Browsing by Subject "Molecular Sequence Annotation"
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Item Open Access A high-resolution map of human evolutionary constraint using 29 mammals.(Nature, 2011-10-12) Lindblad-Toh, Kerstin; Garber, Manuel; Zuk, Or; Lin, Michael F; Parker, Brian J; Washietl, Stefan; Kheradpour, Pouya; Ernst, Jason; Jordan, Gregory; Mauceli, Evan; Ward, Lucas D; Lowe, Craig B; Holloway, Alisha K; Clamp, Michele; Gnerre, Sante; Alföldi, Jessica; Beal, Kathryn; Chang, Jean; Clawson, Hiram; Cuff, James; Di Palma, Federica; Fitzgerald, Stephen; Flicek, Paul; Guttman, Mitchell; Hubisz, Melissa J; Jaffe, David B; Jungreis, Irwin; Kent, W James; Kostka, Dennis; Lara, Marcia; Martins, Andre L; Massingham, Tim; Moltke, Ida; Raney, Brian J; Rasmussen, Matthew D; Robinson, Jim; Stark, Alexander; Vilella, Albert J; Wen, Jiayu; Xie, Xiaohui; Zody, Michael C; Broad Institute Sequencing Platform and Whole Genome Assembly Team; Baldwin, Jen; Bloom, Toby; Chin, Chee Whye; Heiman, Dave; Nicol, Robert; Nusbaum, Chad; Young, Sarah; Wilkinson, Jane; Worley, Kim C; Kovar, Christie L; Muzny, Donna M; Gibbs, Richard A; Baylor College of Medicine Human Genome Sequencing Center Sequencing Team; Cree, Andrew; Dihn, Huyen H; Fowler, Gerald; Jhangiani, Shalili; Joshi, Vandita; Lee, Sandra; Lewis, Lora R; Nazareth, Lynne V; Okwuonu, Geoffrey; Santibanez, Jireh; Warren, Wesley C; Mardis, Elaine R; Weinstock, George M; Wilson, Richard K; Genome Institute at Washington University; Delehaunty, Kim; Dooling, David; Fronik, Catrina; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Minx, Patrick; Sodergren, Erica; Birney, Ewan; Margulies, Elliott H; Herrero, Javier; Green, Eric D; Haussler, David; Siepel, Adam; Goldman, Nick; Pollard, Katherine S; Pedersen, Jakob S; Lander, Eric S; Kellis, ManolisThe comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.Item Open Access Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: a pathway-based analysis from published GWASs.(Scientific reports, 2017-03-17) Pan, Yongchu; Liu, Hongliang; Wang, Yanru; Kang, Xiaozheng; Liu, Zhensheng; Owzar, Kouros; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J; Brhane, Yonathan; McLaughlin, John; Brennan, Paul; Bickeböller, Heike; Rosenberger, Albert; Houlston, Richard S; Caporaso, Neil; Teresa Landi, Maria; Heinrich, Joachim; Risch, Angela; Wu, Xifeng; Ye, Yuanqing; Christiani, David C; Amos, Christopher I; Wei, QingyimRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summary data from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6 and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The six novel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression in lymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shed new light on the role of mRNA splicing genes in the development of lung cancer.Item Open Access Comparative genomics reveals insights into avian genome evolution and adaptation.(Science, 2014-12-12) Zhang, Guojie; Li, Cai; Li, Qiye; Li, Bo; Larkin, Denis M; Lee, Chul; Storz, Jay F; Antunes, Agostinho; Greenwold, Matthew J; Meredith, Robert W; Ödeen, Anders; Cui, Jie; Zhou, Qi; Xu, Luohao; Pan, Hailin; Wang, Zongji; Jin, Lijun; Zhang, Pei; Hu, Haofu; Yang, Wei; Hu, Jiang; Xiao, Jin; Yang, Zhikai; Liu, Yang; Xie, Qiaolin; Yu, Hao; Lian, Jinmin; Wen, Ping; Zhang, Fang; Li, Hui; Zeng, Yongli; Xiong, Zijun; Liu, Shiping; Zhou, Long; Huang, Zhiyong; An, Na; Wang, Jie; Zheng, Qiumei; Xiong, Yingqi; Wang, Guangbiao; Wang, Bo; Wang, Jingjing; Fan, Yu; da Fonseca, Rute R; Alfaro-Núñez, Alonzo; Schubert, Mikkel; Orlando, Ludovic; Mourier, Tobias; Howard, Jason T; Ganapathy, Ganeshkumar; Pfenning, Andreas; Whitney, Osceola; Rivas, Miriam V; Hara, Erina; Smith, Julia; Farré, Marta; Narayan, Jitendra; Slavov, Gancho; Romanov, Michael N; Borges, Rui; Borges, Rui; Machado, João Paulo; Khan, Imran; Springer, Mark S; Gatesy, John; Hoffmann, Federico G; Opazo, Juan C; Håstad, Olle; Sawyer, Roger H; Kim, Heebal; Kim, Kyu-Won; Kim, Hyeon Jeong; Cho, Seoae; Li, Ning; Huang, Yinhua; Bruford, Michael W; Zhan, Xiangjiang; Dixon, Andrew; Bertelsen, Mads F; Derryberry, Elizabeth; Warren, Wesley; Wilson, Richard K; Li, Shengbin; Ray, David A; Green, Richard E; O'Brien, Stephen J; Griffin, Darren; Johnson, Warren E; Haussler, David; Ryder, Oliver A; Willerslev, Eske; Graves, Gary R; Alström, Per; Fjeldså, Jon; Mindell, David P; Edwards, Scott V; Braun, Edward L; Rahbek, Carsten; Burt, David W; Houde, Peter; Zhang, Yong; Yang, Huanming; Wang, Jian; Avian Genome Consortium; Jarvis, Erich D; Gilbert, M Thomas P; Wang, JunBirds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.Item Open Access Comparative genomics reveals molecular features unique to the songbird lineage.(BMC Genomics, 2014-12-13) Wirthlin, Morgan; Lovell, Peter V; Jarvis, Erich D; Mello, Claudio VBACKGROUND: Songbirds (oscine Passeriformes) are among the most diverse and successful vertebrate groups, comprising almost half of all known bird species. Identifying the genomic innovations that might be associated with this success, as well as with characteristic songbird traits such as vocal learning and the brain circuits that underlie this behavior, has proven difficult, in part due to the small number of avian genomes available until recently. Here we performed a comparative analysis of 48 avian genomes to identify genomic features that are unique to songbirds, as well as an initial assessment of function by investigating their tissue distribution and predicted protein domain structure. RESULTS: Using BLAT alignments and gene synteny analysis, we curated a large set of Ensembl gene models that were annotated as novel or duplicated in the most commonly studied songbird, the Zebra finch (Taeniopygia guttata), and then extended this analysis to 47 additional avian and 4 non-avian genomes. We identified 10 novel genes uniquely present in songbird genomes. A refined map of chromosomal synteny disruptions in the Zebra finch genome revealed that the majority of these novel genes localized to regions of genomic instability associated with apparent chromosomal breakpoints. Analyses of in situ hybridization and RNA-seq data revealed that a subset of songbird-unique genes is expressed in the brain and/or other tissues, and that 2 of these (YTHDC2L1 and TMRA) are highly differentially expressed in vocal learning-associated nuclei relative to the rest of the brain. CONCLUSIONS: Our study reveals novel genes unique to songbirds, including some that may subserve their unique vocal control system, substantially improves the quality of Zebra finch genome annotations, and contributes to a better understanding of how genomic features may have evolved in conjunction with the emergence of the songbird lineage.Item Open Access Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1.(Metallomics, 2010-01) Crider, Sarah E; Holbrook, Robert J; Franz, Katherine JPlatinum therapeutic agents are widely used in the treatment of several forms of cancer. Various mechanisms for the transport of the drugs have been proposed including passive diffusion across the cellular membrane and active transport via proteins. The copper transport protein Ctr1 is responsible for high affinity copper uptake but has also been implicated in the transport of cisplatin into cells. Human hCtr1 contains two methionine-rich Mets motifs on its extracellular N-terminus that are potential platinum-binding sites: the first one encompasses residues 7-14 with amino acid sequence Met-Gly-Met-Ser-Tyr-Met-Asp-Ser and the second one spans residues 39-46 with sequence Met-Met-Met-Met-Pro-Met-Thr-Phe. In these studies, we use liquid chromatography and mass spectrometry to compare the binding interactions between cisplatin, carboplatin and oxaliplatin with synthetic peptides corresponding to hCtr1 Mets motifs. The interactions of cisplatin and carboplatin with Met-rich motifs that contain three or more methionines result in removal of the carrier ligands of both platinum complexes. In contrast, oxaliplatin retains its cyclohexyldiamine ligand upon platinum coordination to the peptide.Item Open Access Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.(G3 (Bethesda, Md.), 2015-03-04) Leung, Wilson; Shaffer, Christopher D; Reed, Laura K; Smith, Sheryl T; Barshop, William; Dirkes, William; Dothager, Matthew; Lee, Paul; Wong, Jeannette; Xiong, David; Yuan, Han; Bedard, James EJ; Machone, Joshua F; Patterson, Seantay D; Price, Amber L; Turner, Bryce A; Robic, Srebrenka; Luippold, Erin K; McCartha, Shannon R; Walji, Tezin A; Walker, Chelsea A; Saville, Kenneth; Abrams, Marita K; Armstrong, Andrew R; Armstrong, William; Bailey, Robert J; Barberi, Chelsea R; Beck, Lauren R; Blaker, Amanda L; Blunden, Christopher E; Brand, Jordan P; Brock, Ethan J; Brooks, Dana W; Brown, Marie; Butzler, Sarah C; Clark, Eric M; Clark, Nicole B; Collins, Ashley A; Cotteleer, Rebecca J; Cullimore, Peterson R; Dawson, Seth G; Docking, Carter T; Dorsett, Sasha L; Dougherty, Grace A; Downey, Kaitlyn A; Drake, Andrew P; Earl, Erica K; Floyd, Trevor G; Forsyth, Joshua D; Foust, Jonathan D; Franchi, Spencer L; Geary, James F; Hanson, Cynthia K; Harding, Taylor S; Harris, Cameron B; Heckman, Jonathan M; Holderness, Heather L; Howey, Nicole A; Jacobs, Dontae A; Jewell, Elizabeth S; Kaisler, Maria; Karaska, Elizabeth A; Kehoe, James L; Koaches, Hannah C; Koehler, Jessica; Koenig, Dana; Kujawski, Alexander J; Kus, Jordan E; Lammers, Jennifer A; Leads, Rachel R; Leatherman, Emily C; Lippert, Rachel N; Messenger, Gregory S; Morrow, Adam T; Newcomb, Victoria; Plasman, Haley J; Potocny, Stephanie J; Powers, Michelle K; Reem, Rachel M; Rennhack, Jonathan P; Reynolds, Katherine R; Reynolds, Lyndsey A; Rhee, Dong K; Rivard, Allyson B; Ronk, Adam J; Rooney, Meghan B; Rubin, Lainey S; Salbert, Luke R; Saluja, Rasleen K; Schauder, Taylor; Schneiter, Allison R; Schulz, Robert W; Smith, Karl E; Spencer, Sarah; Swanson, Bryant R; Tache, Melissa A; Tewilliager, Ashley A; Tilot, Amanda K; VanEck, Eve; Villerot, Matthew M; Vylonis, Megan B; Watson, David T; Wurzler, Juliana A; Wysocki, Lauren M; Yalamanchili, Monica; Zaborowicz, Matthew A; Emerson, Julia A; Ortiz, Carlos; Deuschle, Frederic J; DiLorenzo, Lauren A; Goeller, Katie L; Macchi, Christopher R; Muller, Sarah E; Pasierb, Brittany D; Sable, Joseph E; Tucci, Jessica M; Tynon, Marykathryn; Dunbar, David A; Beken, Levent H; Conturso, Alaina C; Danner, Benjamin L; DeMichele, Gabriella A; Gonzales, Justin A; Hammond, Maureen S; Kelley, Colleen V; Kelly, Elisabeth A; Kulich, Danielle; Mageeney, Catherine M; McCabe, Nikie L; Newman, Alyssa M; Spaeder, Lindsay A; Tumminello, Richard A; Revie, Dennis; Benson, Jonathon M; Cristostomo, Michael C; DaSilva, Paolo A; Harker, Katherine S; Jarrell, Jenifer N; Jimenez, Luis A; Katz, Brandon M; Kennedy, William R; Kolibas, Kimberly S; LeBlanc, Mark T; Nguyen, Trung T; Nicolas, Daniel S; Patao, Melissa D; Patao, Shane M; Rupley, Bryan J; Sessions, Bridget J; Weaver, Jennifer A; Goodman, Anya L; Alvendia, Erica L; Baldassari, Shana M; Brown, Ashley S; Chase, Ian O; Chen, Maida; Chiang, Scott; Cromwell, Avery B; Custer, Ashley F; DiTommaso, Tia M; El-Adaimi, Jad; Goscinski, Nora C; Grove, Ryan A; Gutierrez, Nestor; Harnoto, Raechel S; Hedeen, Heather; Hong, Emily L; Hopkins, Barbara L; Huerta, Vilma F; Khoshabian, Colin; LaForge, Kristin M; Lee, Cassidy T; Lewis, Benjamin M; Lydon, Anniken M; Maniaci, Brian J; Mitchell, Ryan D; Morlock, Elaine V; Morris, William M; Naik, Priyanka; Olson, Nicole C; Osterloh, Jeannette M; Perez, Marcos A; Presley, Jonathan D; Randazzo, Matt J; Regan, Melanie K; Rossi, Franca G; Smith, Melanie A; Soliterman, Eugenia A; Sparks, Ciani J; Tran, Danny L; Wan, Tiffany; Welker, Anne A; Wong, Jeremy N; Sreenivasan, Aparna; Youngblom, Jim; Adams, Andrew; Alldredge, Justin; Bryant, Ashley; Carranza, David; Cifelli, Alyssa; Coulson, Kevin; Debow, Calise; Delacruz, Noelle; Emerson, Charlene; Farrar, Cassandra; Foret, Don; Garibay, Edgar; Gooch, John; Heslop, Michelle; Kaur, Sukhjit; Khan, Ambreen; Kim, Van; Lamb, Travis; Lindbeck, Peter; Lucas, Gabi; Macias, Elizabeth; Martiniuc, Daniela; Mayorga, Lissett; Medina, Joseph; Membreno, Nelson; Messiah, Shady; Neufeld, Lacey; Nguyen, San Francisco; Nichols, Zachary; Odisho, George; Peterson, Daymon; Rodela, Laura; Rodriguez, Priscilla; Rodriguez, Vanessa; Ruiz, Jorge; Sherrill, Will; Silva, Valeria; Sparks, Jeri; Statton, Geeta; Townsend, Ashley; Valdez, Isabel; Waters, Mary; Westphal, Kyle; Winkler, Stacey; Zumkehr, Joannee; DeJong, Randall J; Hoogewerf, Arlene J; Ackerman, Cheri M; Armistead, Isaac O; Baatenburg, Lara; Borr, Matthew J; Brouwer, Lindsay K; Burkhart, Brandon J; Bushhouse, Kelsey T; Cesko, Lejla; Choi, Tiffany YY; Cohen, Heather; Damsteegt, Amanda M; Darusz, Jess M; Dauphin, Cory M; Davis, Yelena P; Diekema, Emily J; Drewry, Melissa; Eisen, Michelle EM; Faber, Hayley M; Faber, Katherine J; Feenstra, Elizabeth; Felzer-Kim, Isabella T; Hammond, Brandy L; Hendriksma, Jesse; Herrold, Milton R; Hilbrands, Julia A; Howell, Emily J; Jelgerhuis, Sarah A; Jelsema, Timothy R; Johnson, Benjamin K; Jones, Kelly K; Kim, Anna; Kooienga, Ross D; Menyes, Erika E; Nollet, Eric A; Plescher, Brittany E; Rios, Lindsay; Rose, Jenny L; Schepers, Allison J; Scott, Geoff; Smith, Joshua R; Sterling, Allison M; Tenney, Jenna C; Uitvlugt, Chris; VanDyken, Rachel E; VanderVennen, Marielle; Vue, Samantha; Kokan, Nighat P; Agbley, Kwabea; Boham, Sampson K; Broomfield, Daniel; Chapman, Kayla; Dobbe, Ali; Dobbe, Ian; Harrington, William; Ibrahem, Marwan; Kennedy, Andre; Koplinsky, Chad A; Kubricky, Cassandra; Ladzekpo, Danielle; Pattison, Claire; Ramirez, Roman E; Wande, Lucia; Woehlke, Sarah; Wawersik, Matthew; Kiernan, Elizabeth; Thompson, Jeffrey S; Banker, Roxanne; Bartling, Justina R; Bhatiya, Chinmoy I; Boudoures, Anna L; Christiansen, Lena; Fosselman, Daniel S; French, Kristin M; Gill, Ishwar S; Havill, Jessen T; Johnson, Jaelyn L; Keny, Lauren J; Kerber, John M; Klett, Bethany M; Kufel, Christina N; May, Francis J; Mecoli, Jonathan P; Merry, Callie R; Meyer, Lauren R; Miller, Emily G; Mullen, Gregory J; Palozola, Katherine C; Pfeil, Jacob J; Thomas, Jessica G; Verbofsky, Evan M; Spana, Eric P; Agarwalla, Anant; Chapman, Julia; Chlebina, Ben; Chong, Insun; Falk, IN; Fitzgibbons, John D; Friedman, Harrison; Ighile, Osagie; Kim, Andrew J; Knouse, Kristin A; Kung, Faith; Mammo, Danny; Ng, Chun Leung; Nikam, Vinayak S; Norton, Diana; Pham, Philip; Polk, Jessica W; Prasad, Shreya; Rankin, Helen; Ratliff, Camille D; Scala, Victoria; Schwartz, Nicholas U; Shuen, Jessica A; Xu, Amy; Xu, Thomas Q; Zhang, Yi; Rosenwald, Anne G; Burg, Martin G; Adams, Stephanie J; Baker, Morgan; Botsford, Bobbi; Brinkley, Briana; Brown, Carter; Emiah, Shadie; Enoch, Erica; Gier, Chad; Greenwell, Alyson; Hoogenboom, Lindsay; Matthews, Jordan E; McDonald, Mitchell; Mercer, Amanda; Monsma, Nicholaus; Ostby, Kristine; Ramic, Alen; Shallman, Devon; Simon, Matthew; Spencer, Eric; Tomkins, Trisha; Wendland, Pete; Wylie, Anna; Wolyniak, Michael J; Robertson, Gregory M; Smith, Samuel I; DiAngelo, Justin R; Sassu, Eric D; Bhalla, Satish C; Sharif, Karim A; Choeying, Tenzin; Macias, Jason S; Sanusi, Fareed; Torchon, Karvyn; Bednarski, April E; Alvarez, Consuelo J; Davis, Kristen C; Dunham, Carrie A; Grantham, Alaina J; Hare, Amber N; Schottler, Jennifer; Scott, Zackary W; Kuleck, Gary A; Yu, Nicole S; Kaehler, Marian M; Jipp, Jacob; Overvoorde, Paul J; Shoop, Elizabeth; Cyrankowski, Olivia; Hoover, Betsy; Kusner, Matt; Lin, Devry; Martinov, Tijana; Misch, Jonathan; Salzman, Garrett; Schiedermayer, Holly; Snavely, Michael; Zarrasola, Stephanie; Parrish, Susan; Baker, Atlee; Beckett, Alissa; Belella, Carissa; Bryant, Julie; Conrad, Turner; Fearnow, Adam; Gomez, Carolina; Herbstsomer, Robert A; Hirsch, Sarah; Johnson, Christen; Jones, Melissa; Kabaso, Rita; Lemmon, Eric; Vieira, Carolina Marques Dos Santos; McFarland, Darryl; McLaughlin, Christopher; Morgan, Abbie; Musokotwane, Sepo; Neutzling, William; Nietmann, Jana; Paluskievicz, Christina; Penn, Jessica; Peoples, Emily; Pozmanter, Caitlin; Reed, Emily; Rigby, Nichole; Schmidt, Lasse; Shelton, Micah; Shuford, Rebecca; Tirasawasdichai, Tiara; Undem, Blair; Urick, Damian; Vondy, Kayla; Yarrington, Bryan; Eckdahl, Todd T; Poet, Jeffrey L; Allen, Alica B; Anderson, John E; Barnett, Jason M; Baumgardner, Jordan S; Brown, Adam D; Carney, Jordan E; Chavez, Ramiro A; Christgen, Shelbi L; Christie, Jordan S; Clary, Andrea N; Conn, Michel A; Cooper, Kristen M; Crowley, Matt J; Crowley, Samuel T; Doty, Jennifer S; Dow, Brian A; Edwards, Curtis R; Elder, Darcie D; Fanning, John P; Janssen, Bridget M; Lambright, Anthony K; Lane, Curtiss E; Limle, Austin B; Mazur, Tammy; McCracken, Marly R; McDonough, Alexa M; Melton, Amy D; Minnick, Phillip J; Musick, Adam E; Newhart, William H; Noynaert, Joseph W; Ogden, Bradley J; Sandusky, Michael W; Schmuecker, Samantha M; Shipman, Anna L; Smith, Anna L; Thomsen, Kristen M; Unzicker, Matthew R; Vernon, William B; Winn, Wesley W; Woyski, Dustin S; Zhu, Xiao; Du, Chunguang; Ament, Caitlin; Aso, Soham; Bisogno, Laura Simone; Caronna, Jason; Fefelova, Nadezhda; Lopez, Lenin; Malkowitz, Lorraine; Marra, Jonathan; Menillo, Daniella; Obiorah, Ifeanyi; Onsarigo, Eric Nyabeta; Primus, Shekerah; Soos, Mahdi; Tare, Archana; Zidan, Ameer; Jones, Christopher J; Aronhalt, Todd; Bellush, James M; Burke, Christa; DeFazio, Steve; Does, Benjamin R; Johnson, Todd D; Keysock, Nicholas; Knudsen, Nelson H; Messler, James; Myirski, Kevin; Rekai, Jade Lea; Rempe, Ryan Michael; Salgado, Michael S; Stagaard, Erica; Starcher, Justin R; Waggoner, Andrew W; Yemelyanova, Anastasia K; Hark, Amy T; Bertolet, Anne; Kuschner, Cyrus E; Parry, Kesley; Quach, Michael; Shantzer, Lindsey; Shaw, Mary E; Smith, Mary A; Glenn, Omolara; Mason, Portia; Williams, Charlotte; Key, S Catherine Silver; Henry, Tyneshia CP; Johnson, Ashlee G; White, Jackie X; Haberman, Adam; Asinof, Sam; Drumm, Kelly; Freeburg, Trip; Safa, Nadia; Schultz, Darrin; Shevin, Yakov; Svoronos, Petros; Vuong, Tam; Wellinghoff, Jules; Hoopes, Laura LM; Chau, Kim M; Ward, Alyssa; Regisford, E Gloria C; Augustine, LaJerald; Davis-Reyes, Brionna; Echendu, Vivienne; Hales, Jasmine; Ibarra, Sharon; Johnson, Lauriaun; Ovu, Steven; Braverman, John M; Bahr, Thomas J; Caesar, Nicole M; Campana, Christopher; Cassidy, Daniel W; Cognetti, Peter A; English, Johnathan D; Fadus, Matthew C; Fick, Cameron N; Freda, Philip J; Hennessy, Bryan M; Hockenberger, Kelsey; Jones, Jennifer K; King, Jessica E; Knob, Christopher R; Kraftmann, Karen J; Li, Linghui; Lupey, Lena N; Minniti, Carl J; Minton, Thomas F; Moran, Joseph V; Mudumbi, Krishna; Nordman, Elizabeth C; Puetz, William J; Robinson, Lauren M; Rose, Thomas J; Sweeney, Edward P; Timko, Ashley S; Paetkau, Don W; Eisler, Heather L; Aldrup, Megan E; Bodenberg, Jessica M; Cole, Mara G; Deranek, Kelly M; DeShetler, Megan; Dowd, Rose M; Eckardt, Alexandra K; Ehret, Sharon C; Fese, Jessica; Garrett, Amanda D; Kammrath, Anna; Kappes, Michelle L; Light, Morgan R; Meier, Anne C; O'Rouke, Allison; Perella, Mallory; Ramsey, Kimberley; Ramthun, Jennifer R; Reilly, Mary T; Robinett, Deirdre; Rossi, Nadine L; Schueler, Mary Grace; Shoemaker, Emma; Starkey, Kristin M; Vetor, Ashley; Vrable, Abby; Chandrasekaran, Vidya; Beck, Christopher; Hatfield, Kristen R; Herrick, Douglas A; Khoury, Christopher B; Lea, Charlotte; Louie, Christopher A; Lowell, Shannon M; Reynolds, Thomas J; Schibler, Jeanine; Scoma, Alexandra H; Smith-Gee, Maxwell T; Tuberty, Sarah; Smith, Christopher D; Lopilato, Jane E; Hauke, Jeanette; Roecklein-Canfield, Jennifer A; Corrielus, Maureen; Gilman, Hannah; Intriago, Stephanie; Maffa, Amanda; Rauf, Sabya A; Thistle, Katrina; Trieu, Melissa; Winters, Jenifer; Yang, Bib; Hauser, Charles R; Abusheikh, Tariq; Ashrawi, Yara; Benitez, Pedro; Boudreaux, Lauren R; Bourland, Megan; Chavez, Miranda; Cruz, Samantha; Elliott, GiNell; Farek, Jesse R; Flohr, Sarah; Flores, Amanda H; Friedrichs, Chelsey; Fusco, Zach; Goodwin, Zane; Helmreich, Eric; Kiley, John; Knepper, John Mark; Langner, Christine; Martinez, Megan; Mendoza, Carlos; Naik, Monal; Ochoa, Andrea; Ragland, Nicolas; Raimey, England; Rathore, Sunil; Reza, Evangelina; Sadovsky, Griffin; Seydoux, Marie-Isabelle B; Smith, Jonathan E; Unruh, Anna K; Velasquez, Vicente; Wolski, Matthew W; Gosser, Yuying; Govind, Shubha; Clarke-Medley, Nicole; Guadron, Leslie; Lau, Dawn; Lu, Alvin; Mazzeo, Cheryl; Meghdari, Mariam; Ng, Simon; Pamnani, Brad; Plante, Olivia; Shum, Yuki Kwan Wa; Song, Roy; Johnson, Diana E; Abdelnabi, Mai; Archambault, Alexi; Chamma, Norma; Gaur, Shailly; Hammett, Deborah; Kandahari, Adrese; Khayrullina, Guzal; Kumar, Sonali; Lawrence, Samantha; Madden, Nigel; Mandelbaum, Max; Milnthorp, Heather; Mohini, Shiv; Patel, Roshni; Peacock, Sarah J; Perling, Emily; Quintana, Amber; Rahimi, Michael; Ramirez, Kristen; Singhal, Rishi; Weeks, Corinne; Wong, Tiffany; Gillis, Aubree T; Moore, Zachary D; Savell, Christopher D; Watson, Reece; Mel, Stephanie F; Anilkumar, Arjun A; Bilinski, Paul; Castillo, Rostislav; Closser, Michael; Cruz, Nathalia M; Dai, Tiffany; Garbagnati, Giancarlo F; Horton, Lanor S; Kim, Dongyeon; Lau, Joyce H; Liu, James Z; Mach, Sandy D; Phan, Thu A; Ren, Yi; Stapleton, Kenneth E; Strelitz, Jean M; Sunjed, Ray; Stamm, Joyce; Anderson, Morgan C; Bonifield, Bethany Grace; Coomes, Daniel; Dillman, Adam; Durchholz, Elaine J; Fafara-Thompson, Antoinette E; Gross, Meleah J; Gygi, Amber M; Jackson, Lesley E; Johnson, Amy; Kocsisova, Zuzana; Manghelli, Joshua L; McNeil, Kylie; Murillo, Michael; Naylor, Kierstin L; Neely, Jessica; Ogawa, Emmy E; Rich, Ashley; Rogers, Anna; Spencer, J Devin; Stemler, Kristina M; Throm, Allison A; Van Camp, Matt; Weihbrecht, Katie; Wiles, T Aaron; Williams, Mallory A; Williams, Matthew; Zoll, Kyle; Bailey, Cheryl; Zhou, Leming; Balthaser, Darla M; Bashiri, Azita; Bower, Mindy E; Florian, Kayla A; Ghavam, Nazanin; Greiner-Sosanko, Elizabeth S; Karim, Helmet; Mullen, Victor W; Pelchen, Carly E; Yenerall, Paul M; Zhang, Jiayu; Rubin, Michael R; Arias-Mejias, Suzette M; Bermudez-Capo, Armando G; Bernal-Vega, Gabriela V; Colon-Vazquez, Mariela; Flores-Vazquez, Arelys; Gines-Rosario, Mariela; Llavona-Cartagena, Ivan G; Martinez-Rodriguez, Javier O; Ortiz-Fuentes, Lionel; Perez-Colomba, Eliezer O; Perez-Otero, Joseph; Rivera, Elisandra; Rodriguez-Giron, Luke J; Santiago-Sanabria, Arnaldo J; Senquiz-Gonzalez, Andrea M; delValle, Frank R Soto; Vargas-Franco, Dorianmarie; Velázquez-Soto, Karla I; Zambrana-Burgos, Joan D; Martinez-Cruzado, Juan Carlos; Asencio-Zayas, Lillyann; Babilonia-Figueroa, Kevin; Beauchamp-Pérez, Francis D; Belén-Rodríguez, Juliana; Bracero-Quiñones, Luciann; Burgos-Bula, Andrea P; Collado-Méndez, Xavier A; Colón-Cruz, Luis R; Correa-Muller, Ana I; Crooke-Rosado, Jonathan L; Cruz-García, José M; Defendini-Ávila, Marianna; Delgado-Peraza, Francheska M; Feliciano-Cancela, Alex J; Gónzalez-Pérez, Valerie M; Guiblet, Wilfried; Heredia-Negrón, Aldo; Hernández-Muñiz, Jennifer; Irizarry-González, Lourdes N; Laboy-Corales, Ángel L; Llaurador-Caraballo, Gabriela A; Marín-Maldonado, Frances; Marrero-Llerena, Ulises; Martell-Martínez, Héctor A; Martínez-Traverso, Idaliz M; Medina-Ortega, Kiara N; Méndez-Castellanos, Sonya G; Menéndez-Serrano, Krizia C; Morales-Caraballo, Carol I; Ortiz-DeChoudens, Saryleine; Ortiz-Ortiz, Patricia; Pagán-Torres, Hendrick; Pérez-Afanador, Diana; Quintana-Torres, Enid M; Ramírez-Aponte, Edwin G; Riascos-Cuero, Carolina; Rivera-Llovet, Michelle S; Rivera-Pagán, Ingrid T; Rivera-Vicéns, Ramón E; Robles-Juarbe, Fabiola; Rodríguez-Bonilla, Lorraine; Rodríguez-Echevarría, Brian O; Rodríguez-García, Priscila M; Rodríguez-Laboy, Abneris E; Rodríguez-Santiago, Susana; Rojas-Vargas, Michael L; Rubio-Marrero, Eva N; Santiago-Colón, Albeliz; Santiago-Ortiz, Jorge L; Santos-Ramos, Carlos E; Serrano-González, Joseline; Tamayo-Figueroa, Alina M; Tascón-Peñaranda, Edna P; Torres-Castillo, José L; Valentín-Feliciano, Nelson A; Valentín-Feliciano, Yashira M; Vargas-Barreto, Nadyan M; Vélez-Vázquez, Miguel; Vilanova-Vélez, Luis R; Zambrana-Echevarría, Cristina; MacKinnon, Christy; Chung, Hui-Min; Kay, Chris; Pinto, Anthony; Kopp, Olga R; Burkhardt, Joshua; Harward, Chris; Allen, Robert; Bhat, Pavan; Chang, Jimmy Hsiang-Chun; Chen, York; Chesley, Christopher; Cohn, Dara; DuPuis, David; Fasano, Michael; Fazzio, Nicholas; Gavinski, Katherine; Gebreyesus, Heran; Giarla, Thomas; Gostelow, Marcus; Greenstein, Rachel; Gunasinghe, Hashini; Hanson, Casey; Hay, Amanda; He, Tao Jian; Homa, Katie; Howe, Ruth; Howenstein, Jeff; Huang, Henry; Khatri, Aaditya; Kim, Young Lu; Knowles, Olivia; Kong, Sarah; Krock, Rebecca; Kroll, Matt; Kuhn, Julia; Kwong, Matthew; Lee, Brandon; Lee, Ryan; Levine, Kevin; Li, Yedda; Liu, Bo; Liu, Lucy; Liu, Max; Lousararian, Adam; Ma, Jimmy; Mallya, Allyson; Manchee, Charlie; Marcus, Joseph; McDaniel, Stephen; Miller, Michelle L; Molleston, Jerome M; Diez, Cristina Montero; Ng, Patrick; Ngai, Natalie; Nguyen, Hien; Nylander, Andrew; Pollack, Jason; Rastogi, Suchita; Reddy, Himabindu; Regenold, Nathaniel; Sarezky, Jon; Schultz, Michael; Shim, Jien; Skorupa, Tara; Smith, Kenneth; Spencer, Sarah J; Srikanth, Priya; Stancu, Gabriel; Stein, Andrew P; Strother, Marshall; Sudmeier, Lisa; Sun, Mengyang; Sundaram, Varun; Tazudeen, Noor; Tseng, Alan; Tzeng, Albert; Venkat, Rohit; Venkataram, Sandeep; Waldman, Leah; Wang, Tracy; Yang, Hao; Yu, Jack Y; Zheng, Yin; Preuss, Mary L; Garcia, Angelica; Juergens, Matt; Morris, Robert W; Nagengast, Alexis A; Azarewicz, Julie; Carr, Thomas J; Chichearo, Nicole; Colgan, Mike; Donegan, Megan; Gardner, Bob; Kolba, Nik; Krumm, Janice L; Lytle, Stacey; MacMillian, Laurell; Miller, Mary; Montgomery, Andrew; Moretti, Alysha; Offenbacker, Brittney; Polen, Mike; Toth, John; Woytanowski, John; Kadlec, Lisa; Crawford, Justin; Spratt, Mary L; Adams, Ashley L; Barnard, Brianna K; Cheramie, Martin N; Eime, Anne M; Golden, Kathryn L; Hawkins, Allyson P; Hill, Jessica E; Kampmeier, Jessica A; Kern, Cody D; Magnuson, Emily E; Miller, Ashley R; Morrow, Cody M; Peairs, Julia C; Pickett, Gentry L; Popelka, Sarah A; Scott, Alexis J; Teepe, Emily J; TerMeer, Katie A; Watchinski, Carmen A; Watson, Lucas A; Weber, Rachel E; Woodard, Kate A; Barnard, Daron C; Appiah, Isaac; Giddens, Michelle M; McNeil, Gerard P; Adebayo, Adeola; Bagaeva, Kate; Chinwong, Justina; Dol, Chrystel; George, Eunice; Haltaufderhyde, Kirk; Haye, Joanna; Kaur, Manpreet; Semon, Max; Serjanov, Dmitri; Toorie, Anika; Wilson, Christopher; Riddle, Nicole C; Buhler, Jeremy; Mardis, Elaine R; Elgin, Sarah CRThe Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.Item Open Access Functional annotation signatures of disease susceptibility loci improve SNP association analysis.(BMC Genomics, 2014-05-24) Iversen, ES; Lipton, G; Clyde, MA; Monteiro, ANABACKGROUND: Genetic association studies are conducted to discover genetic loci that contribute to an inherited trait, identify the variants behind these associations and ascertain their functional role in determining the phenotype. To date, functional annotations of the genetic variants have rarely played more than an indirect role in assessing evidence for association. Here, we demonstrate how these data can be systematically integrated into an association study's analysis plan. RESULTS: We developed a Bayesian statistical model for the prior probability of phenotype-genotype association that incorporates data from past association studies and publicly available functional annotation data regarding the susceptibility variants under study. The model takes the form of a binary regression of association status on a set of annotation variables whose coefficients were estimated through an analysis of associated SNPs in the GWAS Catalog (GC). The functional predictors examined included measures that have been demonstrated to correlate with the association status of SNPs in the GC and some whose utility in this regard is speculative: summaries of the UCSC Human Genome Browser ENCODE super-track data, dbSNP function class, sequence conservation summaries, proximity to genomic variants in the Database of Genomic Variants and known regulatory elements in the Open Regulatory Annotation database, PolyPhen-2 probabilities and RegulomeDB categories. Because we expected that only a fraction of the annotations would contribute to predicting association, we employed a penalized likelihood method to reduce the impact of non-informative predictors and evaluated the model's ability to predict GC SNPs not used to construct the model. We show that the functional data alone are predictive of a SNP's presence in the GC. Further, using data from a genome-wide study of ovarian cancer, we demonstrate that their use as prior data when testing for association is practical at the genome-wide scale and improves power to detect associations. CONCLUSIONS: We show how diverse functional annotations can be efficiently combined to create 'functional signatures' that predict the a priori odds of a variant's association to a trait and how these signatures can be integrated into a standard genome-wide-scale association analysis, resulting in improved power to detect truly associated variants.Item Open Access Sustained-input switches for transcription factors and microRNAs are central building blocks of eukaryotic gene circuits.(Genome Biol, 2013-08-23) Megraw, Molly; Mukherjee, Sayan; Ohler, UweWaRSwap is a randomization algorithm that for the first time provides a practical network motif discovery method for large multi-layer networks, for example those that include transcription factors, microRNAs, and non-regulatory protein coding genes. The algorithm is applicable to systems with tens of thousands of genes, while accounting for critical aspects of biological networks, including self-loops, large hubs, and target rearrangements. We validate WaRSwap on a newly inferred regulatory network from Arabidopsis thaliana, and compare outcomes on published Drosophila and human networks. Specifically, sustained input switches are among the few over-represented circuits across this diverse set of eukaryotes.Item Open Access Three crocodilian genomes reveal ancestral patterns of evolution among archosaurs.(Science, 2014-12-12) Green, Richard E; Braun, Edward L; Armstrong, Joel; Earl, Dent; Nguyen, Ngan; Hickey, Glenn; Vandewege, Michael W; St John, John A; Capella-Gutiérrez, Salvador; Castoe, Todd A; Kern, Colin; Fujita, Matthew K; Opazo, Juan C; Jurka, Jerzy; Kojima, Kenji K; Caballero, Juan; Hubley, Robert M; Smit, Arian F; Platt, Roy N; Lavoie, Christine A; Ramakodi, Meganathan P; Finger, John W; Suh, Alexander; Isberg, Sally R; Miles, Lee; Chong, Amanda Y; Jaratlerdsiri, Weerachai; Gongora, Jaime; Moran, Christopher; Iriarte, Andrés; McCormack, John; Burgess, Shane C; Edwards, Scott V; Lyons, Eric; Williams, Christina; Breen, Matthew; Howard, Jason T; Gresham, Cathy R; Peterson, Daniel G; Schmitz, Jürgen; Pollock, David D; Haussler, David; Triplett, Eric W; Zhang, Guojie; Irie, Naoki; Jarvis, Erich D; Brochu, Christopher A; Schmidt, Carl J; McCarthy, Fiona M; Faircloth, Brant C; Hoffmann, Federico G; Glenn, Travis C; Gabaldón, Toni; Paten, Benedict; Ray, David ATo provide context for the diversification of archosaurs--the group that includes crocodilians, dinosaurs, and birds--we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.