A., Thorogood, Adrian, Tickle, Timothy L., Tokunaga, Katsushi, Törnroos, Juha, Torrents, David, Upchurch, Sean, Valencia, Alfonso, Guimera, Roman Valls, Vamathevan, Jessica, Varma, Susheel, Vears, Danya F., Viner, Coby, Voisin, Craig, Wagner, Alex H., Wallace, Susan E., Walsh, Brian P., Williams, Marc S., Winkler, Eva C., Wold, Barbara J., Wood, Grant M., Woolley, J. Patrick, Yamasaki, Chisato, Yates, Andrew D., Yung, Christina K., Zass, Lyndon J., Zaytseva, Ksenia, Zhang, Junjun, Goodhand, Peter, North, Kathryn, and Birney, Ewan

Published
2021
Full Text
View/download PDF

27. Highly accurate protein structure prediction for the human proteome

Author

Tunyasuvunakool, Kathryn, Adler, Jonas, Wu, Zachary, Green, Tim, Zielinski, Michal, Žídek, Augustin, Bridgland, Alex, Cowie, Andrew, Meyer, Clemens, Laydon, Agata, Velankar, Sameer, Kleywegt, Gerard J., Bateman, Alex, Evans, Richard, Pritzel, Alexander, Figurnov, Michael, Ronneberger, Olaf, Bates, Russ, Kohl, Simon A. A., Potapenko, Anna, Ballard, Andrew J., Romera-Paredes, Bernardino, Nikolov, Stanislav, Jain, Rishub, Clancy, Ellen, Reiman, David, Petersen, Stig, Senior, Andrew W., Kavukcuoglu, Koray, Birney, Ewan, Kohli, Pushmeet, Jumper, John, and Hassabis, Demis

Published
2021
Full Text
View/download PDF

31. AlphaFold Protein Structure Database in 2024: providing structure coverage for over 214 million protein sequences

Author

Varadi, Mihaly, primary, Bertoni, Damian, additional, Magana, Paulyna, additional, Paramval, Urmila, additional, Pidruchna, Ivanna, additional, Radhakrishnan, Malarvizhi, additional, Tsenkov, Maxim, additional, Nair, Sreenath, additional, Mirdita, Milot, additional, Yeo, Jingi, additional, Kovalevskiy, Oleg, additional, Tunyasuvunakool, Kathryn, additional, Laydon, Agata, additional, Žídek, Augustin, additional, Tomlinson, Hamish, additional, Hariharan, Dhavanthi, additional, Abrahamson, Josh, additional, Green, Tim, additional, Jumper, John, additional, Birney, Ewan, additional, Steinegger, Martin, additional, Hassabis, Demis, additional, and Velankar, Sameer, additional

Published
2023
Full Text
View/download PDF

32. Integrative analysis of gene expression, DNA methylation, physiological traits, and genetic variation in human skeletal muscle

Author

Taylor, D. Leland, Jackson, Anne U., Narisu, Narisu, Hemani, Gibran, Erdos, Michael R., Chines, Peter S., Swift, Amy, Idol, Jackie, Didion, John P., Welch, Ryan P., Kinnunen, Leena, Saramies, Jouko, Lakka, Timo A., Laakso, Markku, Tuomilehto, Jaakko, Parker, Stephen C. J., Koistinen, Heikki A., Smith, George Davey, Boehnke, Michael, Scott, Laura J., Birney, Ewan, and Collins, Francis S.

Published
2019

33. RNA modifications detection by comparative Nanopore direct RNA sequencing

Author

Leger, Adrien, Amaral, Paulo P., Pandolfini, Luca, Capitanchik, Charlotte, Capraro, Federica, Miano, Valentina, Migliori, Valentina, Toolan-Kerr, Patrick, Sideri, Theodora, Enright, Anton J., Tzelepis, Konstantinos, van Werven, Folkert J., Luscombe, Nicholas M., Barbieri, Isaia, Ule, Jernej, Fitzgerald, Tomas, Birney, Ewan, Leonardi, Tommaso, and Kouzarides, Tony

Published
2021
Full Text
View/download PDF

34. Genetic and functional insights into the fractal structure of the heart

Author

Meyer, Hannah V., Dawes, Timothy J. W., Serrani, Marta, Bai, Wenjia, Tokarczuk, Paweł, Cai, Jiashen, de Marvao, Antonio, Henry, Albert, Lumbers, R. Thomas, Gierten, Jakob, Thumberger, Thomas, Wittbrodt, Joachim, Ware, James S., Rueckert, Daniel, Matthews, Paul M., Prasad, Sanjay K., Costantino, Maria L., Cook, Stuart A., Birney, Ewan, and O’Regan, Declan P.

Published
2020
Full Text
View/download PDF

35. Genomic and phenotypic characterisation of a wild Medaka population: Establishing an isogenic population genetic resource in fish

Author

Spivakov, Mikhail, Auer, Thomas O., Peravali, Ravindra, Dunham, Ian, Dolle, Dirk, Fujiyama, Asao, Toyoda, Atsushi, Aizu, Tomoyuki, Minakuchi, Yohei, Loosli, Felix, Naruse, Kiyoshi, Birney, Ewan, and Wittbrodt, Joachim

Subjects
Quantitative Biology - Genomics, Quantitative Biology - Populations and Evolution
Abstract

Background Oryzias latipes (Medaka) has been established as a vertebrate genetic model for over a century, and has recently been rediscovered outside its native Japan. The power of new sequencing methods now makes it possible to reinvigorate Medaka genetics, in particular by establishing a near-isogenic panel derived from a single wild population. Results Here we characterise the genomes of wild Medaka catches obtained from a single Southern Japanese population in Kiyosu as a precursor for the establishment of a near isogenic panel of wild lines. The population is free of significant detrimental population structure, and has advantageous linkage disequilibrium properties suitable for establishment of the proposed panel. Analysis of morphometric traits in five representative inbred strains suggests phenotypic mapping will be feasible in the panel. In addition high throughput genome sequencing of these Medaka strains confirms their evolutionary relationships on lines of geographic separation and provides further evidence that there has been little significant interbreeding between the Southern and Northern Medaka population since the Southern/Northern population split. The sequence data suggest that the Southern Japanese Medaka existed as a larger older population which went through a relatively recent bottleneck around 10,000 years ago. In addition we detect patterns of recent positive selection in the Southern population. Conclusions These data indicate that the genetic structure of the Kiyosu Medaka samples are suitable for the establishment of a vertebrate near isogenic panel and therefore inbreeding of 200 lines based on this population has commenced. Progress of this project can be tracked at http://www.ebi.ac.uk/birney-srv/medaka-ref-panel, Comment: 5 figures, 30 pages

Published
2013

36. Leveraging European infrastructures to access 1 million human genomes by 2022

Author

Saunders, Gary, Baudis, Michael, Becker, Regina, Beltran, Sergi, Béroud, Christophe, Birney, Ewan, Brooksbank, Cath, Brunak, Søren, Van den Bulcke, Marc, Drysdale, Rachel, Capella-Gutierrez, Salvador, Flicek, Paul, Florindi, Francesco, Goodhand, Peter, Gut, Ivo, Heringa, Jaap, Holub, Petr, Hooyberghs, Jef, Juty, Nick, Keane, Thomas M., Korbel, Jan O., Lappalainen, Ilkka, Leskosek, Brane, Matthijs, Gert, Mayrhofer, Michaela Th., Metspalu, Andres, Navarro, Arcadi, Newhouse, Steven, Nyrönen, Tommi, Page, Angela, Persson, Bengt, Palotie, Aarno, Parkinson, Helen, Rambla, Jordi, Salgado, David, Steinfelder, Erik, Swertz, Morris A., Valencia, Alfonso, Varma, Susheel, Blomberg, Niklas, and Scollen, Serena

Published
2019
Full Text
View/download PDF

37. Publisher Correction: Genomic reconstruction of the SARS CoV-2 epidemic in England

Author

Vöhringer, Harald S., Sanderson, Theo, Sinnott, Matthew, De Maio, Nicola, Nguyen, Thuy, Goater, Richard, Schwach, Frank, Harrison, Ian, Hellewell, Joel, Ariani, Cristina V., Gonçalves, Sonia, Jackson, David K., Johnston, Ian, Jung, Alexander W., Saint, Callum, Sillitoe, John, Suciu, Maria, Goldman, Nick, Panovska-Griffiths, Jasmina, Birney, Ewan, Volz, Erik, Funk, Sebastian, Kwiatkowski, Dominic, Chand, Meera, Martincorena, Inigo, Barrett, Jeffrey C., and Gerstung, Moritz

Published
2022
Full Text
View/download PDF

38. Benchmarking of computational methods for m6A profiling with Nanopore direct RNA sequencing.

Author

Maestri, Simone, Furlan, Mattia, Mulroney, Logan, Tarrero, Lucia Coscujuela, Ugolini, Camilla, Pozza, Fabio Dalla, Leonardi, Tommaso, Birney, Ewan, Nicassio, Francesco, and Pelizzola, Mattia

Subjects
RNA sequencing, RNA modification & restriction, ADENOSINES
Abstract

N6-methyladenosine (m6A) is the most abundant internal eukaryotic mRNA modification, and is involved in the regulation of various biological processes. Direct Nanopore sequencing of native RNA (dRNA-seq) emerged as a leading approach for its identification. Several software were published for m6A detection and there is a strong need for independent studies benchmarking their performance on data from different species, and against various reference datasets. Moreover, a computational workflow is needed to streamline the execution of tools whose installation and execution remains complicated. We developed NanOlympicsMod, a Nextflow pipeline exploiting containerized technology for comparing 14 tools for m6A detection on dRNA-seq data. NanOlympicsMod was tested on dRNA-seq data generated from in vitro (un)modified synthetic oligos. The m6A hits returned by each tool were compared to the m6A position known by design of the oligos. In addition, NanOlympicsMod was used on dRNA-seq datasets from wild-type and m6A-depleted yeast, mouse and human, and each tool's hits were compared to reference m6A sets generated by leading orthogonal methods. The performance of the tools markedly differed across datasets, and methods adopting different approaches showed different preferences in terms of precision and recall. Changing the stringency cut-offs allowed for tuning the precision-recall trade-off towards user preferences. Finally, we determined that precision and recall of tools are markedly influenced by sequencing depth, and that additional sequencing would likely reveal additional m6A sites. Thanks to the possibility of including novel tools, NanOlympicsMod will streamline the benchmarking of m6A detection tools on dRNA-seq data, improving future RNA modification characterization. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

39. AlphaFold Protein Structure Database in 2024: providing structure coverage for over 214 million protein sequences.

Author

Varadi, Mihaly, Bertoni, Damian, Magana, Paulyna, Paramval, Urmila, Pidruchna, Ivanna, Radhakrishnan, Malarvizhi, Tsenkov, Maxim, Nair, Sreenath, Mirdita, Milot, Yeo, Jingi, Kovalevskiy, Oleg, Tunyasuvunakool, Kathryn, Laydon, Agata, Žídek, Augustin, Tomlinson, Hamish, Hariharan, Dhavanthi, Abrahamson, Josh, Green, Tim, Jumper, John, and Birney, Ewan

Published
2024
Full Text
View/download PDF

42. Needed for completion of the human genome: hypothesis driven experiments and biologically realistic mathematical models

Author

Guigo, Roderic, Birney, Ewan, Brent, Michael, Dermitzakis, Emmanouil, Pachter, Lior, Crollius, Hugues Roest, Solovyev, Victor, and Zhang, Michael Q.

Subjects
Quantitative Biology - Genomics
Abstract

With the sponsorship of ``Fundacio La Caixa'' we met in Barcelona, November 21st and 22nd, to analyze the reasons why, after the completion of the human genome sequence, the identification all protein coding genes and their variants remains a distant goal. Here we report on our discussions and summarize some of the major challenges that need to be overcome in order to complete the human gene catalog., Comment: Report and discussion resulting from the `Fundacio La Caixa' gene finding meeting held November 21 and 22 2003 in Barcelona

Published
2004

43. Integrative annotation of chromatin elements from ENCODE data

Author

Hoffman, Michael M, Ernst, Jason, Wilder, Steven P, Kundaje, Anshul, Harris, Robert S, Libbrecht, Max, Giardine, Belinda, Ellenbogen, Paul M, Bilmes, Jeffrey A, Birney, Ewan, Hardison, Ross C, Dunham, Ian, Kellis, Manolis, and Noble, William Stafford

Subjects
Human Genome, Genetics, Generic health relevance, Chromatin, Enhancer Elements, Genetic, Genome, Human, Genome-Wide Association Study, Humans, Insulator Elements, Molecular Sequence Annotation, Promoter Regions, Genetic, Proteins, Regulatory Elements, Transcriptional, Terminator Regions, Genetic, Transcription, Genetic, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Developmental Biology
Abstract

The ENCODE Project has generated a wealth of experimental information mapping diverse chromatin properties in several human cell lines. Although each such data track is independently informative toward the annotation of regulatory elements, their interrelations contain much richer information for the systematic annotation of regulatory elements. To uncover these interrelations and to generate an interpretable summary of the massive datasets of the ENCODE Project, we apply unsupervised learning methodologies, converting dozens of chromatin datasets into discrete annotation maps of regulatory regions and other chromatin elements across the human genome. These methods rediscover and summarize diverse aspects of chromatin architecture, elucidate the interplay between chromatin activity and RNA transcription, and reveal that a large proportion of the genome lies in a quiescent state, even across multiple cell types. The resulting annotation of non-coding regulatory elements correlate strongly with mammalian evolutionary constraint, and provide an unbiased approach for evaluating metrics of evolutionary constraint in human. Lastly, we use the regulatory annotations to revisit previously uncharacterized disease-associated loci, resulting in focused, testable hypotheses through the lens of the chromatin landscape.

Published
2013

44. A Maturity Level Model (MLM) for the self-assessment of genomic medicine practices in healthcare systems

Author

Cardoso, maria Luis, Lopes, Fatima, Costa, Alexandra, Santos, Osvaldo, Konopko, Melissa, Merchant, Arshiya, Thorogood, Adrian, Saunders, Gary, Custers, Ilse, Bulcke, Marc Van Den, Schmitt, Tugce, Bogicevic, Ivana, Cividanes, Lene, Spalding, Dylan, Smith, Maeve, Bale, Mark, Pitini, Erica, Villari, Paolo, Baccolini, Valentina, Balciuniene, Anzelika, Ambrozaityte, Laima, Doménech, Elena, Martin-Sanchez, Fernando, Sobrón, Francisco, Saiz, Maria Luisa, Carracedo, Angel, Wedell, Anna, Thomsen, Anne Cambon, Veimer, Annika, Lundgren, Bettina, Solary, Eric, Birney, Ewan, Martins, Henrique, Klovins, Janis, Saarela, Janna, North, Kathryn, Caulfield, Mark, Piha, Tapani, Scollen, Serena, and Vicente, Astrid

Subjects
1+MG, genomics, Beyond 1M Genomes, Genome of Europe
Abstract

Genomic medicine implementation in healthcare systems can bring us one step closer to making personalised medicine a reality, with major socioeconomic benefits. Citizens and patients canwidely benefit from genomic data analysis for accurate and timely diagnosis, effective treatments with less adverse events, and accurate profiling for disease prevention. Implementation of genomics in healthcare is complex and requires adjustments in the governance, structure and organization of health services, as well as dedicated investments. Implementation is also dependent on the country context. In the context of the 1+Million Genomes (1+MG) initiative, we developed a Maturity Level Model (MLM) for health systems to self-evaluate the maturity of their genomic medicine practices, and define a path to optimization. MLM is a tool for healthcare systems to self-evaluate the level of maturity of their genomic medicine practices according to a common matrix, and to define a path to optimization. A MLM pilot in eight European countries provided important information regarding common strengths, weaknesses and asymmetries across Europe.

Published
2023
Full Text
View/download PDF

46. Classification of human genomic regions based on experimentally determined binding sites of more than 100 transcription-related factors

Author

Yip, Kevin Y, Cheng, Chao, Bhardwaj, Nitin, Brown, James B, Leng, Jing, Kundaje, Anshul, Rozowsky, Joel, Birney, Ewan, Bickel, Peter, Snyder, Michael, and Gerstein, Mark

Abstract

Abstract Background Transcription factors function by binding different classes of regulatory elements. The Encyclopedia of DNA Elements (ENCODE) project has recently produced binding data for more than 100 transcription factors from about 500 ChIP-seq experiments in multiple cell types. While this large amount of data creates a valuable resource, it is nonetheless overwhelmingly complex and simultaneously incomplete since it covers only a small fraction of all human transcription factors. Results As part of the consortium effort in providing a concise abstraction of the data for facilitating various types of downstream analyses, we constructed statistical models that capture the genomic features of three paired types of regions by machine-learning methods: firstly, regions with active or inactive binding; secondly, those with extremely high or low degrees of co-binding, termed HOT and LOT regions; and finally, regulatory modules proximal or distal to genes. From the distal regulatory modules, we developed computational pipelines to identify potential enhancers, many of which were validated experimentally. We further associated the predicted enhancers with potential target transcripts and the transcription factors involved. For HOT regions, we found a significant fraction of transcription factor binding without clear sequence motifs and showed that this observation could be related to strong DNA accessibility of these regions. Conclusions Overall, the three pairs of regions exhibit intricate differences in chromosomal locations, chromatin features, factors that bind them, and cell-type specificity. Our machine learning approach enables us to identify features potentially general to all transcription factors, including those not included in the data.

Published
2012

47. The genomic basis of adaptive evolution in threespine sticklebacks.

Author

Jones, Felicity C, Grabherr, Manfred G, Chan, Yingguang Frank, Russell, Pamela, Mauceli, Evan, Johnson, Jeremy, Swofford, Ross, Pirun, Mono, Zody, Michael C, White, Simon, Birney, Ewan, Searle, Stephen, Schmutz, Jeremy, Grimwood, Jane, Dickson, Mark C, Myers, Richard M, Miller, Craig T, Summers, Brian R, Knecht, Anne K, Brady, Shannon D, Zhang, Haili, Pollen, Alex A, Howes, Timothy, Amemiya, Chris, Broad Institute Genome Sequencing Platform & Whole Genome Assembly Team, Baldwin, Jen, Bloom, Toby, Jaffe, David B, Nicol, Robert, Wilkinson, Jane, Lander, Eric S, Di Palma, Federica, Lindblad-Toh, Kerstin, and Kingsley, David M

Subjects
Broad Institute Genome Sequencing Platform & Whole Genome Assembly Team, Chromosomes, Animals, Smegmamorpha, Sequence Analysis, DNA, Genomics, Fresh Water, Seawater, Adaptation, Physiological, Conserved Sequence, Genome, Molecular Sequence Data, Alaska, Female, Genetic Variation, Chromosome Inversion, Biological Evolution, Aquatic Organisms, Ecotype, General Science & Technology
Abstract

Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine-freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine-freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.

Published
2012

48. A high-resolution map of human evolutionary constraint using 29 mammals.

Author

Lindblad-Toh, Kerstin, Garber, Manuel, Zuk, Or, Lin, Michael F, Parker, Brian J, Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Jordan, Gregory, Mauceli, Evan, Ward, Lucas D, Lowe, Craig B, Holloway, Alisha K, Clamp, Michele, Gnerre, Sante, Alföldi, Jessica, Beal, Kathryn, Chang, Jean, Clawson, Hiram, Cuff, James, Di Palma, Federica, Fitzgerald, Stephen, Flicek, Paul, Guttman, Mitchell, Hubisz, Melissa J, Jaffe, David B, Jungreis, Irwin, Kent, W James, Kostka, Dennis, Lara, Marcia, Martins, Andre L, Massingham, Tim, Moltke, Ida, Raney, Brian J, Rasmussen, Matthew D, Robinson, Jim, Stark, Alexander, Vilella, Albert J, Wen, Jiayu, Xie, Xiaohui, Zody, Michael C, Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baldwin, Jen, Bloom, Toby, Chin, Chee Whye, Heiman, Dave, Nicol, Robert, Nusbaum, Chad, Young, Sarah, Wilkinson, Jane, Worley, Kim C, Kovar, Christie L, Muzny, Donna M, Gibbs, Richard A, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Cree, Andrew, Dihn, Huyen H, Fowler, Gerald, Jhangiani, Shalili, Joshi, Vandita, Lee, Sandra, Lewis, Lora R, Nazareth, Lynne V, Okwuonu, Geoffrey, Santibanez, Jireh, Warren, Wesley C, Mardis, Elaine R, Weinstock, George M, Wilson, Richard K, Genome Institute at Washington University, Delehaunty, Kim, Dooling, David, Fronik, Catrina, Fulton, Lucinda, Fulton, Bob, Graves, Tina, Minx, Patrick, Sodergren, Erica, Birney, Ewan, Margulies, Elliott H, Herrero, Javier, Green, Eric D, Haussler, David, Siepel, Adam, Goldman, Nick, Pollard, Katherine S, Pedersen, Jakob S, Lander, Eric S, and Kellis, Manolis

Subjects
Broad Institute Sequencing Platform and Whole Genome Assembly Team, Baylor College of Medicine Human Genome Sequencing Center Sequencing Team, Genome Institute at Washington University, Animals, Mammals, Humans, Disease, RNA, Sequence Alignment, Sequence Analysis, DNA, Genomics, Evolution, Molecular, Phylogeny, Genome, Genome, Human, Exons, Health, Selection, Genetic, Molecular Sequence Annotation, Sequence Analysis, DNA, Evolution, Molecular, Human, Selection, Genetic, General Science & Technology
Abstract

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

Published
2011

49. Sub-cellular level resolution of common genetic variation in the photoreceptor layer identifies continuum between rare disease and common variation

Author

Currant, Hannah, Fitzgerald, Tomas W, Patel, Praveen J, Khawaja, Anthony P, UK Biobank Eye And Vision Consortium, Webster, Andrew R, Mahroo, Omar A, Birney, Ewan, Currant, Hannah [0000-0003-2764-6787], Patel, Praveen J [0000-0001-8682-4067], Khawaja, Anthony P [0000-0001-6802-8585], Mahroo, Omar A [0000-0003-1254-0832], Birney, Ewan [0000-0001-8314-8497], and Apollo - University of Cambridge Repository

Subjects
Rare Diseases, Humans, Genetic Variation, Photoreceptor Cells, Retina, Genome-Wide Association Study
Abstract

Acknowledgements: The authors are extremely grateful for the selfless participation of individuals in the UK Biobank used in this study and the staff managing these cohorts., Funder: EMBL, Funder: UKRI Future Leaders Fellowship, Funder: Alcon Young Investigator Award, Photoreceptor cells (PRCs) are the light-detecting cells of the retina. Such cells can be non-invasively imaged using optical coherence tomography (OCT) which is used in clinical settings to diagnose and monitor ocular diseases. Here we present the largest genome-wide association study of PRC morphology to date utilising quantitative phenotypes extracted from OCT images within the UK Biobank. We discovered 111 loci associated with the thickness of one or more of the PRC layers, many of which had prior associations to ocular phenotypes and pathologies, and 27 with no prior associations. We further identified 10 genes associated with PRC thickness through gene burden testing using exome data. In both cases there was a significant enrichment for genes involved in rare eye pathologies, in particular retinitis pigmentosa. There was evidence for an interaction effect between common genetic variants, VSX2 involved in eye development and PRPH2 known to be involved in retinal dystrophies. We further identified a number of genetic variants with a differential effect across the macular spatial field. Our results suggest a continuum between common and rare variation which impacts retinal structure, sometimes leading to disease.

Published
2023
Full Text
View/download PDF

50. A Survey of Homozygous Deletions in Human Cancer Genomes

Author

Cox, Charles, Bignell, Graham, Greenman, Chris, Stabenau, Arne, Warren, William, Stephens, Philip, Davies, Helen, Watt, Stephen, Teague, Jon, Edkins, Sara, Birney, Ewan, Easton, Douglas F., Wooster, Richard, Futreal, P. Andrew, Stratton, Michael R., and Vogelstein, Bert

Published
2005

Catalog

Books, media, physical & digital resources
See catalog results