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3. Cryptocurrencies and Zero Mode Wave guides: An unclouded path to a more contiguous Cannabis sativa L. genome assembly

Author

McKernan, Kevin, Helbert, Yvonne, Kane, Liam, Ebling, Heather, Zhang, Lei, Liu, Biao, Eaton, Zachary, Sun, Luo, Dimalanta, Eileen, Kingan, Sarah, Baybayan, Primo, Press, Maximilian, Barbazuk, William, and Harkins, Timothy

Subjects
Cryptocurrency, Medicinal Genomics, Phase Genomics, NEB, Pacific Biosciences, DASH, Genomics, Cannabis
Abstract

We describe the use of a Decentralized Autonomous Organization (DAO) to crypto-fund the single molecule sequencing and publication of a Type II Cannabis plant. This resulted in the construction of the most contiguous Cannabis genome assembly to date. The combined use of the Dash cryptocurrency, DAOs, and Pacific Biosciences sequencing delivered a 1.03 Gb genome with a N50 of 665Kb in 77 days from funding to public upload. This represents a 230 fold improvement in the contiguity of the first cannabis assemblies in 2011 and a 4 fold improvement over all cannabis assemblies to date. 34Gb of additional sequencing pushed the assembly to a N50 of 3.8Mb. Hi-C data from Phase Genomics further scaffolded the assembly to 35 contigs at an N50 of 74Mb but requires additional curation. The genome is partially phased and larger than previously reported (2N = 1.33Gb). The CBCA, THCA and CBDA synthase gene clusters have been phased onto respective contigs demonstrating tandem repeat expansions.

Published
2022
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5. Missense mutations in THCAS are associated with Cannabigerolic Acid expression in Cannabis sativa L

Author

McKernan, Kevin, Zhang, Lei, Helbert, Yvonne, Kane, Liam T, and McLaughlin, Stephen

Subjects
S355N, CBDAS, THCAS, Next Generation Sequencing, Cannabigerol, CBG, hemp, Type IV Cannabis, Cannabinoid Synthesis, Cannabis
Abstract

The chemical expression of THCA and CBDA has been previously attributed to copy number gains and losses in THCAS and CBDAS. Here we describe an alternative mechanism to ablate THCAS activity in 5 CBGA dominant cannabis varietals. Five cannabis cultivars from three unique cultivators surprisingly contain a THCAS gene but also share homozygous Pro333Arg and Ser355Asn mutations in THCAS. Pro333Arg is commonly found in THCAS dominant varietals but is uniquely found in a homozygous state in CBGA varietals in conjunction with homozygous Ser355Asn missense mutations. These results hint at convergent evolution in cannabinoid synthesis where selection for and against THCA synthesis has been applied., https://www.kannapedia.net

Published
2022
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9. Addendum - Corman Drosten Review Report by an International Consortium of Scientists in Life Sciences (ICSLS)

Author

Borger, Pieter, Malhotra, Rajesh Kumar, Yeadon, Michael, Clare, Craig, McKernan, Kevin, Steger, Klaus, McSheehy, Paul, Angelova, Lidiya, Franchi, Fabio, Binder, Thomas, Ullrich, Henrik, Ohashi, Makoto, Scoglio, Stefano, Doesburg-van Kleffens, Marjolein, Gilbert, Dorothea, Klement, Rainer J., Schruefer, Ruth, Pieksma, Berber W., Bonte, Jan, Dalle Carbonare, Bruno H., Corbett, Kevin P., and Kämmerer, Ulrike

Subjects
Research on research, SARS-CoV-2, Meta-research, PCR tests, COVID-19, Conflicts of interest
Abstract

Background:: After submitting our review report on Corman et al. (referred hereinafter as CD-report) and republishing it on a scientific preprint server (http://doi.org/10.5281/zenodo.4298004) and Researchgate.net we offered the report for public discussion at cormandrostenreview.com on 27th November 2020. The scientific community provided additional literature, references, and analyses concerning the CD-report and the Corman et al. manuscript. Several “advocatus diaboli” confronted us with correct or assumed problems in our report. The most common critique of the CD-report was the lack of “wet lab” experiments to support our concerns over the technical flaws in the PCR protocol. Aim: This vibrant debate on our CD report has provided additional information worthy of further public documentation to address these critiques. We summarize the current published knowledge of “wet lab testing”, routine diagnostic use and validation of the original PCR-Protocol described by Corman et al. Further, this addendum highlights that independent research groups (some of them with Corman and/or Drosten as author) also pointed out important concerns with the original manuscript and Corman PCR protocol distributed by the WHO. Many of these references were already provided by the authors of the original CD-report but it is worth underscoring their relevance to the formation of our critiques of the CD manuscript. Methods: We searched the literature for ‘SARS-CoV-2 qPCR’ and ‘Corman’ or ‘Charité’. Then we combined these references with those provided by other scientists working in relevant Life Sciences/data analysis fields. In the first section of the addendum, the publications will be discussed point by point, highlighting their findings in relation to the CD-report. In a second section, additional aspects about the Corman et al . publication are discussed. This spans a meta-analysis of the unusual peer-review process, timeframes, and further technical vulnerabilities of the Corman et al . PCR-protocol. An additional concern was raised about the CD-report regarding the discussion of appropriate controls. We cite several studies that underscore the importance of internal controls in assessing viral load and the lack of such internal controls in the Corman qPCR method. These internal controls are required for normalizing swab sampling variance and they are critical for interpreting viral load. They are notably absent from the Corman PCR protocol. Several people also expressed confusion regarding the NCBI submissions provided by Corman et al . The sequences provided lack two of the target gene sequences Corman et al. claim to target. The only sequences referenced in the manuscript are listed ( KC633203, KC633204, KC633201, GU190221, GU190222, GU190223) and none of these have sequences that match their N and E gene primers. This not only brings their validation into question but also prevents others from reproducing the work presented in Corman et al. Results: We present 20 scientific publications providing ‘wet lab’ evidence of the performance of the Corman et al. PCR protocol. Of those, 17 found problems with incorrect primer design (mismatches, dimer formation, melting temperature) in the SARS-CoV-2 specific “confirmatory” test named RdRp-PCR for “RNA-dependent RNA-polymerase” or the E-gene assay. These documented problems include: ● Documented primer dimers and False Positives in non-template controls (NTCs) ● Documented poor sensitivity and False Negatives compared to other assays ● No internal control to normalize the sample preparation variability and its impact on viral load estimation ● No defined Ct for calling samples “Positive cases” ● Poorly documented positive controls and sequences used in their study Conclusions: We believe the references provided in this addendum itemize the scientific consensus evident in the literature regarding the flaws in the original PCR detection method for SARs-CoV-2 published by Corman et al. . Further, since several important flaws were published in peer-reviewed journals, the lack of correction of the original PCR protocol by either Eurosurveillance or as an update in the Charité-WHO protocol brings into question the scientific integrity of the authors of Corman et al. These references settle any remaining debate that the Corman et al. manuscript should be retracted on technical grounds alone. The rapidity of the peer-review and conflicts of interest are even more troubling., This is an addendum to our report also published on Zenodo: 10.5281/zenodo.4298004

Published
2021
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11. External peer review of the RTPCR test to detect SARS-CoV-2 reveals 10 major scientific flaws at the molecular and methodological level: consequences for false positive results

Author

Borger, Pieter, Malhotra, Rajesh Kumar, Yeadon, Michael, Craig, Clare, McKernan, Kevin, Steger, Klaus, McSheehy, Paul, Angelova, Lidiya, Franchi, Fabio, Binder, Thomas, Ullrich, Henrik, Ohashi, Makoto, Scoglio, Stefano, Doesburg-van Kleffens, Marjolein, Gilbert, Dorothea, Klement, Rainer Johannes, Schrüfer, Ruth, Pieksma, Berber W., Bonte, Jan, Dalle Carbonare, Bruno H., Corbett, Kevin P., and Kämmer, Ulrike

Subjects
SARS-CoV-2, COVID-19, qRT-PCR
Abstract

In the publication entitled “Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR” (Eurosurveillance 25(8) 2020) the authors present a diagnostic workflow and RT-qPCR protocol for detection and diagnostics of 2019-nCoV (now known as SARS-CoV-2), which they claim to be validated, as well as being a robust diagnostic methodology for use in public-health laboratory settings. In light of all the consequences resulting from this very publication for societies worldwide, a group of independent researchers performed a point-by-point review of the aforesaid publication in which 1) all components of the presented test design were cross checked, 2) the RT-qPCR protocol-recommendations were assesses w.r.t. good laboratory practice, and 3) parameters examined against relevant scientific literature covering the field. The published RT-qPCR protocol for detection and diagnostics of 2019-nCoV and the manuscript suffer from numerous technical and scientific errors, including insufficient primer design, a problematic and insufficient RT-qPCR protocol, and the absence of an accurate test validation. Neither the presented test nor the manuscript itself fulfils the requirements for an acceptable scientific publication. Further, serious conflicts of interest of the authors are not mentioned. Finally, the very short timescale between submission and acceptance of the publication (24 hours) signifies that a systematic peer review process was either not performed here, or of problematic poor quality. We provide compelling evidence of several scientific inadequacies, errors and flaws. Considering the scientific and methodological blemishes presented here, we are confident that the editorial board of Eurosurveillance has no other choice but to retract the publication., More information on this paper can be found here: https://cormandrostenreview.com/

Published
2020
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12. Evolution of genes and genomes on the Drosophila phylogeny

Author

Clark, Andrew G., Eisen, Michael B., Smith, Douglas R., Bergman, Casey M., Oliver, Brian, Markow, Therese A., Kaufman, Thomas C., Kellis, Manolis, Gelbart, William, Iyer, Venky N., Pollard, Daniel A., Sackton, Timothy B., Larracuente, Amanda M., Singh, Nadia D., Abad, Jose P., Abt, Dawn N., Adryan, Boris, Aguade, Montserrat, Akashi, Hiroshi, Anderson, Wyatt W., Aquadro, Charles F., Ardell, David H., Arguello, Roman, Artieri, Carlo G., Barbash, Daniel A., Barker, Daniel, Barsanti, Paolo, Batterham, Phil, Batzoglou, Serafim, Begun, Dave, Bhutkar, Arjun, Blanco, Enrico, Bosak, Stephanie A., Bradley, Robert K., Brand, Adrianne D., Brent, Michael R., Brooks, Angela N., Brown, Randall H., Butlin, Roger K., Caggese, Corrado, Calvi, Brian R., Bernardo de Carvalho, A., Caspi, Anat, Castrezana, Sergio, Celniker, Susan E., Chang, Jean L., Chapple, Charles, Chatterji, Sourav, Chinwalla, Asif, Civetta, Alberto, Clifton, Sandra W., Comeron, Josep M., Costello, James C., Coyne, Jerry A., Daub, Jennifer, David, Robert G., Delcher, Arthur L., Delehaunty, Kim, Do, Chuong B., Ebling, Heather, Edwards, Kevin, Eickbush, Thomas, Evans, Jay D., Filipski, Alan, Findeiß, Sven, Freyhult, Eva, Fulton, Lucinda, Fulton, Robert, Garcia, Ana C. L., Gardiner, Anastasia, Garfield, David A., Garvin, Barry E., Gibson, Greg, Gilbert, Don, Gnerre, Sante, Godfrey, Jennifer, Good, Robert, Gotea, Valer, Gravely, Brenton, Greenberg, Anthony J., Griffiths-Jones, Sam, Gross, Samuel, Guigo, Roderic, Gustafson, Erik A., Haerty, Wilfried, Hahn, Matthew W., Halligan, Daniel L., Halpern, Aaron L., Halter, Gillian M., Han, Mira V., Heger, Andreas, Hillier, LaDeana, Hinrichs, Angie S., Holmes, Ian, Hoskins, Roger A., Hubisz, Melissa J., Hultmark, Dan, Huntley, Melanie A., Jaffe, David B., Jagadeeshan, Santosh, Jeck, William R., Johnson, Justin, Jones, Corbin D., Jordan, William C., Karpen, Gary H., Kataoka, Eiko, Keightley, Peter D., Kheradpour, Pouya, Kirkness, Ewen F., Koerich, Leonardo B., Kristiansen, Karsten, Kudrna, Dave, Kulathinal, Rob J., Kumar, Sudhir, Kwok, Roberta, Lander, Eric, Langley, Charles H., Lapoint, Richard, Lazzaro, Brian P., Lee, So-Jeong, Levesque, Lisa, Li, Ruiqiang, Lin, Chiao-Feng, Lin, Michael F., Lindblad-Toh, Kerstin, Llopart, Ana, Long, Manyuan, Low, Lloyd, Lozovsky, Elena, Lu, Jian, Luo, Meizhong, Machado, Carlos A., Makalowski, Wojciech, Marzo, Mar, Matsuda, Muneo, Matzkin, Luciano, McAllister, Bryant, McBride, Carolyn S., McKernan, Brendan, McKernan, Kevin, Mendez-Lago, Maria, Minx, Patrick, Mollenhauer, Michael U., Montooth, Kristi, Mount, Stephen M., Mu, Xu, Myers, Eugene, Negre, Barbara, Newfeld, Stuart, Nielsen, Rasmus, Noor, Mohamed A. F., O'Grady, Patrick, Pachter, Lior, Papaceit, Montserrat, Parisi, Matthew J., Parisi, Michael, Parts, Leopold, Pedersen, Jakob S., Pesole, Graziano, Phillippy, Adam M., Ponting, Chris P., Pop, Mihai, Porcelli, Damiano, Powell, Jeffrey R., Prohaska, Sonja, Pruitt, Kim, Puig, Marta, Quesneville, Hadi, Ravi Ram, Kristipati, Rand, David, Rasmussen, Matthew D., Reed, Laura K., Reenan, Robert, Reily, Amy, Remington, Karin A., Rieger, Tania T., Ritchie, Michael G., Robin, Charles, Rogers, Yu-Hui, Rohde, Claudia, Rozas, Julio, Rubenfield, Marc J., Ruiz, Alfredo, Russo, Susan, Salzberg, Steven L., Sanchez-Gracia, Alejandro, Saranga, David J., Sato, Hajime, Schaeffer, Stephen W., Schatz, Michael C., Schlenke, Todd, Schwartz, Russell, Segarra, Carmen, Singh, Rama S., Sirot, Laura, Sirota, Marina, Sisneros, Nicholas B., Smith, Chris D., Smith, Temple F., Spieth, John, Stage, Deborah E., Stark, Alexander, Stephan, Wolfgang, Strausberg, Robert L., Strempel, Sebastian, Sturgill, David, Sutton, Granger, Sutton, Granger G., Tao, Wei, Teichmann, Sarah, Tobari, Yoshiko N., Tomimura, Yoshihiko, Tsolas, Jason M., Valente, Vera L. S., Venter, Eli, Craig Venter, J., Vicario, Saverio, Vieira, Filipe G., Vilella, Albert J., Villasante, Alfredo, Walenz, Brian, Wang, Jun, Wasserman, Marvin, Watts, Thomas, Wilson, Derek, Wilson, Richard K., Wing, Rod A., Wolfner, Mariana F., Wong, Alex, Ka-Shu Wong, Gane, Wu, Chung-I, Wu, Gabriel, Yamamoto, Daisuke, Yang, Hsiao-Pei, Yang, Shiaw-Pyng, Yorke, James A., Yoshida, Kiyohito, Zdobnov, Evgeny, Zhang, Peili, Zhang, Yu, Zimin, Aleksey V., Baldwin, Jennifer, Abdouelleil, Amr, Abdulkadir, Jamal, Abebe, Adal, Abera, Brikti, Abreu, Justin, Christophe Acer, St, Aftuck, Lynne, Alexander, Allen, An, Peter, Anderson, Erica, Anderson, Scott, Arachi, Harindra, Azer, Marc, Bachantsang, Pasang, Barry, Andrew, Bayul, Tashi, Berlin, Aaron, Bessette, Daniel, Bloom, Toby, Blye, Jason, Boguslavskiy, Leonid, Bonnet, Claude, Boukhgalter, Boris, Bourzgui, Imane, Brown, Adam, Cahill, Patrick, Channer, Sheridon, Cheshatsang, Yama, Chuda, Lisa, Citroen, Mieke, Collymore, Alville, Cooke, Patrick, Costello, Maura, D'Aco, Katie, Daza, Riza, De Haan, Georgius, DeGray, Stuart, DeMaso, Christina, Dhargay, Norbu, Dooley, Kimberly, Dooley, Erin, Doricent, Missole, Dorje, Passang, Dorjee, Kunsang, Dupes, Alan, Elong, Richard, Falk, Jill, Farina, Abderrahim, Faro, Susan, Ferguson, Diallo, Fisher, Sheila, Foley, Chelsea D., Franke, Alicia, Friedrich, Dennis, Gadbois, Loryn, Gearin, Gary, Gearin, Christina R., Giannoukos, Georgia, Goode, Tina, Graham, Joseph, Grandbois, Edward, Grewal, Sharleen, Gyaltsen, Kunsang, Hafez, Nabil, Hagos, Birhane, Hall, Jennifer, Henson, Charlotte, Hollinger, Andrew, Honan, Tracey, Huard, Monika D., Hughes, Leanne, Hurhula, Brian, Erii Husby, M, Kamat, Asha, Kanga, Ben, Kashin, Seva, Khazanovich, Dmitry, Kisner, Peter, Lance, Krista, Lara, Marcia, Lee, William, Lennon, Niall, Letendre, Frances, LeVine, Rosie, Lipovsky, Alex, Liu, Xiaohong, Liu, Jinlei, Liu, Shangtao, Lokyitsang, Tashi, Lokyitsang, Yeshi, Lubonja, Rakela, Lui, Annie, MacDonald, Pen, Magnisalis, Vasilia, Maru, Kebede, Matthews, Charles, McCusker, William, McDonough, Susan, Mehta, Teena, Meldrim, James, Meneus, Louis, Mihai, Oana, Mihalev, Atanas, Mihova, Tanya, Mittelman, Rachel, Mlenga, Valentine, Montmayeur, Anna, Mulrain, Leonidas, Navidi, Adam, Naylor, Jerome, Negash, Tamrat, Nguyen, Thu, Nguyen, Nga, Nicol, Robert, Norbu, Choe, Norbu, Nyima, Novod, Nathaniel, O'Neill, Barry, Osman, Sahal, Markiewicz, Eva, Oyono, Otero L., Patti, Christopher, Phunkhang, Pema, Pierre, Fritz, Priest, Margaret, Raghuraman, Sujaa, Rege, Filip, Reyes, Rebecca, Rise, Cecil, Rogov, Peter, Ross, Keenan, Ryan, Elizabeth, Settipalli, Sampath, Shea, Terry, Sherpa, Ngawang, Shi, Lu, Shih, Diana, Sparrow, Todd, Spaulding, Jessica, Stalker, John, Stange-Thomann, Nicole, Stavropoulos, Sharon, Stone, Catherine, Strader, Christopher, Tesfaye, Senait, Thomson, Talene, Thoulutsang, Yama, Thoulutsang, Dawa, Topham, Kerri, Topping, Ira, Tsamla, Tsamla, Vassiliev, Helen, Vo, Andy, Wangchuk, Tsering, Wangdi, Tsering, Weiand, Michael, Wilkinson, Jane, Wilson, Adam, Yadav, Shailendra, Young, Geneva, Yu, Qing, Zembek, Lisa, Zhong, Danni, Zimmer, Andrew, Zwirko, Zac, Alvarez, Pablo, Brockman, Will, Butler, Jonathan, Chin, CheeWhye, Grabherr, Manfred, Kleber, Michael, Mauceli, Evan, and MacCallum, Iain

Abstract

Author(s): Drosophila 12 Genomes Consortium; Project Leaders; Andrew G. Clark (corresponding author) [1]; Michael B. Eisen (corresponding author) [2, 3]; Douglas R. Smith (corresponding author) [4]; Casey M. Bergman (corresponding [...]

Published
2007
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16. Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype

Author

Jaillon, Olivier, Aury, Jean-Marc, Brunet, Frederic, Petit, Jean-Louis, Stange-Thomann, Nicole, Mauceli, Evan, Bouneau, Laurence, Fischer, Cecile, Ozouf-Costaz, Catherine, Bernot, Alain, Nicaud, Sophie, Jaffe, David, Fisher, Sheila, Lutfalla, Georges, Dossat, Carole, Segurens, Beatrice, Dasilva, Corinne, Salanoubat, Marcel, Levy, Michael, Boudet, Nathalie, Castellano, Sergi, Anthouard, Veronique, Jubin, Claire, Castelli, Vanina, Katinka, Michael, Vacherie, Benoit, Biemont, Christian, Skalli, Zineb, Cattolico, Laurence, Poulain, Julie, de Berardinis, Veronique, Cruaud, Corinne, Duprat, Simone, Brottier, Philippe, Coutanceau, Jean-Pierre, Gouzy, Jerome, Parra, Genis, Lardier, Guillaume, Chapple, Charles, McKernan, Kevin J., McEwan, Paul, Bosak, Stephanie, Kellis, Manolis, Volff, Jean-Nicolas, Guigo, Roderic, Zody, Michael C., Mesirov, Jill, Lindblad-Toh, Kerstin, Birren, Bruce, Nusbaum, Chad, Kahn, Daniel, Robinson-Rechavi, Marc, Laudet, Vincent, Schachter, Vincent, Quetier, Francis, Saurin, William, Scarpelli, Claude, Wincker, Patrick, Lander, Eric S., Weissenbach, Jean, and Roest Crollius, Hugues

Abstract

Author(s): Olivier Jaillon [1]; Jean-Marc Aury [1]; Frédéric Brunet [2]; Jean-Louis Petit [1]; Nicole Stange-Thomann [3]; Evan Mauceli [3]; Laurence Bouneau [1]; Cécile Fischer [1]; Catherine Ozouf-Costaz [4]; Alain Bernot [...]

Published
2004
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17. Initial sequencing and analysis of the human genome

Author

Lander, Eric S., Linton, Lauren M., Birren, Bruce, Nusbaum, Chad, Zody, Michael C., Baldwin, Jennifer, Devon, Keri, Dewar, Ken, Doyle, Michael, FitzHugh, William, Funke, Roel, Gage, Diane, Harris, Katrina, Heaford, Andrew, Howland, John, Kann, Lisa, Lehoczky, Jessica, LeVine, Rosie, McEwan, Paul, McKernan, Kevin, Meldrim, James, Mesirov, Jill P., Miranda, Cher, Morris, William, Naylor, Jerome, Raymond, Christina, Rosetti, Mark, Santos, Ralph, Sheridan, Andrew, Sougnez, Carrie, Stange-Thomann, Nicole, Stojanovic, Nikola, Subramanian, Aravind, Wyman, Dudley, Rogers, Jane, Sulston, John, Ainscough, Rachael, Beck, Stephan, Bentley, David, Burton, John, Clee, Christopher, Carter, Nigel, Coulson, Alan, Deadman, Rebecca, Deloukas, Panos, Dunham, Andrew, Dunham, Ian, Durbin, Richard, French, Lisa, Grafham, Darren, Gregory, Simon, Hubbard, Tim, Humphray, Sean, Hunt, Adrienne, Jones, Matthew, Lloyd, Christine, McMurray, Amanda, Matthews, Lucy, Mercer, Simon, Milne, Sarah, Mullikin, James C., Mungall, Andrew, Plumb, Robert, Ross, Mark, Shownkeen, Ratna, Sims, Sarah, Waterston, Robert H., Wilson, Richard K., Hillier, LaDeana W., McPherson, John D., Marra, Marco A., Mardis, Elaine R., Fulton, Lucinda A., Chinwalla, Asif T., Pepin, Kymberlie H., Gish, Warren R., Chissoe, Stephanie L., Wendl, Michael C., Delehaunty, Kim D., Miner, Tracie L., Delehaunty, Andrew, Kramer, Jason B., Cook, Lisa L., Fulton, Robert S., Johnson, Douglas L., Minx, Patrick J., Clifton, Sandra W., Hawkins, Trevor, Branscomb, Elbert, Predki, Paul, Richardson, Paul, Wenning, Sarah, Slezak, Tom, Doggett, Norman, Cheng, Jan-Fang, Olsen, Anne, Lucas, Susan, Elkin, Christopher, Uberbacher, Edward, Frazier, Marvin, Gibbs, Richard A., Muzny, Donna M., Scherer, Steven E., Bouck, John B., Sodergren, Erica J., Worley, Kim C., Rives, Catherine M., Gorrell, James H., Metzker, Michael L., Naylor, Susan L., Kucherlapati, Raju S., Nelson, David L., Weinstock, George M., Sakaki, Yoshiyuki, Fujiyama, Asao, Hattori, Masahira, Yada, Tetsushi, Toyoda, Atsushi, Itoh, Takehiko, Kawagoe, Chiharu, Watanabe, Hidemi, Totoki, Yasushi, Taylor, Todd, Weissenbach, Jean, Heilig, Roland, Saurin, William, Artiguenave, Francois, Brottier, Philippe, Bruls, Thomas, Pelletier, Eric, Robert, Catherine, Wincker, Patrick, Rosenthal, Andre, Platzer, Matthias, Nyakatura, Gerald, Taudien, Stefan, Rump, Andreas, Smith, Douglas R., Doucette-Stamm, Lynn, Rubenfield, Marc, Weinstock, Keith, Lee, Hong Mei, Dubois, JoAnn, Yang, Huanming, Yu, Jun, Wang, Jian, Huang, Guyang, Gu, Jun, Hood, Leroy, Rowen, Lee, Madan, Anup, Qin, Shizen, Davis, Ronald W., Federspiel, Nancy A., Abola, A. Pia, Proctor, Michael J., Roe, Bruce A., Chen, Feng, Pan, Huaqin, Ramser, Juliane, Lehrach, Hans, Reinhardt, Richard, McCombie, W. Richard, de la Bastide, Melissa, Dedhia, Neilay, Blocker, Helmut, Hornischer, Klaus, Nordsiek, Gabriele, Agarwala, Richa, Aravind, L., Bailey, Jeffrey A., Bateman, Alex, Batzoglou, Serafim, Birney, Ewan, Bork, Peer, Brown, Daniel G., Burge, Christopher B., Cerutti, Lorenzo, Chen, Hsiu-Chuan, Church, Deanna, Clamp, Michele, Copley, Richard R., Doerks, Tobias, Eddy, Sean R., Eichler, Evan E., Furey, Terrence S., Galagan, James, Gilbert, James G. R., Harmon, Cyrus, Hayashizaki, Yoshihide, Haussler, David, Hermjakob, Henning, Hokamp, Karsten, Jang, Wonhee, Johnson, L. Steven, Jones, Thomas A., Kasif, Simon, Kaspryzk, Arek, Kennedy, Scot, Kent, W. James, Kitts, Paul, Koonin, Eugene V., Korf, Ian, Kulp, David, Lancet, Doron, Lowe, Todd M., McLysaght, Aoife, Mikkelsen, Tarjei, Moran, John V., Mulder, Nicola, Pollara, Victor J., Ponting, Chris P., Schuler, Greg, Schultz, Jorg, Slater, Guy, Smit, Arian F. A., Stupka, Elia, Szustakowki, Joseph, Thierry-Mieg, Danielle, Thierry-Mieg, Jean, Wagner, Lukas, Wallis, John, Wheeler, Raymond, Williams, Alan, Wolf, Yuri I., Wolfe, Kenneth H., Yang, Shiaw-Pyng, Yeh, Ru-Fang, Collins, Francis, Guyer, Mark S., Peterson, Jane, Felsenfeld, Adam, Wetterstrand, Kris A., Myers, Richard M., Schmutz, Jeremy, Dickson, Mark, Grimwood, Jane, Cox, David R., Olson, Maynard V., Kaul, Rajinder, Raymond, Christopher, Shimizu, Nobuyoshi, Kawasaki, Kazuhiko, Minoshima, Shinsei, Evans, Glen A., Athanasiou, Maria, Schultz, Roger, Patrinos, Aristides, and Morgan, Michael J.

Abstract

Author(s): International Human Genome Sequencing Consortium; Whitehead Institute for Biomedical Research, Center for Genome Research:; Eric S. Lander [1]; Lauren M. Linton [1]; Bruce Birren [1]; Chad Nusbaum [1]; Michael [...]

Published
2001
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18. An integrated semiconductor device enabling non-optical genome sequencing

Author

Rothberg, Jonathan M., Hinz, Wolfgang, Rearick, Todd M., Schultz, Jonathan, Mileski, William, Davey, Mel, Leamon, John H., Johnson, Kim, Milgrew, Mark J., Edwards, Matthew, Hoon, Jeremy, Simons, Jan F., Marran, David, Myers, Jason W., Davidson, John F., Branting, Annika, Nobile, John R., Puc, Bernard P., Light, David, Clark, Travis A., Huber, Martin, Branciforte, Jeffrey T., Stoner, Isaac B., Cawley, Simon E., Lyons, Michael, Fu, Yutao, Homer, Nils, Sedova, Marina, Miao, Xin, Reed, Brian, Sabina, Jeffrey, Feierstein, Erika, Schorn, Michelle, Alanjary, Mohammad, Dimalanta, Eileen, Dressman, Devin, Kasinskas, Rachel, Sokolsky, Tanya, Fidanza, Jacqueline A., Namsaraev, Eugeni, McKernan, Kevin J., and Williams, Alan

Published
2011
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19. A map of human genome variation from population-scale sequencing

Author

Durbin, Richard M., Altshuler, David L., Durbin, Richard M., Abecasis, Gonçalo R., Bentley, David R., Chakravarti, Aravinda, Clark, Andrew G., Collins, Francis S., De La Vega, Francisco M., Donnelly, Peter, Egholm, Michael, Flicek, Paul, Gabriel, Stacey B., Gibbs, Richard A., Knoppers, Bartha M., Lander, Eric S., Lehrach, Hans, Mardis, Elaine R., McVean, Gil A., Nickerson, Debbie A., Peltonen, Leena, Schafer, Alan J., Sherry, Stephen T., Wang, Jun, Wilson, Richard K., Gibbs, Richard A., Deiros, David, Metzker, Mike, Muzny, Donna, Reid, Jeff, Wheeler, David, Wang, Jun, Li, Jingxiang, Jian, Min, Li, Guoqing, Li, Ruiqiang, Liang, Huiqing, Tian, Geng, Wang, Bo, Wang, Jian, Wang, Wei, Yang, Huanming, Zhang, Xiuqing, Zheng, Huisong, Lander, Eric S., Altshuler, David L., Ambrogio, Lauren, Bloom, Toby, Cibulskis, Kristian, Fennell, Tim J., Gabriel, Stacey B., Jaffe, David B., Shefler, Erica, Sougnez, Carrie L., Bentley, David R., Gormley, Niall, Humphray, Sean, Kingsbury, Zoya, Koko-Gonzales, Paula, Stone, Jennifer, McKernan, Kevin J., Costa, Gina L., Ichikawa, Jeffry K., Lee, Clarence C., Sudbrak, Ralf, Lehrach, Hans, Borodina, Tatiana A., Dahl, Andreas, Davydov, Alexey N., Marquardt, Peter, Mertes, Florian, Nietfeld, Wilfiried, Rosenstiel, Philip, Schreiber, Stefan, Soldatov, Aleksey V., Timmermann, Bernd, Tolzmann, Marius, Egholm, Michael, Affourtit, Jason, Ashworth, Dana, Attiya, Said, Bachorski, Melissa, Buglione, Eli, Burke, Adam, Caprio, Amanda, Celone, Christopher, Clark, Shauna, Conners, David, Desany, Brian, Gu, Lisa, Guccione, Lorri, Kao, Kalvin, Kebbel, Andrew, Knowlton, Jennifer, Labrecque, Matthew, McDade, Louise, Mealmaker, Craig, Minderman, Melissa, Nawrocki, Anne, Niazi, Faheem, Pareja, Kristen, Ramenani, Ravi, Riches, David, Song, Wanmin, Turcotte, Cynthia, Wang, Shally, Mardis, Elaine R., Wilson, Richard K., Dooling, David, Fulton, Lucinda, Fulton, Robert, Weinstock, George, Durbin, Richard M., Burton, John, Carter, David M., Churcher, Carol, Coffey, Alison, Cox, Anthony, Palotie, Aarno, Quail, Michael, Skelly, Tom, Stalker, James, Swerdlow, Harold P., Turner, Daniel, De Witte, Anniek, Giles, Shane, Bainbridge, Matthew, Challis, Danny, Sabo, Aniko, Yu, Fuli, Yu, Jin, Fang, Xiaodong, Guo, Xiaosen, Li, Yingrui, Luo, Ruibang, Tai, Shuaishuai, Wu, Honglong, Zheng, Hancheng, Zheng, Xiaole, Zhou, Yan, Marth, Gabor T., Garrison, Erik P., Huang, Weichun, Indap, Amit, Kural, Deniz, Lee, Wan-Ping, Fung Leong, Wen, Quinlan, Aaron R., Stewart, Chip, Stromberg, Michael P., Ward, Alistair N., Wu, Jiantao, Lee, Charles, Mills, Ryan E., Shi, Xinghua, Daly, Mark J., DePristo, Mark A., Ball, Aaron D., Banks, Eric, Browning, Brian L., Garimella, Kiran V., Grossman, Sharon R., Handsaker, Robert E., Hanna, Matt, Hartl, Chris, Kernytsky, Andrew M., Korn, Joshua M., Li, Heng, Maguire, Jared R., McCarroll, Steven A., McKenna, Aaron, Nemesh, James C., Philippakis, Anthony A., Poplin, Ryan E., Price, Alkes, Rivas, Manuel A., Sabeti, Pardis C., Schaffner, Stephen F., Shlyakhter, Ilya A., Cooper, David N., Ball, Edward V., Mort, Matthew, Phillips, Andrew D., Stenson, Peter D., Sebat, Jonathan, Makarov, Vladimir, Ye, Kenny, Yoon, Seungtai C., Bustamante, Carlos D., Clark, Andrew G., Boyko, Adam, Degenhardt, Jeremiah, Gravel, Simon, Gutenkunst, Ryan N., Kaganovich, Mark, Keinan, Alon, Lacroute, Phil, Ma, Xin, Reynolds, Andy, Clarke, Laura, Flicek, Paul, Cunningham, Fiona, Herrero, Javier, Keenen, Stephen, Kulesha, Eugene, Leinonen, Rasko, McLaren, William M., Radhakrishnan, Rajesh, Smith, Richard E., Zalunin, Vadim, Zheng-Bradley, Xiangqun, Korbel, Jan O., Stütz, Adrian M., Humphray, Sean, Bauer, Markus, Cheetham, Keira R., Cox, Tony, Eberle, Michael, James, Terena, Kahn, Scott, Murray, Lisa, Ye, Kai, De La Vega, Francisco M., Fu, Yutao, Hyland, Fiona C. L., Manning, Jonathan M., McLaughlin, Stephen F., Peckham, Heather E., Sakarya, Onur, Sun, Yongming A., Tsung, Eric F., Batzer, Mark A., Konkel, Miriam K., Walker, Jerilyn A., Albrecht, Marcus W., Amstislavskiy, Vyacheslav S., Herwig, Ralf, Parkhomchuk, Dimitri V., Sherry, Stephen T., Agarwala, Richa, Khouri, Hoda M., Morgulis, Aleksandr O., Paschall, Justin E., Phan, Lon D., Rotmistrovsky, Kirill E., Sanders, Robert D., Shumway, Martin F., Xiao, Chunlin, McVean, Gil A., Auton, Adam, Iqbal, Zamin, Lunter, Gerton, Marchini, Jonathan L., Moutsianas, Loukas, Myers, Simon, Tumian, Afidalina, Desany, Brian, Knight, James, Winer, Roger, Craig, David W., Beckstrom-Sternberg, Steve M., Christoforides, Alexis, Kurdoglu, Ahmet A., Pearson, John V., Sinari, Shripad A., Tembe, Waibhav D., Haussler, David, Hinrichs, Angie S., Katzman, Sol J., Kern, Andrew, Kuhn, Robert M., Przeworski, Molly, Hernandez, Ryan D., Howie, Bryan, Kelley, Joanna L., Cord Melton, S., Abecasis, Gonçalo R., Li, Yun, Anderson, Paul, Blackwell, Tom, Chen, Wei, Cookson, William O., Ding, Jun, Min Kang, Hyun, Lathrop, Mark, Liang, Liming, Moffatt, Miriam F., Scheet, Paul, Sidore, Carlo, Snyder, Matthew, Zhan, Xiaowei, Zöllner, Sebastian, Awadalla, Philip, Casals, Ferran, Idaghdour, Youssef, Keebler, John, Stone, Eric A., Zilversmit, Martine, Jorde, Lynn, Xing, Jinchuan, Eichler, Evan E., Aksay, Gozde, Alkan, Can, Hajirasouliha, Iman, Hormozdiari, Fereydoun, Sahinalp, Cenk S., Sudmant, Peter H., Mardis, Elaine R., Chen, Ken, Chinwalla, Asif, Ding, Li, Koboldt, Daniel C., McLellan, Mike D., Wallis, John W., Wendl, Michael C., Zhang, Qunyuan, Albers, Cornelis A., Ayub, Qasim, Balasubramaniam, Senduran, Barrett, Jeffrey C., Chen, Yuan, Conrad, Donald F., Danecek, Petr, Dermitzakis, Emmanouil T., Hu, Min, Huang, Ni, Hurles, Matt E., Jin, Hanjun, Jostins, Luke, Keane, Thomas M., Quang Le, Si, Lindsay, Sarah, Long, Quan, MacArthur, Daniel G., Montgomery, Stephen B., Parts, Leopold, Tyler-Smith, Chris, Walter, Klaudia, Zhang, Yujun, Gerstein, Mark B., Snyder, Michael, Abyzov, Alexej, Balasubramanian, Suganthi, Bjornson, Robert, Du, Jiang, Grubert, Fabian, Habegger, Lukas, Haraksingh, Rajini, Jee, Justin, Khurana, Ekta, Lam, Hugo Y. K., Leng, Jing, Jasmine Mu, Xinmeng, Urban, Alexander E., Zhang, Zhengdong, Lee, Charles, McCarroll, Steven A., DePristo, Mark A., Korbel, Jan O., De La Vega, Francisco M., Blackwell, Tom, Eichler, Evan E., Kidd, Jeffrey M., Hurles, Matt E., Gibbs, Richard A., Coafra, Cristian, Dinh, Huyen, Kovar, Christie, Lee, Sandy, Nazareth, Lynne, Marth, Gabor T., Wilkinson, Jane, Flicek, Paul, Sherry, Stephen T., Abecasis, Gonçalo R., Mardis, Elaine R., Coffey, Allison, Scott, Carol, Gerstein, Mark B., Chakravarti, Aravinda, Knoppers, Bartha M., Bustamante, Carlos D., Gharani, Neda, Jorde, Lynn, Kaye, Jane S., Kent, Alastair, Li, Taosha, McGuire, Amy L., Ossorio, Pilar N., Rotimi, Charles N., Su, Yeyang, Toji, Lorraine H., Brooks, Lisa D., Felsenfeld, Adam L., McEwen, Jean E., Abdallah, Assya, Juenger, Christopher R., Clemm, Nicholas C., Duncanson, Audrey, Green, Eric D., Guyer, Mark S., and Peterson, Jane L.

Published
2010
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20. A small-cell lung cancer genome with complex signatures of tobacco exposure

Author

Pleasance, Erin D., Stephens, Philip J., OʼMeara, Sarah, McBride, David J., Meynert, Alison, Jones, David, Lin, Meng-Lay, Beare, David, Lau, King Wai, Greenman, Chris, Varela, Ignacio, Nik-Zainal, Serena, Davies, Helen R., Ordoñez, Gonzalo R., Mudie, Laura J., Latimer, Calli, Edkins, Sarah, Stebbings, Lucy, Chen, Lina, Jia, Mingming, Leroy, Catherine, Marshall, John, Menzies, Andrew, Butler, Adam, Teague, Jon W., Mangion, Jonathon, Sun, Yongming A., McLaughlin, Stephen F., Peckham, Heather E., Tsung, Eric F., Costa, Gina L., Lee, Clarence C., Minna, John D., Gazdar, Adi, Birney, Ewan, Rhodes, Michael D., McKernan, Kevin J., Stratton, Michael R., Futreal, Andrew P., and Campbell, Peter J.

Published
2010
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21. Mapping and sequencing of structural variation from eight human genomes

Author

Kidd, Jeffrey M., Cooper, Gregory M., Donahue, William F., Hayden, Hillary S., Sampas, Nick, Graves, Tina, Hansen, Nancy, Teague, Brian, Alkan, Can, Antonacci, Francesca, Haugen, Eric, Zerr, Troy, Yamada, N. Alice, Tsang, Peter, Newman, Tera L., Tüzün, Eray, Cheng, Ze, Ebling, Heather M., Tusneem, Nadeem, David, Robert, Gillett, Will, Phelps, Karen A., Weaver, Molly, Saranga, David, Brand, Adrianne, Tao, Wei, Gustafson, Erik, McKernan, Kevin, Chen, Lin, Malig, Maika, Smith, Joshua D., Korn, Joshua M., McCarroll, Steven A., Altshuler, David A., Peiffer, Daniel A., Dorschner, Michael, Stamatoyannopoulos, John, Schwartz, David, Nickerson, Deborah A., Mullikin, James C., Wilson, Richard K., Bruhn, Laurakay, Olson, Maynard V., Kaul, Rajinder, Smith, Douglas R., and Eichler, Evan E.

Published
2008
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24. A small cell lung cancer genome reports complex tobacco exposure signatures

Author

Pleasance, Erin D, Stephens, Philip J, O'Meara, Sarah, McBride, David J, Meynert, Alison, Jones, David, Lin, Meng-Lay, Beare, David, Lau, King Wai, Greenman, Chris, Varela, Ignacio, Nik-Zainal, Serena, Davies, Helen R, Ordoñez, Gonzalo R, Mudie, Laura J, Latimer, Calli, Edkins, Sarah, Stebbings, Lucy, Chen, Lina, Jia, Mingming, Leroy, Catherine, Marshall, John, Menzies, Andrew, Butler, Adam, Teague, Jon W, Mangion, Jonathon, Sun, Yongming A, McLaughlin, Stephen F, Peckham, Heather E, Tsung, Eric F, Costa, Gina L, Lee, Clarence C, Minna, John D, Gazdar, Adi, Birney, Ewan, Rhodes, Michael D, McKernan, Kevin J, Stratton, Michael R, Futreal, P Andrew, and Campbell, Peter J

Subjects
Lung Neoplasms, DNA Copy Number Variations, DNA Repair, Genome, Human, DNA Mutational Analysis, Smoking, DNA Helicases, Exons, Small Cell Lung Carcinoma, Article, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Mutagenesis, Insertional, Cell Line, Tumor, Mutation, Tobacco, Carcinogens, Humans, Promoter Regions, Genetic, DNA Damage, Sequence Deletion
Abstract

Cancer is driven by mutation. Worldwide, tobacco smoking is the principal lifestyle exposure that causes cancer, exerting carcinogenicity through60 chemicals that bind and mutate DNA. Using massively parallel sequencing technology, we sequenced a small-cell lung cancer cell line, NCI-H209, to explore the mutational burden associated with tobacco smoking. A total of 22,910 somatic substitutions were identified, including 134 in coding exons. Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context. Effects of transcription-coupled repair and a second, more general, expression-linked repair pathway were evident. We identified a tandem duplication that duplicates exons 3-8 of CHD7 in frame, and another two lines carrying PVT1-CHD7 fusion genes, indicating that CHD7 may be recurrently rearranged in this disease. These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes, cellular repair pathways and gene networks associated with cancer.

Published
2009

26. Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding

Author

McKernan, Kevin Judd, Peckham, Heather E, Costa, Gina L., McLaughlin, Stephen F., Yutao Fu, Tsung, Eric F., Clouser, Christopher R., Duncan, Cisyla, Ichikawa, Jeffrey K., Lee, Clarence C., Zheng Zhang, Ranade, Swati S., Dimalanta, Eileen T., Hyland, Fiona C., Sokolsky, Tanya D., Lei Zhang, Sheridan, Andrew, Haoning Fu, Hendrickson, Cynthia L., Bin Li, Kotler, Lev, Stuart, Jeremy R., Malek, Joel A., Manning, Jonathan M., Antipova, Alena A., Perez, Damon S., Moore, Michael P., Hayashibara, Kathleen C., Lyons, Michael R., Beaudoin, Robert E., Coleman, Brittany E., Laptewicz, Michael W., Sannicandro, Adam E, Rhodes, Michael D., Gottimukkala, Rajesh K., Shan Yang, Bafna, Vineet, Bashir, Ali, MacBride, Andrew, Alkan, Can, Kidd, Jeffrey M., Eichler, Evan E., Reese, Martin G., De La Vega, Francisco M., and Blanchard, Alan P.

Subjects
Nucleotide sequence -- Analysis, Haplotypes -- Analysis, Human genome -- Research, Single nucleotide polymorphisms -- Research, Health
Published
2009

27. Rapid whole-genome mutational profiling using next-generation sequencing technologies

Author

Smith, Douglas R., Quinlan, Aaron R., Peckham, Heather E., Marth, Gabor T., Jeffries, Thomas W., McKernan, Kevin J., Rokhsar, Daniel S., Makowsky, Kathryn, Wei Tao, Woolf, Betty, Lei Shen, Donahue, William F., Tusneem, Nadeem, Stromberg, Michael P., Stewart, Donald A., Lu Zhang, Feng Chen, Hillman, David, Chapman, Jarrod, Blanchard, Alan P., Ranade, Swati S., Warner, Jason B., Lee, Clarence C., Coleman, Brittney E., Zheng Zhang, McLaughlin, Stephen F., Malek, Joel A., and Sorenson, Jon M.

Subjects
Gene mutations -- Research, Nucleotide sequencing -- Usage, Genomes -- Research, Health
Abstract

The article demonstrates the application of various new, high-throughput, next-generation parallel sequencing technologies in conducting the rapid whole-genome mutational profiling of various organisms. The new technologies are shown to be extremely rapid and cost-effective in detecting mutations in various evolved and engineered organisms.

Published
2008

28. Metagenomic analysis of medicinal Cannabis samples; pathogenic bacteria, toxigenic fungi, and beneficial microbes grow in culture-based yeast and mold tests

Author

McKernan, Kevin, primary, Spangler, Jessica, additional, Helbert, Yvonne, additional, Lynch, Ryan C., additional, Devitt-Lee, Adrian, additional, Zhang, Lei, additional, Orphe, Wendell, additional, Warner, Jason, additional, Foss, Theodore, additional, Hudalla, Christopher J., additional, Silva, Matthew, additional, and Smith, Douglas R., additional

Published
2016
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30. The genome of M. acetivorans reveals extensive metabolic and physiological diversity

Author

Galagan, James E., Naylor, Jerome; Stange-Thomann, Nicole; DeArellano, Kurt; Johnson, Robin; Linton, Lauren;, Barber, Robert D.; Cann, Isaac; Graham, David E.; Grahame, David A.; Guss, Adam M.; Hedderich, Reiner; Ingram-Smith, Cheryl; Kuettner, H. Craig; Krzycki, Joseph A.; Leigh, John A.; Weixi Li, Liu, Jinfeng; Mukhopadhyay, Biswarup; Reeve, John N.; Smith, Kerry; Springer, Timothy A.; Umayam, Lowell A.; White, Owen; White, Robert H.; Macario, Everly Conway de; Ferry, James G., Jarrell, Ken F.; Jing, Hua; Macario, Alberto J.L.; Paulsen, Ian; Pritchett, Matthew; Sowers, Kevin R.; Swanson, Ronald V.; Zinder, Steven H.; Lander, Eric; Metcalf, William W.; Birren, Bruce, Allen, Nicole, Brown, Adam, Atnoor, Deven, Smirnov, Serge, Engels, Reinhard, Calvo, Sarah, FitzHugh, Will, Macdonald, Pendexter, Endrizzi, Matthew G., Roy, Alice, Nusbaum, Chad, McEwan, Paul, Zimmer, Andrew, Ye, Wenjuan, Tirrell, Andrea, Talamas, Jessica, and McKernan, Kevin

Subjects
Methanobacteriaceae -- Research, Archaeabacteria -- Research, Nucleotide sequence -- Research, Genomes -- Research, Genetic research, Health
Abstract

The complete genome sequence of an acetate-utilizing methanogen, Methanosarcina acetivorans C2A is presented. The availability of genetic methods, coupled with its physiological and metabolic diversity, makes M. acetivorans a powerful model organism for the study of archaeal biology.

Published
2002

33. Deep-transcriptome and ribonome sequencing redefines the molecular networks of pluripotency and the extracellular space in human embryonic stem cells

Author

Kolle, Gabriel, Shepherd, Jill L, Gardiner, Brooke, Kassahn, Karin, Cloonan, Nicole, Wood, David L, Nourbakhsh, Ehsan, Taylor, Darren F, Wani, Shivangi, Chy, Hun S, Zhou, Qi, McKernan, Kevin, Kuersten, Scott, Laslett, Andrew L, Grimmond, Sean M, Kolle, Gabriel, Shepherd, Jill L, Gardiner, Brooke, Kassahn, Karin, Cloonan, Nicole, Wood, David L, Nourbakhsh, Ehsan, Taylor, Darren F, Wani, Shivangi, Chy, Hun S, Zhou, Qi, McKernan, Kevin, Kuersten, Scott, Laslett, Andrew L, and Grimmond, Sean M

Abstract

Recent RNA-sequencing studies have shown remarkable complexity in the mammalian transcriptome. The ultimate impact of this complexity on the predicted proteomic output is less well defined. We have undertaken strand-specific RNA sequencing of multiple cellular RNA fractions (>20 Gb) to uncover the transcriptional complexity of human embryonic stem cells (hESCs). We have shown that human embryonic stem (ES) cells display a high degree of transcriptional diversity, with more than half of active genes generating RNAs that differ from conventional gene models. We found evidence that more than 1000 genes express long 5′ and/or extended 3′UTRs, which was confirmed by “virtual Northern” analysis. Exhaustive sequencing of the membrane-polysome and cytosolic/untranslated fractions of hESCs was used to identify RNAs encoding peptides destined for secretion and the extracellular space and to demonstrate preferential selection of transcription complexity for translation in vitro. The impact of this newly defined complexity on known gene-centric network models such as the Plurinet and the cell surface signaling machinery in human ES cells revealed a significant expansion of known transcript isoforms at play, many predicting possible alternative functions based on sequence alterations within key functional domains.

Published
2011

34. MicroRNAs and their isomiRs function cooperatively to target common biological pathways

Author

Cloonan, Nicole, Wani, Shivangi, Xu, Qinying, Gu, Jian, Lea, Kristi, Heater, Sheila, Barbaciouru, Catalin, Steptoe, Anita, Martin, Hilary, Nourbakhsh, Ehsan, Krishnan, Keerthana, Gardiner, Brooke, Wang, Xiaohui, Nones, Katia, Steen, Jason A, Matigan, Nick A, Wood, Dave L, Kasshan, Karin, Waddell, Nic, Shepherd, Jill L, Lee, Clarence, Ichikawa, Jeff, McKernan, Kevin, Bramlett, Kelli, Kuersten, Scott, Grimmond, Sean M, Cloonan, Nicole, Wani, Shivangi, Xu, Qinying, Gu, Jian, Lea, Kristi, Heater, Sheila, Barbaciouru, Catalin, Steptoe, Anita, Martin, Hilary, Nourbakhsh, Ehsan, Krishnan, Keerthana, Gardiner, Brooke, Wang, Xiaohui, Nones, Katia, Steen, Jason A, Matigan, Nick A, Wood, Dave L, Kasshan, Karin, Waddell, Nic, Shepherd, Jill L, Lee, Clarence, Ichikawa, Jeff, McKernan, Kevin, Bramlett, Kelli, Kuersten, Scott, and Grimmond, Sean M

Abstract

Background: Variants of microRNAs (miRNAs), called isomiRs, are commonly reported in deep-sequencing studies; however, the functional significance of these variants remains controversial. Observational studies show that isomiR patterns are non-random, hinting that these molecules could be regulated and therefore functional, although no conclusive biological role has been demonstrated for these molecules. Results: To assess the biological relevance of isomiRs, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline called miRNA-MATE to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. A large proportion of isomiRs potentially derive from AGO2 cleavage independent of Dicer. We isolated polyribosome-associated mRNA, captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies allow us to experimentally determine genome-wide mRNA targets, and these experiments showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs. Conclusions: Together, these results find isomiRs to be biologically relevant and functionally cooperative partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur when the specificity of miRNA targeting is mediated by only 6 to 11 nucleotides.

Published
2011

35. Differential binding and co-binding pattern of FOXA1 and FOXA3 and their relation to H3K4me3 in HepG2 cells revealed by ChIP-seq

Author

Motallebipour, Mehdi, Ameur, Adam, Bysani, Madhusudhan Reddy, Patra, Kalicharan, Wallerman, Ola, Mangion, Jonathan, Barker, Melissa, McKernan, Kevin, Komorowski, Jan, Wadelius, Claes, Motallebipour, Mehdi, Ameur, Adam, Bysani, Madhusudhan Reddy, Patra, Kalicharan, Wallerman, Ola, Mangion, Jonathan, Barker, Melissa, McKernan, Kevin, Komorowski, Jan, and Wadelius, Claes

Abstract

BACKGROUND: The forkhead box/winged helix family members FOXA1, FOXA2, and FOXA3 are of high importance in development and specification of the hepatic linage and the continued expression of liver-specific genes. RESULTS: Here, we present a genome-wide location analysis of FOXA1 and FOXA3 binding sites in HepG2 cells through chromatin immunoprecipitation with detection by sequencing (ChIP-seq) studies and compare these with our previous results on FOXA2. We found that these factors often bind close to each other in different combinations and consecutive immunoprecipitation of chromatin for one and then a second factor (ChIP-reChIP) shows that this occurs in the same cell and on the same DNA molecule, suggestive of molecular interactions. Using co-immunoprecipitation, we further show that FOXA2 interacts with both FOXA1 and FOXA3 in vivo, while FOXA1 and FOXA3 do not appear to interact. Additionally, we detected diverse patterns of trimethylation of lysine 4 on histone H3 (H3K4me3) at transcriptional start sites and directionality of this modification at FOXA binding sites. Using the sequence reads at polymorphic positions, we were able to predict allele specific binding for FOXA1, FOXA3, and H3K4me3. Finally, several SNPs associated with diseases and quantitative traits were located in the enriched regions. CONCLUSIONS: We find that ChIP-seq can be used not only to create gene regulatory maps but also to predict molecular interactions and to inform on the mechanisms for common quantitative variation., De två (2) första författarna delar förstaförfattarskapet.

Published
2009
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37. Deep-transcriptome and ribonome sequencing redefines the molecular networks of pluripotency and the extracellular space in human embryonic stem cells

Author

Kolle, Gabriel, primary, Shepherd, Jill L., additional, Gardiner, Brooke, additional, Kassahn, Karin S., additional, Cloonan, Nicole, additional, Wood, David L.A., additional, Nourbakhsh, Ehsan, additional, Taylor, Darrin F., additional, Wani, Shivangi, additional, Chy, Hun S., additional, Zhou, Qi, additional, McKernan, Kevin, additional, Kuersten, Scott, additional, Laslett, Andrew L., additional, and Grimmond, Sean M., additional

Published
2011
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38. Whole Genome Sequence of a Crohn Disease Trio – A Paradigm for Individualized Disease Etiology Discovery

Author

Rosenstiel, Philip C., primary, Barann, Matthias, additional, Franke, Andre, additional, Stade, Bjoern, additional, Thomsen, Ingo, additional, Schilhabel, Markus B., additional, Sheth, Vrunda, additional, Lee, Clarence, additional, Klostermeier, Ulrich C., additional, McKernan, Kevin, additional, Fritscher-Ravens, Annette, additional, and Schreiber, Stefan, additional

Published
2011
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41. A small-cell lung cancer genome with complex signatures of tobacco exposure

Author

Pleasance, Erin D., primary, Stephens, Philip J., additional, O’Meara, Sarah, additional, McBride, David J., additional, Meynert, Alison, additional, Jones, David, additional, Lin, Meng-Lay, additional, Beare, David, additional, Lau, King Wai, additional, Greenman, Chris, additional, Varela, Ignacio, additional, Nik-Zainal, Serena, additional, Davies, Helen R., additional, Ordoñez, Gonzalo R., additional, Mudie, Laura J., additional, Latimer, Calli, additional, Edkins, Sarah, additional, Stebbings, Lucy, additional, Chen, Lina, additional, Jia, Mingming, additional, Leroy, Catherine, additional, Marshall, John, additional, Menzies, Andrew, additional, Butler, Adam, additional, Teague, Jon W., additional, Mangion, Jonathon, additional, Sun, Yongming A., additional, McLaughlin, Stephen F., additional, Peckham, Heather E., additional, Tsung, Eric F., additional, Costa, Gina L., additional, Lee, Clarence C., additional, Minna, John D., additional, Gazdar, Adi, additional, Birney, Ewan, additional, Rhodes, Michael D., additional, McKernan, Kevin J., additional, Stratton, Michael R., additional, Futreal, P. Andrew, additional, and Campbell, Peter J., additional

Published
2009
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42. A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning

Author

Valouev, Anton, primary, Ichikawa, Jeffrey, additional, Tonthat, Thaisan, additional, Stuart, Jeremy, additional, Ranade, Swati, additional, Peckham, Heather, additional, Zeng, Kathy, additional, Malek, Joel A., additional, Costa, Gina, additional, McKernan, Kevin, additional, Sidow, Arend, additional, Fire, Andrew, additional, and Johnson, Steven M., additional

Published
2008
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43. Whole Methylome Analysis by Ultra-Deep Sequencing Using Two-Base Encoding.

Author

Chung, Christina A. Bormann, Boyd, Victoria L., McKernan, Kevin J., Yutao Fu, Monighetti, Cinna, Peckham, Heather E., and Barker, Melissa

Subjects
METHYLATION, ALKYLATION, THYMINE, URACIL, DNA, DEOXYRIBOSE, NUCLEIC acids, GENE expression, GENOMES, GENOMICS
Abstract

Methylation, the addition of methyl groups to cytosine (C), plays an important role in the regulation of gene expression in both normal and dysfunctional cells. During bisulfite conversion and subsequent PCR amplification, unmethylated Cs are converted into thymine (T), while methylated Cs will not be converted. Sequencing of this bisulfite-treated DNA permits the detection of methylation at specific sites. Through the introduction of next-generation sequencing technologies (NGS) simultaneous analysis of methylation motifs in multiple regions provides the opportunity for hypothesis-free study of the entire methylome. Here we present a whole methylome sequencing study that compares two different bisulfite conversion methods (in solution versus in gel), utilizing the high throughput of the SOLiD™ System. Advantages and disadvantages of the two different bisulfite conversion methods for constructing sequencing libraries are discussed. Furthermore, the application of the SOLiD™ bisulfite sequencing to larger and more complex genomes is shown with preliminary in silico created bisulfite converted reads. [ABSTRACT FROM AUTHOR]

Published
2010
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44. ALLPATHS 2: Small Genomes Assembled Accurately and with High Continuity from Short Paired Reads

Author

MacCallum, Iain, Przybylski, Dariusz, Gnerre, Sante, Burton, Joshua, Gnirke, Andreas, Malek, Joel, McKernan, Kevin, Ranade, Swati, Shea, Terrance P, Williams, Louise, Nusbaum, Chad, Jaffe, David B, Shlyakhter, Ilya, and Young, Sarah

Abstract

We demonstrate that genome sequences approaching finished quality can be generated from short paired reads. Using 36 base (fragment) and 26 base (jumping) reads from five microbial genomes of varied GC composition and sizes up to 40 Mb, ALLPATHS2 generated assemblies with long, accurate contigs and scaffolds. Velvet and EULER-SR were less accurate. For example, for Escherichia coli, the fraction of 10-kb stretches that were perfect was 99.8% (ALLPATHS2), 68.7% (Velvet), and 42.1% (EULER-SR)., Organismic and Evolutionary Biology, Version of Record

Published
2009
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45. Strand-based mixture modeling of nucleosome positioning in HepG2 cells and their regulatory dynamics in response to TGF-beta treatment

Author

Andersson, Robin, Enroth, Stefan, Barbacioru, Catalin, Reddy Bysani, Madhu Sudhan, Wallerman, Ola, Tuch, Brian, Lee, Clarence, Peckham, Heather, McKernan, Kevin, de la Vega, Francisco, Komorowski, Jan, Wadelius, Claes, Andersson, Robin, Enroth, Stefan, Barbacioru, Catalin, Reddy Bysani, Madhu Sudhan, Wallerman, Ola, Tuch, Brian, Lee, Clarence, Peckham, Heather, McKernan, Kevin, de la Vega, Francisco, Komorowski, Jan, and Wadelius, Claes

46. Demographic history and rare allele sharing among human populations

Author

Gravel, Simon, Henn, Brenna M., Gutenkunst, Ryan N., Indap, Amit R., Marth, Gabor T., Clark, Andrew G., Yu, Fuli, Gibbs, Richard A., Bustamante, Carlos D., Altshuler, David L., Durbin, Richard M., Abecasis, Gonçalo R., Bentley, David R., Chakravarti, Aravinda, Collins, Francis S., De La Vega, Francisco M., Donnelly, Peter, Egholm, Michael, Flicek, Paul, Gabriel, Stacey B., Knoppers, Bartha M., Lander, Eric S., Lehrach, Hans, Mardis, Elaine R., McVean, Gil A., Nickerson, Debbie A., Peltonen, Leena, Schafer, Alan J., Sherry, Stephen T., Wang, Jun, Wilson, Richard K., Deiros, David, Metzker, Mike, Muzny, Donna, Reid, Jeff, Wheeler, David, Li, Jingxiang, Jian, Min, Li, Guoqing, Li, Ruiqiang, Liang, Huiqing, Tian, Geng, Wang, Bo, Wang, Jian, Wang, Wei, Yang, Huanming, Zhang, Xiuqing, Zheng, Huisong, Ambrogio, Lauren, Bloom, Toby, Cibulskis, Kristian, Fennell, Tim J., Jaffe, David B., Shefler, Erica, Sougnez, Carrie L., Gormley, Niall, Humphray, Sean, Kingsbury, Zoya, Koko-Gonzales, Paula, Stone, Jennifer, McKernan, Kevin J., Costa, Gina L., Ichikawa, Jeffry K., Lee, Clarence C., Sudbrak, Ralf, Borodina, Tatiana A., Dahl, Andreas, Davydov, Alexey N., Marquardt, Peter, Mertes, Florian, Nietfeld, Wilfiried, Rosenstiel, Philip, Schreiber, Stefan, Soldatov, Aleksey V., Timmermann, Bernd, Tolzmann, Marius, Affourtit, Jason, Ashworth, Dana, Attiya, Said, Bachorski, Melissa, Buglione, Eli, Burke, Adam, Caprio, Amanda, Celone, Christopher, Clark, Shauna, Conners, David, Desany, Brian, Gu, Lisa, Guccione, Lorri, Kao, Kalvin, Kebbel, Andrew, Knowlton, Jennifer, Labrecque, Matthew, McDade, Louise, Mealmaker, Craig, Minderman, Melissa, Nawrocki, Anne, Niazi, Faheem, Pareja, Kristen, Ramenani, Ravi, Riches, David, Song, Wanmin, Turcotte, Cynthia, Wang, Shally, Dooling, David, Fulton, Lucinda, Fulton, Robert, Weinstock, George, Burton, John, Carter, David M., Churcher, Carol, Coffey, Alison, Cox, Anthony, Palotie, Aarno, Quail, Michael, Skelly, Tom, Stalker, James, Swerdlow, Harold P., Turner, Daniel, De Witte, Anniek, Giles, Shane, Bainbridge, Matthew, Challis, Danny, Sabo, Aniko, Yu, Jin, Fang, Xiaodong, Guo, Xiaosen, Li, Yingrui, Luo, Ruibang, Tai, Shuaishuai, Wu, Honglong, Zheng, Hancheng, Zheng, Xiaole, Zhou, Yan, Garrison, Erik P., Huang, Weichun, Indap, Amit, Kural, Deniz, Lee, Wan-Ping, Leong, Wen Fung, Quinlan, Aaron R., Stewart, Chip, Stromberg, Michael P., Ward, Alistair N., Wu, Jiantao, Lee, Charles, Mills, Ryan E., Shi, Xinghua, Daly, Mark J., DePristo, Mark A., Ball, Aaron D., Banks, Eric, Browning, Brian L., Garimella, Kiran V., Grossman, Sharon R., Handsaker, Robert E., Hanna, Matt, Hartl, Chris, Kernytsky, Andrew M., Korn, Joshua M., Li, Heng, Maguire, Jared R., McCarroll, Steven A., McKenna, Aaron, Nemesh, James C., Philippakis, Anthony A., Poplin, Ryan E., Price, Alkes, Rivas, Manuel A., Sabeti, Pardis C., Schaffner, Stephen F., Shlyakhter, Ilya A., Cooper, David N., Ball, Edward V., Mort, Matthew, Phillips, Andrew D., Stenson, Peter D., Sebat, Jonathan, Makarov, Vladimir, Ye, Kenny, Yoon, Seungtai C., Boyko, Adam, Degenhardt, Jeremiah, Kaganovich, Mark, Keinan, Alon, Lacroute, Phil, Ma, Xin, Reynolds, Andy, Clarke, Laura, Cunningham, Fiona, Herrero, Javier, Keenen, Stephen, Kulesha, Eugene, Leinonen, Rasko, McLaren, William M., Radhakrishnan, Rajesh, Smith, Richard E., Zalunin, Vadim, Zheng-Bradley, Xiangqun, Korbel, Jan O., Stütz, Adrian M., Bauer, Markus, Cheetham, R. Keira, Cox, Tony, Eberle, Michael, James, Terena, Kahn, Scott, Murray, Lisa, Ye, Kai, Fu, Yutao, Hyland, Fiona C. L., Manning, Jonathan M., McLaughlin, Stephen F., Peckham, Heather E., Sakarya, Onur, Sun, Yongming A., Tsung, Eric F., Batzer, Mark A., Konkel, Miriam K., Walker, Jerilyn A., Albrecht, Marcus W., Amstislavskiy, Vyacheslav S., Herwig, Ralf, Parkhomchuk, Dimitri V., Agarwala, Richa, Khouri, Hoda M., Morgulis, Aleksandr O., Paschall, Justin E., Phan, Lon D., Rotmistrovsky, Kirill E., Sanders, Robert D., Shumway, Martin F., Xiao, Chunlin, Auton, Adam, Iqbal, Zamin, Lunter, Gerton, Marchini, Jonathan L., Moutsianas, Loukas, Myers, Simon, Tumian, Afidalina, Knight, James, Winer, Roger, Craig, David W., Beckstrom-Sternberg, Steve M., Christoforides, Alexis, Kurdoglu, Ahmet A., Pearson, John V., Sinari, Shripad A., Tembe, Waibhav D., Haussler, David, Hinrichs, Angie S., Katzman, Sol J., Kern, Andrew, Kuhn, Robert M., Przeworski, Molly, Hernandez, Ryan D., Howie, Bryan, Kelley, Joanna L., Melton, S. Cord, Li, Yun, Anderson, Paul, Blackwell, Tom, Chen, Wei, Cookson, William O., Ding, Jun, Kang, Hyun Min, Lathrop, Mark, Liang, Liming, Moffatt, Miriam F., Scheet, Paul, Sidore, Carlo, Snyder, Matthew, Zhan, Xiaowei, Zöllner, Sebastian, Awadalla, Philip, Casals, Ferran, Idaghdour, Youssef, Keebler, John, Stone, Eric A., Zilversmit, Martine, Jorde, Lynn, Xing, Jinchuan, Eichler, Evan E., Aksay, Gozde, Alkan, Can, Hajirasouliha, Iman, Hormozdiari, Fereydoun, Kidd, Jeffrey M., Sahinalp, S. Cenk, Sudmant, Peter H., Chen, Ken, Chinwalla, Asif, Ding, Li, Koboldt, Daniel C., McLellan, Mike D., Wallis, John W., Wendl, Michael C., Zhang, Qunyuan, Albers, Cornelis A., Ayub, Qasim, Balasubramaniam, Senduran, Barrett, Jeffrey C., Chen, Yuan, Conrad, Donald F., Danecek, Petr, Dermitzakis, Emmanouil T., Hu, Min, Huang, Ni, Hurles, Matt E., Jin, Hanjun, Jostins, Luke, Keane, Thomas M., Le, Si Quang, Lindsay, Sarah, Long, Quan, MacArthur, Daniel G., Montgomery, Stephen B., Parts, Leopold, Tyler-Smith, Chris, Walter, Klaudia, Zhang, Yujun, Gerstein, Mark B., Snyder, Michael, Abyzov, Alexej, Balasubramanian, Suganthi, Bjornson, Robert, Du, Jiang, Grubert, Fabian, Habegger, Lukas, Haraksingh, Rajini, Jee, Justin, Khurana, Ekta, Lam, Hugo Y. K., Leng, Jing, Mu, Xinmeng Jasmine, Urban, Alexander E., Zhang, Zhengdong, Coafra, Cristian, Dinh, Huyen, Kovar, Christie, Lee, Sandy, Nazareth, Lynne, Wilkinson, Jane, Coffey, Allison, Scott, Carol, Gharani, Neda, Kaye, Jane S., Kent, Alastair, Li, Taosha, McGuire, Amy L., Ossorio, Pilar N., Rotimi, Charles N., Su, Yeyang, Toji, Lorraine H., TylerSmith, Chris, Brooks, Lisa D., Felsenfeld, Adam L., McEwen, Jean E., Abdallah, Assya, Juenger, Christopher R., Clemm, Nicholas C., Duncanson, Audrey, Green, Eric D., Guyer, Mark S., Peterson, Jane L., Gravel, Simon, Henn, Brenna M., Gutenkunst, Ryan N., Indap, Amit R., Marth, Gabor T., Clark, Andrew G., Yu, Fuli, Gibbs, Richard A., Bustamante, Carlos D., Altshuler, David L., Durbin, Richard M., Abecasis, Gonçalo R., Bentley, David R., Chakravarti, Aravinda, Collins, Francis S., De La Vega, Francisco M., Donnelly, Peter, Egholm, Michael, Flicek, Paul, Gabriel, Stacey B., Knoppers, Bartha M., Lander, Eric S., Lehrach, Hans, Mardis, Elaine R., McVean, Gil A., Nickerson, Debbie A., Peltonen, Leena, Schafer, Alan J., Sherry, Stephen T., Wang, Jun, Wilson, Richard K., Deiros, David, Metzker, Mike, Muzny, Donna, Reid, Jeff, Wheeler, David, Li, Jingxiang, Jian, Min, Li, Guoqing, Li, Ruiqiang, Liang, Huiqing, Tian, Geng, Wang, Bo, Wang, Jian, Wang, Wei, Yang, Huanming, Zhang, Xiuqing, Zheng, Huisong, Ambrogio, Lauren, Bloom, Toby, Cibulskis, Kristian, Fennell, Tim J., Jaffe, David B., Shefler, Erica, Sougnez, Carrie L., Gormley, Niall, Humphray, Sean, Kingsbury, Zoya, Koko-Gonzales, Paula, Stone, Jennifer, McKernan, Kevin J., Costa, Gina L., Ichikawa, Jeffry K., Lee, Clarence C., Sudbrak, Ralf, Borodina, Tatiana A., Dahl, Andreas, Davydov, Alexey N., Marquardt, Peter, Mertes, Florian, Nietfeld, Wilfiried, Rosenstiel, Philip, Schreiber, Stefan, Soldatov, Aleksey V., Timmermann, Bernd, Tolzmann, Marius, Affourtit, Jason, Ashworth, Dana, Attiya, Said, Bachorski, Melissa, Buglione, Eli, Burke, Adam, Caprio, Amanda, Celone, Christopher, Clark, Shauna, Conners, David, Desany, Brian, Gu, Lisa, Guccione, Lorri, Kao, Kalvin, Kebbel, Andrew, Knowlton, Jennifer, Labrecque, Matthew, McDade, Louise, Mealmaker, Craig, Minderman, Melissa, Nawrocki, Anne, Niazi, Faheem, Pareja, Kristen, Ramenani, Ravi, Riches, David, Song, Wanmin, Turcotte, Cynthia, Wang, Shally, Dooling, David, Fulton, Lucinda, Fulton, Robert, Weinstock, George, Burton, John, Carter, David M., Churcher, Carol, Coffey, Alison, Cox, Anthony, Palotie, Aarno, Quail, Michael, Skelly, Tom, Stalker, James, Swerdlow, Harold P., Turner, Daniel, De Witte, Anniek, Giles, Shane, Bainbridge, Matthew, Challis, Danny, Sabo, Aniko, Yu, Jin, Fang, Xiaodong, Guo, Xiaosen, Li, Yingrui, Luo, Ruibang, Tai, Shuaishuai, Wu, Honglong, Zheng, Hancheng, Zheng, Xiaole, Zhou, Yan, Garrison, Erik P., Huang, Weichun, Indap, Amit, Kural, Deniz, Lee, Wan-Ping, Leong, Wen Fung, Quinlan, Aaron R., Stewart, Chip, Stromberg, Michael P., Ward, Alistair N., Wu, Jiantao, Lee, Charles, Mills, Ryan E., Shi, Xinghua, Daly, Mark J., DePristo, Mark A., Ball, Aaron D., Banks, Eric, Browning, Brian L., Garimella, Kiran V., Grossman, Sharon R., Handsaker, Robert E., Hanna, Matt, Hartl, Chris, Kernytsky, Andrew M., Korn, Joshua M., Li, Heng, Maguire, Jared R., McCarroll, Steven A., McKenna, Aaron, Nemesh, James C., Philippakis, Anthony A., Poplin, Ryan E., Price, Alkes, Rivas, Manuel A., Sabeti, Pardis C., Schaffner, Stephen F., Shlyakhter, Ilya A., Cooper, David N., Ball, Edward V., Mort, Matthew, Phillips, Andrew D., Stenson, Peter D., Sebat, Jonathan, Makarov, Vladimir, Ye, Kenny, Yoon, Seungtai C., Boyko, Adam, Degenhardt, Jeremiah, Kaganovich, Mark, Keinan, Alon, Lacroute, Phil, Ma, Xin, Reynolds, Andy, Clarke, Laura, Cunningham, Fiona, Herrero, Javier, Keenen, Stephen, Kulesha, Eugene, Leinonen, Rasko, McLaren, William M., Radhakrishnan, Rajesh, Smith, Richard E., Zalunin, Vadim, Zheng-Bradley, Xiangqun, Korbel, Jan O., Stütz, Adrian M., Bauer, Markus, Cheetham, R. Keira, Cox, Tony, Eberle, Michael, James, Terena, Kahn, Scott, Murray, Lisa, Ye, Kai, Fu, Yutao, Hyland, Fiona C. L., Manning, Jonathan M., McLaughlin, Stephen F., Peckham, Heather E., Sakarya, Onur, Sun, Yongming A., Tsung, Eric F., Batzer, Mark A., Konkel, Miriam K., Walker, Jerilyn A., Albrecht, Marcus W., Amstislavskiy, Vyacheslav S., Herwig, Ralf, Parkhomchuk, Dimitri V., Agarwala, Richa, Khouri, Hoda M., Morgulis, Aleksandr O., Paschall, Justin E., Phan, Lon D., Rotmistrovsky, Kirill E., Sanders, Robert D., Shumway, Martin F., Xiao, Chunlin, Auton, Adam, Iqbal, Zamin, Lunter, Gerton, Marchini, Jonathan L., Moutsianas, Loukas, Myers, Simon, Tumian, Afidalina, Knight, James, Winer, Roger, Craig, David W., Beckstrom-Sternberg, Steve M., Christoforides, Alexis, Kurdoglu, Ahmet A., Pearson, John V., Sinari, Shripad A., Tembe, Waibhav D., Haussler, David, Hinrichs, Angie S., Katzman, Sol J., Kern, Andrew, Kuhn, Robert M., Przeworski, Molly, Hernandez, Ryan D., Howie, Bryan, Kelley, Joanna L., Melton, S. Cord, Li, Yun, Anderson, Paul, Blackwell, Tom, Chen, Wei, Cookson, William O., Ding, Jun, Kang, Hyun Min, Lathrop, Mark, Liang, Liming, Moffatt, Miriam F., Scheet, Paul, Sidore, Carlo, Snyder, Matthew, Zhan, Xiaowei, Zöllner, Sebastian, Awadalla, Philip, Casals, Ferran, Idaghdour, Youssef, Keebler, John, Stone, Eric A., Zilversmit, Martine, Jorde, Lynn, Xing, Jinchuan, Eichler, Evan E., Aksay, Gozde, Alkan, Can, Hajirasouliha, Iman, Hormozdiari, Fereydoun, Kidd, Jeffrey M., Sahinalp, S. Cenk, Sudmant, Peter H., Chen, Ken, Chinwalla, Asif, Ding, Li, Koboldt, Daniel C., McLellan, Mike D., Wallis, John W., Wendl, Michael C., Zhang, Qunyuan, Albers, Cornelis A., Ayub, Qasim, Balasubramaniam, Senduran, Barrett, Jeffrey C., Chen, Yuan, Conrad, Donald F., Danecek, Petr, Dermitzakis, Emmanouil T., Hu, Min, Huang, Ni, Hurles, Matt E., Jin, Hanjun, Jostins, Luke, Keane, Thomas M., Le, Si Quang, Lindsay, Sarah, Long, Quan, MacArthur, Daniel G., Montgomery, Stephen B., Parts, Leopold, Tyler-Smith, Chris, Walter, Klaudia, Zhang, Yujun, Gerstein, Mark B., Snyder, Michael, Abyzov, Alexej, Balasubramanian, Suganthi, Bjornson, Robert, Du, Jiang, Grubert, Fabian, Habegger, Lukas, Haraksingh, Rajini, Jee, Justin, Khurana, Ekta, Lam, Hugo Y. K., Leng, Jing, Mu, Xinmeng Jasmine, Urban, Alexander E., Zhang, Zhengdong, Coafra, Cristian, Dinh, Huyen, Kovar, Christie, Lee, Sandy, Nazareth, Lynne, Wilkinson, Jane, Coffey, Allison, Scott, Carol, Gharani, Neda, Kaye, Jane S., Kent, Alastair, Li, Taosha, McGuire, Amy L., Ossorio, Pilar N., Rotimi, Charles N., Su, Yeyang, Toji, Lorraine H., TylerSmith, Chris, Brooks, Lisa D., Felsenfeld, Adam L., McEwen, Jean E., Abdallah, Assya, Juenger, Christopher R., Clemm, Nicholas C., Duncanson, Audrey, Green, Eric D., Guyer, Mark S., and Peterson, Jane L.

Abstract

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.

47. A Proteogenomics Approach.

Author

McKernan, Kevin

Subjects
*GENOMICS, *DRUG target, *GENETIC polymorphisms
Abstract

Editorial. Focuses on the application of proteogenomics approach in Human Genome Project. Determination of proteome expression levels and drug targets; Integration of pharmacogenomics with protein interactions; Analysis of genomic polymorphisms in genes.

Published
2002

48. Genotyping System Provides a Solution For SNP-Based Studies.

Author

McEwan, Paul and McKernan, Kevin

Subjects
*NUCLEOTIDES, *GENOMES
Abstract

Focuses on the discovery of single nucleotide polymorphism markers across the genome. Development of Whole Genome Shotgun sequencing; Offers of pharmaceutical development by the Agencourt Bioscience Corp; Synthesis of oligonucleotide primers.

Published
2002

49. MicroRNAs and their isomiRs function cooperatively to target common biological pathways.

Author

Cloonan N, Wani S, Xu Q, Gu J, Lea K, Heater S, Barbacioru C, Steptoe AL, Martin HC, Nourbakhsh E, Krishnan K, Gardiner B, Wang X, Nones K, Steen JA, Matigian NA, Wood DL, Kassahn KS, Waddell N, Shepherd J, Lee C, Ichikawa J, McKernan K, Bramlett K, Kuersten S, and Grimmond SM

Subjects
Base Sequence, Biotinylation, DEAD-box RNA Helicases genetics, Gene Expression Profiling, HEK293 Cells, HeLa Cells, High-Throughput Nucleotide Sequencing, Humans, MicroRNAs classification, MicroRNAs isolation & purification, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Ribonuclease III genetics, Sequence Alignment, Transcriptome, Transfection, Argonaute Proteins genetics, Gene Regulatory Networks genetics, MicroRNAs genetics, RNA, Messenger genetics
Abstract

Background: Variants of microRNAs (miRNAs), called isomiRs, are commonly reported in deep-sequencing studies; however, the functional significance of these variants remains controversial. Observational studies show that isomiR patterns are non-random, hinting that these molecules could be regulated and therefore functional, although no conclusive biological role has been demonstrated for these molecules., Results: To assess the biological relevance of isomiRs, we have performed ultra-deep miRNA-seq on ten adult human tissues, and created an analysis pipeline called miRNA-MATE to align, annotate, and analyze miRNAs and their isomiRs. We find that isomiRs share sequence and expression characteristics with canonical miRNAs, and are generally strongly correlated with canonical miRNA expression. A large proportion of isomiRs potentially derive from AGO2 cleavage independent of Dicer. We isolated polyribosome-associated mRNA, captured the mRNA-bound miRNAs, and found that isomiRs and canonical miRNAs are equally associated with translational machinery. Finally, we transfected cells with biotinylated RNA duplexes encoding isomiRs or their canonical counterparts and directly assayed their mRNA targets. These studies allow us to experimentally determine genome-wide mRNA targets, and these experiments showed substantial overlap in functional mRNA networks suppressed by both canonical miRNAs and their isomiRs., Conclusions: Together, these results find isomiRs to be biologically relevant and functionally cooperative partners of canonical miRNAs that act coordinately to target pathways of functionally related genes. This work exposes the complexity of the miRNA-transcriptome, and helps explain a major miRNA paradox: how specific regulation of biological processes can occur when the specificity of miRNA targeting is mediated by only 6 to 11 nucleotides.

Published
2011
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50. Polymorphism discovery in high-throughput resequenced microarray-enriched human genomic loci.

Author

Antipova AA, Sokolsky TD, Clouser CR, Dimalanta ET, Hendrickson CL, Kosnopo C, Lee CC, Ranade SS, Zhang L, Blanchard AP, and McKernan KJ

Subjects
Base Sequence, Biomedical Technology methods, Exons, Genetic Variation, Genome, Human, Heterozygote, Homozygote, Humans, Molecular Sequence Data, Mutation, Oligonucleotide Array Sequence Analysis, Polymorphism, Genetic, Sequence Analysis, DNA methods
Abstract

Identifying genetic variants and mutations that underlie human diseases requires development of robust, cost-effective tools for routine resequencing of regions of interest in the human genome. Here, we demonstrate that coupling Applied Biosystems SOLiD system-sequencing platform with microarray capture of targeted regions provides an efficient and robust method for high-coverage resequencing and polymorphism discovery in human protein-coding exons.

Published
2009

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