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12. EcoFABs: advancing microbiome science through standardized fabricated ecosystems

Author

Zengler, Karsten, Hofmockel, Kirsten, Baliga, Nitin S., Behie, Scott W., Bernstein, Hans C., Brown, James B., Dinneny, José R., Floge, Sheri A., Forry, Samuel P., Hess, Matthias, Jackson, Scott A., Jansson, Christer, Lindemann, Stephen R., Pett-Ridge, Jennifer, Maranas, Costas, Venturelli, Ophelia S., Wallenstein, Matthew D., Shank, Elizabeth A., and Northen, Trent R.

Published
2019
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13. 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

17. Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions

Author

MacArthur, Stewart, Li, Xiao-Yong, Li, Jingyi, Brown, James B, Chu, Hou Cheng, Zeng, Lucy, Grondona, Brandi P, Hechmer, Aaron, Simirenko, Lisa, Keränen, Soile VE, Knowles, David W, Stapleton, Mark, Bickel, Peter, Biggin, Mark D, and Eisen, Michael B

Abstract

Abstract Background We previously established that six sequence-specific transcription factors that initiate anterior/posterior patterning in Drosophila bind to overlapping sets of thousands of genomic regions in blastoderm embryos. While regions bound at high levels include known and probable functional targets, more poorly bound regions are preferentially associated with housekeeping genes and/or genes not transcribed in the blastoderm, and are frequently found in protein coding sequences or in less conserved non-coding DNA, suggesting that many are likely non-functional. Results Here we show that an additional 15 transcription factors that regulate other aspects of embryo patterning show a similar quantitative continuum of function and binding to thousands of genomic regions in vivo. Collectively, the 21 regulators show a surprisingly high overlap in the regions they bind given that they belong to 11 DNA binding domain families, specify distinct developmental fates, and can act via different cis-regulatory modules. We demonstrate, however, that quantitative differences in relative levels of binding to shared targets correlate with the known biological and transcriptional regulatory specificities of these factors. Conclusions It is likely that the overlap in binding of biochemically and functionally unrelated transcription factors arises from the high concentrations of these proteins in nuclei, which, coupled with their broad DNA binding specificities, directs them to regions of open chromatin. We suggest that most animal transcription factors will be found to show a similar broad overlapping pattern of binding in vivo, with specificity achieved by modulating the amount, rather than the identity, of bound factor.

Published
2009

24. Downscaled hyper-resolution (400 m) gridded datasets of daily precipitation and temperature (2008–2019) for the East–Taylor subbasin (western United States).

Author

Mital, Utkarsh, Dwivedi, Dipankar, Brown, James B., and Steefel, Carl I.

Subjects
WATER security, SPATIAL resolution, WATERSHEDS, TEMPERATURE, DOWNSCALING (Climatology)
Abstract

High-resolution gridded datasets of meteorological variables are needed in order to resolve fine-scale hydrological gradients in complex mountainous terrain. Across the United States, the highest available spatial resolution of gridded datasets of daily meteorological records is approximately 800 m. This work presents gridded datasets of daily precipitation and mean temperature for the East–Taylor subbasin (in the western United States) covering a 12-year period (2008–2019) at a high spatial resolution (400 m). The datasets are generated using a downscaling framework that uses data-driven models to learn relationships between climate variables and topography. We observe that downscaled datasets of precipitation and mean temperature exhibit smoother spatial gradients (while preserving the spatial variability) when compared to their coarser counterparts. Additionally, we also observe that when downscaled datasets are upscaled to the original resolution (800 m), the mean residual error is almost zero, ensuring no bias when compared with the original data. Furthermore, the downscaled datasets are observed to be linearly related to elevation, which is consistent with the methodology underlying the original 800 m product. Finally, we validate the spatial patterns exhibited by downscaled datasets via an example use case that models lidar-derived estimates of snowpack. The presented dataset constitutes a valuable resource to resolve fine-scale hydrological gradients in the mountainous terrain of the East–Taylor subbasin, which is an important study area in the context of water security for the southwestern United States and Mexico. The dataset is publicly available at 10.15485/1822259 (Mital et al., 2021). [ABSTRACT FROM AUTHOR]

Published
2022
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27. An integrated encyclopedia of DNA elements in the human genome

Author

Dunham, Ian, Kundaje, Anshul, Aldred, Shelley F., Collins, Patrick J., Davis, Carrie A., Doyle, Francis, Epstein, Charles B., Frietze, Seth, Harrow, Jennifer, Kaul, Rajinder, Khatun, Jainab, Lajoie, Bryan R., Landt, Stephen G., Lee, Bum-Kyu, Pauli, Florencia, Rosenbloom, Kate R., Sabo, Peter, Safi, Alexias, Sanyal, Amartya, Shoresh, Noam, Simon, Jeremy M., Song, Lingyun, Trinklein, Nathan D., Altshuler, Robert C., Birney, Ewan, Brown, James B., Cheng, Chao, Djebali, Sarah, Dong, Xianjun, Ernst, Jason, Furey, Terrence S., Gerstein, Mark, Giardine, Belinda, Greven, Melissa, Hardison, Ross C., Harris, Robert S., Herrero, Javier, Hoffman, Michael M., Iyer, Sowmya, Kellis, Manolis, Kheradpour, Pouya, Lassmann, Timo, Li, Qunhua, Lin, Xinying, Marinov, Georgi K., Merkel, Angelika, Mortazavi, Ali, Parker, Stephen C. J., Reddy, Timothy E., Rozowsky, Joel, Schlesinger, Felix, Thurman, Robert E., Wang, Jie, Ward, Lucas D., Whitfield, Troy W., Wilder, Steven P., Wu, Weisheng, Xi, Hualin S., Yip, Kevin Y., Zhuang, Jiali, Bernstein, Bradley E., Green, Eric D., Gunter, Chris, Snyder, Michael, Pazin, Michael J., Lowdon, Rebecca F., Dillon, Laura A. L., Adams, Leslie B., Kelly, Caroline J., Zhang, Julia, Wexler, Judith R., Good, Peter J., Feingold, Elise A., Crawford, Gregory E., Dekker, Job, Elnitski, Laura, Farnham, Peggy J., Giddings, Morgan C., Gingeras, Thomas R., Guigo, Roderic, Hubbard, Timothy J., Kent, W. James, Lieb, Jason D., Margulies, Elliott H., Myers, Richard M., Stamatoyannopoulos, John A., Tenenbaum, Scott A., Weng, Zhiping, White, Kevin P., Wold, Barbara, Yu, Yanbao, Wrobel, John, Risk, Brian A., Gunawardena, Harsha P., Kuiper, Heather C., Maier, Christopher W., Xie, Ling, Chen, Xian, Mikkelsen, Tarjei S., Gillespie, Shawn, Goren, Alon, Ram, Oren, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Eaton, Matthew L., Dobin, Alex, Tanzer, Andrea, Lagarde, Julien, Lin, Wei, Xue, Chenghai, Williams, Brian A., Zaleski, Chris, Roder, Maik, Kokocinski, Felix, Abdelhamid, Rehab F., Alioto, Tyler, Antoshechkin, Igor, Baer, Michael T., Batut, Philippe, Bell, Ian, Bell, Kimberly, Chakrabortty, Sudipto, Chrast, Jacqueline, Curado, Joao, Derrien, Thomas, Drenkow, Jorg, Dumais, Erica, Dumais, Jackie, Duttagupta, Radha, Fastuca, Megan, Fejes-Toth, Kata, Ferreira, Pedro, Foissac, Sylvain, Fullwood, Melissa J., Gao, Hui, Gonzalez, David, Gordon, Assaf, Howald, Cedric, Jha, Sonali, Johnson, Rory, Kapranov, Philipp, King, Brandon, Kingswood, Colin, Li, Guoliang, Luo, Oscar J., Park, Eddie, Preall, Jonathan B., Presaud, Kimberly, Ribeca, Paolo, Robyr, Daniel, Ruan, Xiaoan, Sammeth, Michael, Sandhu, Kuljeet Singh, Schaeffer, Lorain, See, Lei-Hoon, Shahab, Atif, Skancke, Jorgen, Suzuki, Ana Maria, Takahashi, Hazuki, Tilgner, Hagen, Trout, Diane, Walters, Nathalie, Wang, Huaien, Hayashizaki, Yoshihide, Reymond, Alexandre, Antonarakis, Stylianos E., Hannon, Gregory J., Ruan, Yijun, Carninci, Piero, Sloan, Cricket A., Learned, Katrina, Malladi, Venkat S., Wong, Matthew C., Barber, Galt P., Cline, Melissa S., Dreszer, Timothy R., Heitner, Steven G., Karolchik, Donna, Kirkup, Vanessa M., Meyer, Laurence R., Long, Jeffrey C., Maddren, Morgan, Raney, Brian J., Grasfeder, Linda L., Giresi, Paul G., Battenhouse, Anna, Sheffield, Nathan C., Showers, Kimberly A., London, Darin, Bhinge, Akshay A., Shestak, Christopher, Schaner, Matthew R., Ki Kim, Seul, Zhang, Zhuzhu Z., Mieczkowski, Piotr A., Mieczkowska, Joanna O., Liu, Zheng, McDaniell, Ryan M., Ni, Yunyun, Rashid, Naim U., Kim, Min Jae, Adar, Sheera, Zhang, Zhancheng, Wang, Tianyuan, Winter, Deborah, Keefe, Damian, Iyer, Vishwanath R., Zheng, Meizhen, Wang, Ping, Gertz, Jason, Vielmetter, Jost, Partridge, E., Varley, Katherine E., Gasper, Clarke, Bansal, Anita, Pepke, Shirley, Jain, Preti, Amrhein, Henry, Bowling, Kevin M., Anaya, Michael, Cross, Marie K., Muratet, Michael A., Newberry, Kimberly M., McCue, Kenneth, Nesmith, Amy S., Fisher-Aylor, Katherine I., Pusey, Barbara, DeSalvo, Gilberto, Parker, Stephanie L., Balasubramanian, Sreeram, Davis, Nicholas S., Meadows, Sarah K., Eggleston, Tracy, Newberry, J. Scott, Levy, Shawn E., Absher, Devin M., Wong, Wing H., Blow, Matthew J., Visel, Axel, Pennachio, Len A., Petrykowska, Hanna M., Abyzov, Alexej, Aken, Bronwen, Barrell, Daniel, Barson, Gemma, Berry, Andrew, Bignell, Alexandra, Boychenko, Veronika, Bussotti, Giovanni, Davidson, Claire, Despacio-Reyes, Gloria, Diekhans, Mark, Ezkurdia, Iakes, Frankish, Adam, Gilbert, James, Gonzalez, Jose Manuel, Griffiths, Ed, Harte, Rachel, Hendrix, David A., Hunt, Toby, Jungreis, Irwin, Kay, Mike, Khurana, Ekta, Leng, Jing, Lin, Michael F., Loveland, Jane, Lu, Zhi, Manthravadi, Deepa, Mariotti, Marco, Mudge, Jonathan, Mukherjee, Gaurab, Notredame, Cedric, Pei, Baikang, Rodriguez, Jose Manuel, Saunders, Gary, Sboner, Andrea, Searle, Stephen, Sisu, Cristina, Snow, Catherine, Steward, Charlie, Tapanari, Electra, Tress, Michael L., van Baren, Marijke J., Washietl, Stefan, Wilming, Laurens, Zadissa, Amonida, Zhang, Zhengdong, Brent, Michael, Haussler, David, Valencia, Alfonso, Addleman, Nick, Alexander, Roger P., Auerbach, Raymond K., Balasubramanian, Suganthi, Bettinger, Keith, Bhardwaj, Nitin, Boyle, Alan P., Cao, Alina R., Cayting, Philip, Charos, Alexandra, Cheng, Yong, Eastman, Catharine, Euskirchen, Ghia, Fleming, Joseph D., Grubert, Fabian, Habegger, Lukas, Hariharan, Manoj, Harmanci, Arif, Iyengar, Sushma, Jin, Victor X., Karczewski, Konrad J., Kasowski, Maya, Lacroute, Phil, Lam, Hugo, Lamarre-Vincent, Nathan, Lian, Jin, Lindahl-Allen, Marianne, Min, Renqiang, Miotto, Benoit, Monahan, Hannah, Moqtaderi, Zarmik, Mu, Xinmeng J., Ouyang, Zhengqing, Patacsil, Dorrelyn, Raha, Debasish, Ramirez, Lucia, Reed, Brian, Shi, Minyi, Slifer, Teri, Witt, Heather, Wu, Linfeng, Xu, Xiaoqin, Yan, Koon-Kiu, Yang, Xinqiong, Struhl, Kevin, Weissman, Sherman M., Penalva, Luiz O., Karmakar, Subhradip, Bhanvadia, Raj R., Choudhury, Alina, Domanus, Marc, Ma, Lijia, Moran, Jennifer, Victorsen, Alec, Auer, Thomas, Centanin, Lazaro, Eichenlaub, Michael, Gruhl, Franziska, Heermann, Stephan, Hoeckendorf, Burkhard, Inoue, Daigo, Kellner, Tanja, Kirchmaier, Stephan, Mueller, Claudia, Reinhardt, Robert, Schertel, Lea, Schneider, Stephanie, Sinn, Rebecca, Wittbrodt, Beate, Wittbrodt, Jochen, Partridge, E. Christopher, Jain, Gaurav, Balasundaram, Gayathri, Bates, Daniel L., Byron, Rachel, Canfield, Theresa K., Diegel, Morgan J., Dunn, Douglas, Ebersol, Abigail K., Frum, Tristan, Garg, Kavita, Gist, Erica, Hansen, R. Scott, Boatman, Lisa, Haugen, Eric, Humbert, Richard, Johnson, Audra K., Johnson, Ericka M., Kutyavin, Tattyana V., Lee, Kristen, Lotakis, Dimitra, Maurano, Matthew T., Neph, Shane J., Neri, Fiedencio V., Nguyen, Eric D., Qu, Hongzhu, Reynolds, Alex P., Roach, Vaughn, Rynes, Eric, Sanchez, Minerva E., Sandstrom, Richard S., Shafer, Anthony O., Stergachis, Andrew B., Thomas, Sean, Vernot, Benjamin, Vierstra, Jeff, Vong, Shinny, Weaver, Molly A., Yan, Yongqi, Zhang, Miaohua, Akey, Joshua M., Bender, Michael, Dorschner, Michael O., Groudine, Mark, MacCoss, Michael J., Navas, Patrick, Stamatoyannopoulos, George, Beal, Kathryn, Brazma, Alvis, Flicek, Paul, Johnson, Nathan, Lukk, Margus, Luscombe, Nicholas M., Sobral, Daniel, Vaquerizas, Juan M., Batzoglou, Serafim, Sidow, Arend, Hussami, Nadine, Kyriazopoulou-Panagiotopoulou, Sofia, Libbrecht, Max W., Schaub, Marc A., Miller, Webb, Bickel, Peter J., Banfai, Balazs, Boley, Nathan P., Huang, Haiyan, Li, Jingyi Jessica, Noble, William Stafford, Bilmes, Jeffrey A., Buske, Orion J., Sahu, Avinash D., Kharchenko, Peter V., Park, Peter J., Baker, Dannon, Taylor, James, and Lochovsky, Lucas

Subjects
Genetic research, Human genome -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research., Author(s): The ENCODE Project Consortium; Overall coordination (data analysis coordination); Ian Dunham [2]; Anshul Kundaje [3, 82]; Data production leads (data production); Shelley F. Aldred [4]; Patrick J. Collins [4]; [...]

Published
2012
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28. Comparative analysis of the transcriptome across distant species

Author

Gerstein, Mark B., Rozowsky, Joel, Yan, Koon-Kiu, Wang, Daifeng, Cheng, Chao, Brown, James B., Davis, Carrie A., Hillier, LaDeana, Sisu, Cristina, Li, Jingyi Jessica, Pei, Baikang, Harmanci, Arif O., Duff, Michael O., Djebali, Sarah, Alexander, Roger P., Alver, Burak H., Auerbach, Raymond, Bell, Kimberly, Bickel, Peter J., Boeck, Max E., Boley, Nathan P., Booth, Benjamin W., Cherbas, Lucy, Cherbas, Peter, Di, Chao, Dobin, Alex, Drenkow, Jorg, Ewing, Brent, Fang, Gang, Fastuca, Megan, Feingold, Elise A., Frankish, Adam, Gao, Guanjun, Good, Peter J., Guigó, Roderic, Hammonds, Ann, Harrow, Jen, Hoskins, Roger A., Howald, Cédric, Hu, Long, Huang, Haiyan, Hubbard, Tim J. P., Huynh, Chau, Jha, Sonali, Kasper, Dionna, Kato, Masaomi, Kaufman, Thomas C., Kitchen, Robert R., Ladewig, Erik, Lagarde, Julien, Lai, Eric, Leng, Jing, Lu, Zhi, MacCoss, Michael, May, Gemma, McWhirter, Rebecca, Merrihew, Gennifer, Miller, David M., Mortazavi, Ali, Murad, Rabi, Oliver, Brian, Olson, Sara, Park, Peter J., Pazin, Michael J., Perrimon, Norbert, Pervouchine, Dmitri, Reinke, Valerie, Reymond, Alexandre, Robinson, Garrett, Samsonova, Anastasia, Saunders, Gary I., Schlesinger, Felix, Sethi, Anurag, Slack, Frank J., Spencer, William C., Stoiber, Marcus H., Strasbourger, Pnina, Tanzer, Andrea, Thompson, Owen A., Wan, Kenneth H., Wang, Guilin, Wang, Huaien, Watkins, Kathie L., Wen, Jiayu, Wen, Kejia, Xue, Chenghai, Yang, Li, Yip, Kevin, Zaleski, Chris, Zhang, Yan, Zheng, Henry, Brenner, Steven E., Graveley, Brenton R., Celniker, Susan E., Gingeras, Thomas R., and Waterston, Robert

Published
2014
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29. Diversity and dynamics of the Drosophila transcriptome

Author

Brown, James B., Boley, Nathan, Eisman, Robert, May, Gemma E., Stoiber, Marcus H., Duff, Michael O., Booth, Ben W., Wen, Jiayu, Park, Soo, Suzuki, Ana Maria, Wan, Kenneth H., Yu, Charles, Zhang, Dayu, Carlson, Joseph W., Cherbas, Lucy, Eads, Brian D., Miller, David, Mockaitis, Keithanne, Roberts, Johnny, Davis, Carrie A., Frise, Erwin, Hammonds, Ann S., Olson, Sara, Shenker, Sol, Sturgill, David, Samsonova, Anastasia A., Weiszmann, Richard, Robinson, Garret, Hernandez, Juan, Andrews, Justen, Bickel, Peter J., Carninci, Piero, Cherbas, Peter, Gingeras, Thomas R., Hoskins, Roger A., Kaufman, Thomas C., Lai, Eric C., Oliver, Brian, Perrimon, Norbert, Graveley, Brenton R., and Celniker, Susan E.

Published
2014
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30. Machine-Learning Functional Zonation Approach for Characterizing Terrestrial–Aquatic Interfaces: Application to Lake Erie.

Author

Enguehard, Léa, Falco, Nicola, Schmutz, Myriam, Newcomer, Michelle E., Ladau, Joshua, Brown, James B., Bourgeau-Chavez, Laura, and Wainwright, Haruko M.

Subjects
WETLAND soils, COASTAL wetlands, MACHINE learning, BIOGEOCHEMICAL cycles, PLANT productivity, LAKES
Abstract

Ecosystems at coastal terrestrial–aquatic interfaces play a significant role in global biogeochemical cycles. In this study, we aimed to characterize coastal wetlands with particular focus on the co-variability between plant dynamics, topography, soil, and other environmental factors. We proposed a functional zonation approach based on machine learning clustering to identify the spatial regions, i.e., zones that capture these co-varied properties. This approach was applied to publicly available datasets along Lake Erie, in the Great Lakes Region. We investigated the heterogeneity of coastal ecosystem structures as a function of along-shore distance and transverse distance, based on the spatial data layers, including topography, wetland vegetation cover, and the time series of Landsat's enhanced vegetation index (EVI) between 1990 and 2020. Results showed that the topographic metrics (elevation and slope), soil texture, and plant productivity influence the spatial distribution of wetland land-covers (emergent and phragmites). These results highlight a natural organization along the transverse axis, where the elevation and the EVI increase further away from the coastline. In addition, the clustering analysis allowed us to identify regions with distinct environmental characteristics, as well as the ones that are more sensitive to interannual lake-level variations. [ABSTRACT FROM AUTHOR]

Published
2022
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32. *-DCC: A platform to collect, annotate, and explore a large variety of sequencing experiments

Author

Hörtenhuber, Matthias, Mukarram, Abdul K, Stoiber, Marcus H, Brown, James B, and Daub, Carsten O

Subjects
sequencing experiments, databases, sequencing data annotation, Research, AcademicSubjects/SCI02254, sample annotation, AcademicSubjects/SCI00960, Molecular Sequence Annotation, Generic health relevance, Sequence Analysis, Software
Abstract

Background Over the past few years the variety of experimental designs and protocols for sequencing experiments increased greatly. To ensure the wide usability of the produced data beyond an individual project, rich and systematic annotation of the underlying experiments is crucial. Findings We first developed an annotation structure that captures the overall experimental design as well as the relevant details of the steps from the biological sample to the library preparation, the sequencing procedure, and the sequencing and processed files. Through various design features, such as controlled vocabularies and different field requirements, we ensured a high annotation quality, comparability, and ease of annotation. The structure can be easily adapted to a large variety of species. We then implemented the annotation strategy in a user-hosted web platform with data import, query, and export functionality. Conclusions We present here an annotation structure and user-hosted platform for sequencing experiment data, suitable for lab-internal documentation, collaborations, and large-scale annotation efforts.

Published
2020

33. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Author

Birney, Ewan, Stamatoyannopoulos, John A., Dutta, Anindya, Guigo, Roderic, Gingeras, Thomas R., Margulies, Elliott H., Weng, Zhiping, Snyder, Michael, Dermitzakis, Emmanouil T., Thurman, Robert E., Kuehn, Michael S., Taylor, Christopher M., Neph, Shane, Koch, Christoph M., Asthana, Saurabh, Malhotra, Ankit, Adzhubei, Ivan, Greenbaum, Jason A., Andrews, Robert M., Flicek, Paul, Boyle, Patrick J., Cao, Hua, Carter, Nigel P., Clelland, Gayle K., Davis, Sean, Day, Nathan, Dhami, Pawandeep, Dillon, Shane C., Dorschner, Michael O., Fiegler, Heike, Giresi, Paul G., Goldy, Jeff, Hawrylycz, Michael, Haydock, Andrew, Humbert, Richard, James, Keith D., Johnson, Brett E., Johnson, Ericka M., Frum, Tristan T., Rosenzweig, Elizabeth R., Karnani, Neerja, Lee, Kirsten, Lefebvre, Gregory C., Navas, Patrick A., Neri, Fidencio, Parker, Stephen C. J., Sabo, Peter J., Sandstrom, Richard, Shafer, Anthony, Vetrie, David, Weaver, Molly, Wilcox, Sarah, Yu1, Man, Collins, Francis S., Dekker, Job, Lieb, Jason D., Tullius, Thomas D., Crawford, Gregory E., Sunyaev, Shamil, Noble, William S., Dunham, Ian, Denoeud, France, Reymond, Alexandre, Kapranov, Philipp, Rozowsky, Joel, Zheng, Deyou, Castelo, Robert, Frankish, Adam, Harrow, Jennifer, Ghosh, Srinka, Sandelin, Albin, Hofacker, Ivo L., Baertsch, Robert, Keefe, Damian, Dike, Sujit, Cheng, Jill, Hirsch, Heather A., Sekinger, Edward A., Lagarde, Julien, Abril, Josep F., Shahab, Atif, Flamm, Christoph, Fried, Claudia, Hackermuller, Jorg, Hertel, Jana, Lindemeyer, Manja, Missal, Kristin, Tanzer, Andrea, Washietl, Stefan, Korbel, Jan, Emanuelsson, Olof, Pedersen, Jakob S., Holroyd, Nancy, Taylor, Ruth, Swarbreck, David, Matthews, Nicholas, Dickson, Mark C., Thomas, Daryl J., Weirauch, Matthew T., Gilbert, James, Drenkow, Jorg, Bell, Ian, Zhao, XiaoDong, Srinivasan, K.G., Sung, Wing-Kin, Ooi, Hong Sain, Chiu, Kuo Ping, Foissac, Sylvain, Alioto, Tyler, Brent, Michael, Pachter, Lior, Tress, Michael L., Valencia, Alfonso, Choo, Siew Woh, Choo, Chiou Yu, Ucla, Catherine, Manzano, Caroline, Wyss, Carine, Cheung, Evelyn, Clark, Taane G., Brown, James B., Ganesh, Madhavan, Patel, Sandeep, Tammana, Hari, Chrast, Jacqueline, Henrichsen, Charlotte N., Kai, Chikatoshi, Kawai, Jun, Nagalakshmi, Ugrappa, Wu, Jiaqian, Lian, Zheng, Lian, Jin, Newburger, Peter, Zhang, Xueqing, Bickel, Peter, Mattick, John S., Carninci, Piero, Hayashizaki, Yoshihide, Weissman, Sherman, Hubbard, Tim, Myers, Richard M., Rogers, Jane, Stadler, Peter F., Lowe, Todd M., Wei, Chia-Lin, Ruan, Yijun, Struhl, Kevin, Gerstein, Mark, Antonarakis, Stylianos E., Fu, Yutao, Green, Eric D., Karaoz, Ulaş, Siepel, Adam, Taylor, James, Liefer, Laura A., Wetterstrand, Kris A., Good, Peter J., Feingold, Elise A., Guyer, Mark S., Cooper, Gregory M., Asimenos, George, Dewey, Colin N., Hou, Minmei, Nikolaev, Sergey, Montoya-Burgos, Juan I., Loytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Huang, Haiyan, Zhang, Nancy R., Holmes, Ian, Mullikin, James C., Ureta-Vidal, Abel, Paten, Benedict, Seringhaus, Michael, Church, Deanna, Rosenbloom, Kate, Kent, W. James, Stone, Eric A., Batzoglou, Serafim, Goldman, Nick, Hardison, Ross C., Haussler, David, Miller, Webb, Sidow, Arend, Trinklein, Nathan D., Zhang, Zhengdong D., Barrera, Leah, Stuart, Rhona, King, David C., Ameur, Adam, Enroth, Stefan, Bieda, Mark C., Kim, Jonghwan, Bhinge, Akshay A., Jiang, Nan, Liu, Jun, Yao, Fei, Vega, Vinsensius B., Lee, Charlie W.H., Ng, Patrick, Yang, Annie, Moqtaderi, Zarmik, Zhu, Zhou, Xu, Xiaoqin, Squazzo, Sharon, Oberley, Matthew J., Inman, David, Singer, Michael A., Richmond, Todd A., Munn, Kyle J., Rada-Iglesias, Alvaro, Wallerman, Ola, Komorowski, Jan, Fowler, Joanna C., Couttet, Phillippe, Bruce, Alexander W., Dovey, Oliver M., Ellis, Peter D., Langford, Cordelia F., Nix, David A., Euskirchen, Ghia, Hartman, Stephen, Urban, Alexander E., Kraus, Peter, Van Calcar, Sara, Heintzman, Nate, Hoon Kim, Tae, Wang, Kun, Qu, Chunxu, Hon, Gary, Luna, Rosa, Glass, Christopher K., Rosenfeld, M. Geoff, Aldred, Shelley Force, Cooper, Sara J., Halees, Anason, Lin, Jane M., Shulha, Hennady P., Zhang, Xiaoling, Xu, Mousheng, Haidar, Jaafar N. S., Yu, Yong, Birney*, Ewan, Iyer, Vishwanath R., Green, Roland D., Wadelius, Claes, Farnham, Peggy J., Ren, Bing, Harte, Rachel A., Hinrichs, Angie S., Trumbower, Heather, Clawson, Hiram, Hillman-Jackson, Jennifer, Zweig, Ann S., Smith, Kayla, Thakkapallayil, Archana, Barber, Galt, Kuhn, Robert M., Karolchik, Donna, Armengol, Lluis, Bird, Christine P., de Bakker, Paul I. W., Kern, Andrew D., Lopez-Bigas, Nuria, Martin, Joel D., Stranger, Barbara E., Woodroffe, Abigail, Davydov, Eugene, Dimas, Antigone, Eyras, Eduardo, Hallgrimsdottir, Ingileif B., Huppert, Julian, Zody, Michael C., Abecasis, Goncalo R., Estivill, Xavier, Bouffard, Gerard G., Guan, Xiaobin, Hansen, Nancy F., Idol, Jacquelyn R., Maduro, Valerie V.B., Maskeri, Baishali, McDowell, Jennifer C., Park, Morgan, Thomas, Pamela J., Young, Alice C., Blakesley, Robert W., Baylor College of Medicine, Human Genome Sequencing Center, Muzny, Donna M., Sodergren, Erica, Wheeler, David A., Worley, Kim C., Jiang, Huaiyang, Weinstock, George M., Gibbs, Richard A., Graves, Tina, Fulton, Robert, Mardis, Elaine R., Wilson, Richard K., Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B., Chang, Jean L., Lindblad-Toh, Kerstin, Lander, Eric S., Koriabine, Maxim, Nefedov, Mikhail, Osoegawa, Kazutoyo, Yoshinaga, Yuko, Zhu, Baoli, and de Jong, Pieter J.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): The ENCODE Project Consortium; Analysis Coordination; Ewan Birney (corresponding author) [1]; John A. Stamatoyannopoulos (corresponding author) [2]; Anindya Dutta (corresponding author) [3]; Roderic Guigó (corresponding author) [4, 5]; Thomas [...]

Published
2007
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34. Downscaled hyper-resolution (400 m) gridded datasets of daily precipitation and temperature (2008-2019) for East Taylor subbasin (western United States).

Author

Mital, Utkarsh, Dwivedi, Dipankar, Brown, James B., and Steefel, Carl I.

Subjects
WATER security, SPATIAL resolution, TEMPERATURE, DOWNSCALING (Climatology)
Abstract

High resolution gridded datasets of meteorological variables are needed in order to resolve fine-scale hydrological gradients in complex mountainous terrain. Across the United States, the highest available spatial resolution of gridded datasets of daily meteorological records is approximately 800 m. This work presents gridded datasets of daily precipitation and mean temperature for the East-Taylor subbasin (in western United States) covering a 12-year period (2008-2019) at a high spatial resolution (400 m). The datasets are generated using a downscaling framework that uses data-driven models to learn relationships between climate variables and topography. We observe that downscaled datasets of precipitation and mean temperature exhibit smoother spatial gradients compared to their coarser counterparts. Additionally, we also observe that when downscaled datasets are reaggregated to the original resolution (800 m), the mean residual error is almost zero, ensuring spatial consistency with the original data. Furthermore, the downscaled datasets are observed to be linearly related to elevation, which is consistent with the methodology underlying the original 800 m product. Finally, we validate the spatial patterns exhibited by downscaled datasets via an example use case that models lidar-derived estimates of snowpack. The presented dataset constitutes a valuable resource to resolve fine-sale hydrological gradients in the mountainous terrain of the East-Taylor subbasin, which is an important study area in the context of water security for southwestern United States and Mexico. The dataset is publicly available at https://doi.org/10.15485/1822259 (Mital et al., 2021). [ABSTRACT FROM AUTHOR]

Published
2022
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36. The developmental transcriptome of Drosophila melanogaster

Author

Graveley, Brenton R., Brooks, Angela N., Carlson, Joseph W., Duff, Michael O., Landolin, Jane M., Yang, Li, Artieri, Carlo G., van Baren, Marijke J., Boley, Nathan, Booth, Benjamin W., Brown, James B., Cherbas, Lucy, Davis, Carrie A., Dobin, Alex, Li, Renhua, Lin, Wei, Malone, John H., Mattiuzzo, Nicolas R., Miller, David, Sturgill, David, Tuch, Brian B., Zaleski, Chris, Zhang, Dayu, Blanchette, Marco, Dudoit, Sandrine, Eads, Brian, Green, Richard E., Hammonds, Ann, Jiang, Lichun, Kapranov, Phil, Langton, Laura, Perrimon, Norbert, Sandler, Jeremy E., Wan, Kenneth H., Willingham, Aarron, Zhang, Yu, Zou, Yi, Andrews, Justen, Bickel, Peter J., Brenner, Steven E., Brent, Michael R., Cherbas, Peter, Gingeras, Thomas R., Hoskins, Roger A., Kaufman, Thomas C., Oliver, Brian, and Celniker, Susan E.

Published
2011
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42. Investigation of the phenomena of frictionless transport at low temperatures

Author

Brown, James B.

Subjects
536
Abstract

The work reported in this thesis divides naturally into two parts. The first concerns the development of a technique for isolating the supra-surface film of Helium II from the bulk liquid and the Tap our pressure over it, and the study of properties of the film in equilibrium with the gas phase only. The second part of the thesis gives the results of a general investigation of high transport rates in the film. A solution of the problem of isolating the film was seen to depend upon the devising of a practical form of super-fluid filter. Capillary leaks through metal tubes containing closely packed wires, such as those used by Allen and Misener (J. F. Allen and A. D. Misener, Nature, 141, 75, 1938) in their work on the viscosity of the bulk liquid were found to be suitable. The construction and testing of such wire-tube filters is described. The performance data are tabulated for a typical one, consisting in this case of two tubes in parallel, each containing 900 wires of #47 Eureka in a 5 cm. long cupronickel tube, initially .157" outside diameter, .072" inside diameter, drawn down finally to .104" outside diameter. Representative values of the amounts of gas, N.T.P., passed by this filter into a vacuum from one atmosphere of helium were: .01 cc./min. at 290°K; .06 cc./min. at 90°K; .45 cc./min. at 20°K; 7 cc./min. at 4.3°K. As the pressure is reduced in the helium temperature region, the amount of gas passed diminishes correspondingly, and at 4 cm. Hg., 2.2°K, it becomes .07 cc./min. N.T.P. Below the λ-point, the filters pass no measureable quantity of gas when they are not dipping into liquid. The total transport circumference provided by the above combination of two leaks in parallel is 30 cm., giving a maximum possible film flow corresponding to 110 cc. gas/min., N.T.P. It is pointed cut that the filters can be easily incorporated into metal apparatus, and an example is given of their application to the study of the vapour pressure over the film, and also the effect on the transport rate of lowering the vapour pressure over the film. It is found that the vapour pressure in equilibrium with the isolated film is the same as that of the bulk liquid at the same temperature. Above a critical rate of pumping, apparently determined by the incidental film flow up an auxiliary tube, and the evaporation loss of the particular arrangement used, the pressure over the isolated film suddenly decreases, and transport stops. It is shown that at the same time there is a sudden fall of temperature at the transport surface, and apparently a thermomechanical effect in the film which prevents it from moving into the container being pumped. It seems possible that the film is still present but immobilized, and if this is the case, oppositely directed thermomechanical forces along the path do not cancel each other, but act independently. A variety of geometrical arrangements hare been investigated for the occurrence of high transfer rates. It has been found that the transport through a small hole in a surface can be several times larger than that calculated from the perimeter of the hole and the rate established by Daunt and Mendelssohn (J. G. Daunt and K. Mendelssohn, Proc. Roy. Soc. A, 170, 423, 1939) for flow over cylindrical beakers. A number of such holes hare been tested, and it has been found that there is sometimes a strong dependence of the transport rate on the height of the hole above the upper liquid level, and on the shape of the inside surface of the beaker. Experiments have been made similar to those of K. R. Atkins (Nature, 161, 925, 1948), who reported high transfer rates in capillaries ending in bulbs, and under the influence of the temperature gradients. The results of Atkins have not been verified, and a probable explanation, based upon the interpretation of his geometrical arrangement, has been given for the apparently high rates observed in the second of his experiments. Some possible explanations for the other discrepancies are considered, and it is recognized that hitherto unexplored experimental factors may be involved. Experiments have been made to eliminate certain possibilities, one in particular being the formation of thick films under certain conditions. This has led incidentally to an observation of a striking example of the high conductivity of helium as a free liquid, apart from the presence of solids on which subsurface could be carried. A summary of the experimental background of the field investigated, and some of the theoretical interpretations, is given in two chapters at the beginning of the thesis.

Published
1948

43. Detention operations, behavior modification and counter insurgency

Author

Brown, James B., Goepner, Erik W., and Clark, James M.

Subjects
Counterinsurgency, Detention of persons, Insurgency, Behavior modification, General interest, Military and naval science
Abstract

[ILLUSTRATION OMITTED] INFLUENCING THE POPULATION is critical in a counterinsurgency, and the detainee population in Iraq represents a particularly salient demographic in that endeavor. Can an Iraqi detainee's extremist behavior [...]

Published
2009

44. BLOCCS: Block Sparse Canonical Correlation Analysis With Application To Interpretable Omics Integration

Author

Solari, Omid Shams, Safavi, Rojin, and Brown, James B.

Subjects
FOS: Computer and information sciences, Computer Science - Machine Learning, Statistics - Machine Learning, Machine Learning (stat.ML), Machine Learning (cs.LG)
Abstract

We introduce Block Sparse Canonical Correlation Analysis which estimates multiple pairs of canonical directions (together a "block") at once, resulting in significantly improved orthogonality of the sparse directions which, we demonstrate, translates to more interpretable solutions. Our approach builds on the sparse CCA method of (Solari, Brown, and Bickel 2019) in that we also express the bi-convex objective of our block formulation as a concave minimization problem over an orthogonal k-frame in a unit Euclidean ball, which in turn, due to concavity of the objective, is shrunk to a Stiefel manifold, which is optimized via gradient descent algorithm. Our simulations show that our method outperforms existing sCCA algorithms and implementations in terms of computational cost and stability, mainly due to the drastic shrinkage of our search space, and the correlation within and orthogonality between pairs of estimated canonical covariates. Finally, we apply our method, available as an R-package called BLOCCS, to multi-omic data on Lung Squamous Cell Carcinoma(LUSC) obtained via The Cancer Genome Atlas, and demonstrate its capability in capturing meaningful biological associations relevant to the hypothesis under study rather than spurious dominant variations., 8 pages

Published
2019

45. Radiological events in the homeland

Author

Brown, James B., Coble, Russell E., and Chase, Emery J.

Subjects
National security -- Evaluation -- Equipment and supplies, Nuclear weapons -- Usage -- Equipment and supplies -- Evaluation, Terrorism -- Equipment and supplies, Military and naval science, Al-Qaeda -- Equipment and supplies
Abstract

The leadership of al Qaeda has issued fatwas justifying the use of nuclear weapons to bring destruction to the American homeland, and its campaign to recruit those who have expertise [...]

Published
2008

47. Civil disturbance lessons learned from Kopsovo

Author

Brown, James B.

Subjects
Military and naval science
Abstract

When the 793d Military Police Battalion moved into Kosovo, literally at the head of the first formations of Kosovo Force (KFOR) soldiers from the 1st Infantry Division (known as the [...]

Published
2003

50. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author

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, I T, Lee, Wen-Jane, Leong, Aaron, Liao, Jiemin, Liu, Chunyu, Liu, Yongmei, Lindgren, Cecilia M, Linneberg, Allan, Malerba, Giovanni, Mamakou, Vasiliki, Marouli, Eirini, Maruthur, Nisa M, Matchan, Angela, McKean-Cowdin, Roberta, McLeod, Olga, Metcalf, Ginger A, Mohlke, Karen L, Muzny, Donna M, Ntalla, Ioanna, Palmer, Nicholette D, Pasko, Dorota, Peter, Andreas, Rayner, Nigel W, Renström, Frida, Rice, Ken, Sala, Cinzia F, Sennblad, Bengt, Serafetinidis, Ioannis, Smith, Jennifer A, Soranzo, Nicole, Speliotes, Elizabeth K, Stahl, Eli A, Stirrups, Kathleen, Tentolouris, Nikos, Thanopoulou, Anastasia, Torres, Mina, Traglia, Michela, Tsafantakis, Emmanouil, Javad, Sundas, Yanek, Lisa R, Zengini, Eleni, Becker, Diane M, Bis, Joshua C, Brown, James B, Adrienne Cupples, L, Hansen, Torben, Ingelsson, Erik, Karter, Andrew J, Lorenzo, Carlos, Mathias, Rasika A, Norris, Jill M, Peloso, Gina M, Sheu, Wayne H.-H., Toniolo, Daniela, Vaidya, Dhananjay, Varma, Rohit, Wagenknecht, Lynne E, Boeing, Heiner, Bottinger, Erwin P, Dedoussis, George, Deloukas, Panos, Ferrannini, Ele, Franco, Oscar H, Franks, Paul W, Gibbs, Richard A, Gudnason, Vilmundur, Hamsten, Anders, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, Hofman, Albert, Jansson, Jan-Håkan, Langenberg, Claudia, Launer, Lenore J, Levy, Daniel, Oostra, Ben A, O’Donnell, Christopher J, O’Rahilly, Stephen, Padmanabhan, Sandosh, Pankow, James S, Polasek, Ozren, Province, Michael A, Rich, Stephen S, Ridker, Paul M, Rudan, Igor, Schulze, Matthias B, Smith, Blair H, Uitterlinden, André G, Walker, Mark, Watkins, Hugh, Wong, Tien Y, Zeggini, Eleftheria, Sharp, Stephen J, Forouhi, Nita G, Kerrison, Nicola D, Lucarelli, Debora ME, Sims, Matt, Barroso, Inês, McCarthy, Mark I, Arriola, Larraitz, Balkau, Beverley, Barricarte, Aurelio, Gonzalez, Carlos, Grioni, Sara, Kaaks, Rudolf, Key, Timothy J, Navarro, Carmen, Nilsson, Peter M, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, J. Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Sánchez, María–José, Slimani, Nadia, Tjonneland, Anne, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Riboli, Elio, Laakso, Markku, Borecki, Ingrid B, Chasman, Daniel I, Pedersen, Oluf, Psaty, Bruce M, Shyong Tai, E, van Duijn, Cornelia M, Wareham, Nicholas J, Waterworth, Dawn M, Boerwinkle, Eric, Linda Kao, W H, Florez, Jose C, Loos, Ruth J.F., Wilson, James G, Frayling, Timothy M, Siscovick, David S, Dupuis, Josée, Rotter, Jerome I, Meigs, James B, Scott, Robert A, Goodarzi, Mark O, Jennifer Wessel, Audrey Y. Chu, Sara M. Willems, Shuai Wang, Hanieh Yaghootkar, Jennifer A. Brody, Marco Dauriz, Marie France Hivert, Sridharan Raghavan, Leonard Lipovich, Bertha Hidalgo, Keolu Fox, Jennifer E. Huffman, Ping An, Yingchang Lu, Laura J. Rasmussen Torvik, Niels Grarup, Margaret G. Ehm, Li Li, Abigail S. Baldridge, Alena Stančáková, Ravinder Abrol, Céline Besse, Anne Boland, Jette Bork Jensen, Myriam Fornage, Daniel F. Freitag, Melissa E. Garcia, Xiuqing Guo, Kazuo Hara, Aaron Isaacs, Johanna Jakobsdottir, Leslie A. Lange, Jill C. Layton, Man Li, Jing Hua Zhao, Karina Meidtner, Alanna C. Morrison, Mike A. Nalls, Marjolein J. Peter, Maria Sabater Lleal, Claudia Schurmann, Angela Silveira, Albert V. Smith, Lorraine Southam, Marcus H. Stoiber, Rona J. Strawbridge, Kent D. Taylor, Tibor V. Varga, Kristine H. Allin, Najaf Amin, Jennifer L. Aponte, Tin, Aung, Barbieri, CATERINA MARIA, Nathan A. Bihlmeyer, Michael Boehnke, Cristina Bombieri, Donald W. Bowden, Sean M. Burns, Yuning Chen, Yii DerI Chen, Ching Yu Cheng, Adolfo Correa, Jacek Czajkowski, Abbas Dehghan, Georg B. Ehret, Gudny Eiriksdottir, Stefan A. Escher, Aliki Eleni Farmaki, Mattias Frånberg, Giovanni Gambaro, Franco Giulianini, William A. Goddard, Anuj Goel, Omri Gottesman, Megan L. Grove, Stefan Gustafsson, Yang Hai, Göran Hallmans, Jiyoung Heo, Per Hoffmann, Mohammad K. Ikram, Richard A. Jensen, Marit E. Jørgensen, Torben Jørgensen, Maria Karaleftheri, Chiea C. Khor, Andrea Kirkpatrick, Aldi T. Kraja, Johanna Kuusisto, Ethan M. Lange, I. T. Lee, Wen Jane Lee, Aaron Leong, Jiemin Liao, Chunyu Liu, Yongmei Liu, Cecilia M. Lindgren, Allan Linneberg, Giovanni Malerba, Vasiliki Mamakou, Eirini Marouli, Nisa M. Maruthur, Angela Matchan, Roberta McKean Cowdin, Olga McLeod, Ginger A. Metcalf, Karen L. Mohlke, Donna M. Muzny, Ioanna Ntalla, Nicholette D. Palmer, Dorota Pasko, Andreas Peter, Nigel W. Rayner, Frida Renström, Ken Rice, Cinzia F. Sala, Bengt Sennblad, Ioannis Serafetinidis, Jennifer A. Smith, Nicole Soranzo, Elizabeth K. Speliote, Eli A. Stahl, Kathleen Stirrup, Nikos Tentolouris, Anastasia Thanopoulou, Mina Torres, Michela Traglia, Emmanouil Tsafantakis, Sundas Javad, Lisa R. Yanek, Eleni Zengini, Diane M. Becker, Joshua C. Bi, James B. Brown, L. Adrienne Cupple, Torben Hansen, Erik Ingelsson, Andrew J. Karter, Carlos Lorenzo, Rasika A. Mathias, Jill M. Norri, Gina M. Peloso, Wayne H. H. Sheu, Daniela Toniolo, Dhananjay Vaidya, Rohit Varma, Lynne E. Wagenknecht, Heiner Boeing, Erwin P. Bottinger, George Dedoussis, Panos Delouka, Ele Ferrannini, Oscar H. Franco, Paul W. Franks, Richard A. Gibb, Vilmundur Gudnason, Anders Hamsten, Tamara B. Harris, Andrew T. Hattersley, Caroline Hayward, Albert Hofman, Jan Håkan Jansson, Claudia Langenberg, Lenore J. Launer, Daniel Levy, Ben A. Oostra, Christopher J. O’Donnell, Stephen O’Rahilly, Sandosh Padmanabhan, James S. Pankow, Ozren Polasek, Michael A. Province, Stephen S. Rich, Paul M. Ridker, Igor Rudan, Matthias B. Schulze, Blair H. Smith, André G. Uitterlinden, Mark Walker, Hugh Watkins, Tien Y. Wong, Eleftheria Zeggini, The EPIC InterAct Consortium, Markku Laakso, Ingrid B. Borecki, Daniel I. Chasman, Oluf Pedersen, Bruce M. Psaty, E. Shyong Tai, Cornelia M. van Duijn, Nicholas J. Wareham, Dawn M. Waterworth, Eric Boerwinkle, W. H. Linda Kao, Jose C. Florez, Ruth J. F. Loos, James G. Wilson, Timothy M. Frayling, David S. Siscovick, Josée Dupuis, Jerome I. Rotter, James B. Meigs, Robert A. Scott, Mark O., Goodarzi, 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, Niel, 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, Abba, Ehret, Georg B, Eiriksdottir, Gudny, Escher, Stefan A, Farmaki, Aliki Eleni, Frånberg, Mattia, 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, I. T, Lee, Wen Jane, Leong, Aaron, Liao, Jiemin, Liu, Chunyu, Liu, Yongmei, Lindgren, Cecilia M, Linneberg, Allan, Malerba, Giovanni, Mamakou, Vasiliki, Marouli, Eirini, Maruthur, Nisa M, Matchan, Angela, McKean Cowdin, Roberta, Mcleod, Olga, Metcalf, Ginger A, Mohlke, Karen L, Muzny, Donna M, Ntalla, Ioanna, Palmer, Nicholette D, Pasko, Dorota, Peter, Andrea, Rayner, Nigel W, Renström, Frida, Rice, Ken, Sala, Cinzia F, Sennblad, Bengt, Serafetinidis, Ioanni, Smith, Jennifer A, Soranzo, Nicole, Speliotes, Elizabeth K, Stahl, Eli A, Stirrups, Kathleen, Tentolouris, Niko, Thanopoulou, Anastasia, Torres, Mina, Traglia, Michela, Tsafantakis, Emmanouil, Javad, Sunda, Yanek, Lisa R, Zengini, Eleni, Becker, Diane M, Bis, Joshua C, Brown, James B, Cupples, L. Adrienne, Hansen, Torben, Ingelsson, Erik, Karter, Andrew J, Lorenzo, Carlo, Mathias, Rasika A, Norris, Jill M, Peloso, Gina M, Sheu, Wayne H. H, Toniolo, Daniela, Vaidya, Dhananjay, Varma, Rohit, Wagenknecht, Lynne E, Boeing, Heiner, Bottinger, Erwin P, Dedoussis, George, Deloukas, Pano, Ferrannini, Ele, Franco, Oscar H, Franks, Paul W, Gibbs, Richard A, Gudnason, Vilmundur, Hamsten, Ander, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, Hofman, Albert, Jansson, Jan Håkan, Langenberg, Claudia, Launer, Lenore J, Levy, Daniel, Oostra, Ben A, O'Donnell, Christopher J, O'Rahilly, Stephen, Padmanabhan, Sandosh, Pankow, James S, Polasek, Ozren, Province, Michael A, Rich, Stephen S, Ridker, Paul M, Rudan, Igor, Schulze, Matthias B, Smith, Blair H, Uitterlinden, André G, Walker, Mark, Watkins, Hugh, Wong, Tien Y, Zeggini, Eleftheria, Laakso, Markku, Borecki, Ingrid B, Chasman, Daniel I, Pedersen, Oluf, Psaty, Bruce M, Tai, E. Shyong, van Duijn, Cornelia M, Wareham, Nicholas J, Waterworth, Dawn M, Boerwinkle, Eric, Kao, W. H. Linda, Florez, Jose C, Loos, Ruth J. F, Wilson, James G, Frayling, Timothy M, Siscovick, David S, Dupuis, Josée, Rotter, Jerome I, Meigs, James B, Scott, Robert A, Goodarzi, Mark O., Panico, Salvatore, Soranzo, Nicole [0000-0003-1095-3852], Johnson, Kathleen [0000-0002-6823-3252], Langenberg, Claudia [0000-0002-5017-7344], O'Rahilly, Stephen [0000-0003-2199-4449], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Epidemiology, Surgery, Internal Medicine, Radiology & Nuclear Medicine, Clinical Genetics, Obstetrics & Gynecology, and Cell biology

Subjects
Blood Glucose, diabetes, exome chip, SEQUENCING DATA, European Continental Ancestry Group, Black People, Genetic Association Studie, Endocrinology and Diabetes, TRIGLYCERIDE LEVELS, Polymorphism, Single Nucleotide, Article, White People, Glucagon-Like Peptide-1 Receptor, Cohort Studies, SDG 3 - Good Health and Well-being, Mutation Rate, GLYCEMIC TRAITS, Humans, Settore MED/14 - NEFROLOGIA, Insulin, Exome, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Genetic Association Studies, African Continental Ancestry Group, Oligonucleotide Array Sequence Analysis, PLASMA-GLUCOSE, INSULIN-RESISTANCE, epidemiology/genetics, Science & Technology, GLUCAGON-LIKE PEPTIDE-1, Diabetes, Genetic Variation, GERMLINE MUTATIONS, Fasting, epidemiology/genetics, Cohort Studies, Exome, diabetes, Multidisciplinary Sciences, RECEPTOR GENE, Diabetes Mellitus, Type 2, Genetic Loci, Endokrinologi och diabetes, CODING VARIATION, Glucose-6-Phosphatase, Science & Technology - Other Topics, exome chip, Human
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., Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1R significantly associated with these traits.

Published
2015

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