126 results on '"Haeussler, Maximilian"'
Search Results
102. Corrigendum: Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal
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Mateo, Juan L., primary, van den Berg, Debbie L.C., additional, Haeussler, Maximilian, additional, Drechsel, Daniela, additional, Gaber, Zachary B., additional, Castro, Diogo S., additional, Robson, Paul, additional, Lu, Q. Richard, additional, Crawford, Gregory E., additional, Flicek, Paul, additional, Ettwiller, Laurence, additional, Wittbrodt, Joachim, additional, Guillemot, François, additional, and Martynoga, Ben, additional
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- 2016
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103. Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona
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Gandhi, Shashank, primary, Haeussler, Maximilian, additional, Razy-Krajka, Florian, additional, Christiaen, Lionel, additional, and Stolfi, Alberto, additional
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- 2016
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104. The UCSC Genome Browser database: 2016 update
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Speir, Matthew L., primary, Zweig, Ann S., additional, Rosenbloom, Kate R., additional, Raney, Brian J., additional, Paten, Benedict, additional, Nejad, Parisa, additional, Lee, Brian T., additional, Learned, Katrina, additional, Karolchik, Donna, additional, Hinrichs, Angie S., additional, Heitner, Steve, additional, Harte, Rachel A., additional, Haeussler, Maximilian, additional, Guruvadoo, Luvina, additional, Fujita, Pauline A., additional, Eisenhart, Christopher, additional, Diekhans, Mark, additional, Clawson, Hiram, additional, Casper, Jonathan, additional, Barber, Galt P., additional, Haussler, David, additional, Kuhn, Robert M., additional, and Kent, W. James, additional
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- 2015
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105. Ebola: an analysis of immunity at the molecular level
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Ponomarenko, Julia, primary, Vaughan, Kerrie, additional, Paul, Sinu, additional, Peters, Bjoern, additional, Sette, Alessandro, additional, Haeussler, Maximilian, additional, and Maurer-Stroh, Sebastian, additional
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- 2015
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106. A dual origin of the pituitary primordium in the ascidian
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Kano, Shungo, Satou, Y., Deschet, K., Martin, P., Haeussler, Maximilian, Joly, Jean-Stephane, USC CNRS jeune équipe Développement, Evolution et Plasticité du Système Nerveux (DEPSN), Institut National de la Recherche Agronomique (INRA), Society for Integrative and Comparative Biology (SICB). USA., and ProdInra, Migration
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,embryonic structures ,[INFO]Computer Science [cs] ,[INFO] Computer Science [cs] - Abstract
The pituitary is an essential endocrine organ in the vertebrates. While the urochordate possesses no distinct pituitary organ, it has been long proposed that the ascidian neural complex (NC) composes homologous organs to the brain and the pituitary. Recent molecular data suggests that the ciliated funnel (CF), one of the NC components, is the most probable candidate as several placodal genes including CiPitx are expressed at the ectodermal stomodaeum and the CF, respectively, in embryonic and the adult stages (Boorman and Shimeld, 2002; Christiaen et al., 2002). To reinforce this hypothesis with insights from the developmental process, we conducted lineage analyses mainly using a photo-convertible fluorescent protein Kaede driven with promoters recapitulating endogenous expressions of CiPitx and CiNut (the neural tube marker). We validated that a part of the ectodermal stomodeaum invaginates, separates from the major part and gives rise to the distal tip of the CF. Furthermore, we revealed that the proximal domain of the CF, which is adjacent to the distal tip, is derived from the neuroectodermal "dorsal duct". Thus, the ascidian CF has a dual origin and its organogenesis resembles the vertebrate pituitary. We then investigated whether the ectodermal CF expresses genes relevant to an endocrine activity like the vertebrate pituitary. However, we could not confirm it. It is likely that a pituitary primordium is present in the ascidian, but that the endocrine activity of the pituitary is a vertebrate innovation presumably with evolutions of adenohypophyseal transcription factors which terminally differentiate hormone-secreting cells.
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- 2010
107. The UCSC Genome Browser database: 2015 update
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Rosenbloom, Kate R., primary, Armstrong, Joel, additional, Barber, Galt P., additional, Casper, Jonathan, additional, Clawson, Hiram, additional, Diekhans, Mark, additional, Dreszer, Timothy R., additional, Fujita, Pauline A., additional, Guruvadoo, Luvina, additional, Haeussler, Maximilian, additional, Harte, Rachel A., additional, Heitner, Steve, additional, Hickey, Glenn, additional, Hinrichs, Angie S., additional, Hubley, Robert, additional, Karolchik, Donna, additional, Learned, Katrina, additional, Lee, Brian T., additional, Li, Chin H., additional, Miga, Karen H., additional, Nguyen, Ngan, additional, Paten, Benedict, additional, Raney, Brian J., additional, Smit, Arian F. A., additional, Speir, Matthew L., additional, Zweig, Ann S., additional, Haussler, David, additional, Kuhn, Robert M., additional, and Kent, W. James, additional
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- 2014
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108. Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal
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Mateo, Juan L., primary, van den Berg, Debbie L.C., additional, Haeussler, Maximilian, additional, Drechsel, Daniela, additional, Gaber, Zachary B., additional, Castro, Diogo S., additional, Robson, Paul, additional, Lu, Q. Richard, additional, Crawford, Gregory E., additional, Flicek, Paul, additional, Ettwiller, Laurence, additional, Wittbrodt, Joachim, additional, Guillemot, François, additional, and Martynoga, Ben, additional
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- 2014
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109. The UCSC Ebola Genome Portal
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Haeussler, Maximilian, primary, Karolchik, Donna, additional, Clawson, Hiram, additional, Raney, Brian J, additional, Rosenbloom, Kate R., additional, Fujita, Pauline A., additional, Hinrichs, Angie S., additional, Speir, Matthew L, additional, Eisenhart, Chris, additional, Zweig, Ann S., additional, Haussler, David, additional, and Kent, W. James, additional
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- 2014
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110. The UCSC Genome Browser database: 2014 update
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Karolchik, Donna, primary, Barber, Galt P., additional, Casper, Jonathan, additional, Clawson, Hiram, additional, Cline, Melissa S., additional, Diekhans, Mark, additional, Dreszer, Timothy R., additional, Fujita, Pauline A., additional, Guruvadoo, Luvina, additional, Haeussler, Maximilian, additional, Harte, Rachel A., additional, Heitner, Steve, additional, Hinrichs, Angie S., additional, Learned, Katrina, additional, Lee, Brian T., additional, Li, Chin H., additional, Raney, Brian J., additional, Rhead, Brooke, additional, Rosenbloom, Kate R., additional, Sloan, Cricket A., additional, Speir, Matthew L., additional, Zweig, Ann S., additional, Haussler, David, additional, Kuhn, Robert M., additional, and Kent, W. James, additional
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- 2013
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111. Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics
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Barbeira, Alvaro N., Dickinson, Scott P., Bonazzola, Rodrigo, Zheng, Jiamao, Wheeler, Heather E., Torres, Jason M., Torstenson, Eric S., Shah, Kaanan P., Garcia, Tzintzuni, Edwards, Todd L., Stahl, Eli A., Huckins, Laura M., Aguet, François, Ardlie, Kristin G., Cummings, Beryl B., Gelfand, Ellen T., Getz, Gad, Hadley, Kane, Handsaker, Robert E., Huang, Katherine H., Kashin, Seva, Karczewski, Konrad J., Lek, Monkol, Li, Xiao, MacArthur, Daniel G., Nedzel, Jared L., Nguyen, Duyen T., Noble, Michael S., Segrè, Ayellet V., Trowbridge, Casandra A., Tukiainen, Taru, Abell, Nathan S., Balliu, Brunilda, Barshir, Ruth, Basha, Omer, Battle, Alexis, Bogu, Gireesh K., Brown, Andrew, Brown, Christopher D., Castel, Stephane E., Chen, Lin S., Chiang, Colby, Conrad, Donald F., Damani, Farhan N., Davis, Joe R., Delaneau, Olivier, Dermitzakis, Emmanouil T., Engelhardt, Barbara E., Eskin, Eleazar, Ferreira, Pedro G., Frésard, Laure, Gamazon, Eric R., Garrido-Martín, Diego, Gewirtz, Ariel D. H., Gliner, Genna, Gloudemans, Michael J., Guigo, Roderic, Hall, Ira M., Han, Buhm, He, Yuan, Hormozdiari, Farhad, Howald, Cedric, Jo, Brian, Kang, Eun Yong, Kim, Yungil, Kim-Hellmuth, Sarah, Lappalainen, Tuuli, Li, Gen, Li, Xin, Liu, Boxiang, Mangul, Serghei, McCarthy, Mark I., McDowell, Ian C., Mohammadi, Pejman, Monlong, Jean, Montgomery, Stephen B., Muñoz-Aguirre, Manuel, Ndungu, Anne W., Nobel, Andrew B., Oliva, Meritxell, Ongen, Halit, Palowitch, John J., Panousis, Nikolaos, Papasaikas, Panagiotis, Park, YoSon, Parsana, Princy, Payne, Anthony J., Peterson, Christine B., Quan, Jie, Reverter, Ferran, Sabatti, Chiara, Saha, Ashis, Sammeth, Michael, Scott, Alexandra J., Shabalin, Andrey A., Sodaei, Reza, Stephens, Matthew, Stranger, Barbara E., Strober, Benjamin J., Sul, Jae Hoon, Tsang, Emily K., Urbut, Sarah, van de Bunt, Martijn, Wang, Gao, Wen, Xiaoquan, Wright, Fred A., Xi, Hualin S., Yeger-Lotem, Esti, Zappala, Zachary, Zaugg, Judith B., Zhou, Yi-Hui, Akey, Joshua M., Bates, Daniel, Chan, Joanne, Claussnitzer, Melina, Demanelis, Kathryn, Diegel, Morgan, Doherty, Jennifer A., Feinberg, Andrew P., Fernando, Marian S., Halow, Jessica, Hansen, Kasper D., Haugen, Eric, Hickey, Peter F., Hou, Lei, Jasmine, Farzana, Jian, Ruiqi, Jiang, Lihua, Johnson, Audra, Kaul, Rajinder, Kellis, Manolis, Kibriya, Muhammad G., Lee, Kristen, Li, Jin Billy, Li, Qin, Lin, Jessica, Lin, Shin, Linder, Sandra, Linke, Caroline, Liu, Yaping, Maurano, Matthew T., Molinie, Benoit, Nelson, Jemma, Neri, Fidencio J., Park, Yongjin, Pierce, Brandon L., Rinaldi, Nicola J., Rizzardi, Lindsay F., Sandstrom, Richard, Skol, Andrew, Smith, Kevin S., Snyder, Michael P., Stamatoyannopoulos, John, Tang, Hua, Wang, Li, Wang, Meng, Van Wittenberghe, Nicholas, Wu, Fan, Zhang, Rui, Nierras, Concepcion R., Branton, Philip A., Carithers, Latarsha J., Guan, Ping, Moore, Helen M., Rao, Abhi, Vaught, Jimmie B., Gould, Sarah E., Lockart, Nicole C., Martin, Casey, Struewing, Jeffery P., Volpi, Simona, Addington, Anjene M., Koester, Susan E., Little, A. Roger, Brigham, Lori E., Hasz, Richard, Hunter, Marcus, Johns, Christopher, Johnson, Mark, Kopen, Gene, Leinweber, William F., Lonsdale, John T., McDonald, Alisa, Mestichelli, Bernadette, Myer, Kevin, Roe, Brian, Salvatore, Michael, Shad, Saboor, Thomas, Jeffrey A., Walters, Gary, Washington, Michael, Wheeler, Joseph, Bridge, Jason, Foster, Barbara A., Gillard, Bryan M., Karasik, Ellen, Kumar, Rachna, Miklos, Mark, Moser, Michael T., Jewell, Scott D., Montroy, Robert G., Rohrer, Daniel C., Valley, Dana R., Davis, David A., Mash, Deborah C., Undale, Anita H., Smith, Anna M., Tabor, David E., Roche, Nancy V., McLean, Jeffrey A., Vatanian, Negin, Robinson, Karna L., Sobin, Leslie, Barcus, Mary E., Valentino, Kimberly M., Qi, Liqun, Hunter, Steven, Hariharan, Pushpa, Singh, Shilpi, Um, Ki Sung, Matose, Takunda, Tomaszewski, Maria M., Barker, Laura K., Mosavel, Maghboeba, Siminoff, Laura A., Traino, Heather M., Flicek, Paul, Juettemann, Thomas, Ruffier, Magali, Sheppard, Dan, Taylor, Kieron, Trevanion, Stephen J., Zerbino, Daniel R., Craft, Brian, Goldman, Mary, Haeussler, Maximilian, Kent, W. James, Lee, Christopher M., Paten, Benedict, Rosenbloom, Kate R., Vivian, John, Zhu, Jingchun, Nicolae, Dan L., Cox, Nancy J., and Im, Hae Kyung
- Abstract
Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease genes are enriched among significant associations for related traits, suggesting that smaller alterations of these genes may cause a spectrum of milder phenotypes.
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- 2018
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112. The UCSC Genome Browser database: extensions and updates 2013
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Meyer, Laurence R., primary, Zweig, Ann S., additional, Hinrichs, Angie S., additional, Karolchik, Donna, additional, Kuhn, Robert M., additional, Wong, Matthew, additional, Sloan, Cricket A., additional, Rosenbloom, Kate R., additional, Roe, Greg, additional, Rhead, Brooke, additional, Raney, Brian J., additional, Pohl, Andy, additional, Malladi, Venkat S., additional, Li, Chin H., additional, Lee, Brian T., additional, Learned, Katrina, additional, Kirkup, Vanessa, additional, Hsu, Fan, additional, Heitner, Steve, additional, Harte, Rachel A., additional, Haeussler, Maximilian, additional, Guruvadoo, Luvina, additional, Goldman, Mary, additional, Giardine, Belinda M., additional, Fujita, Pauline A., additional, Dreszer, Timothy R., additional, Diekhans, Mark, additional, Cline, Melissa S., additional, Clawson, Hiram, additional, Barber, Galt P., additional, Haussler, David, additional, and Kent, W. James, additional
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- 2012
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113. Initial deployment of the cardiogenic gene regulatory network in the basal chordate, Ciona intestinalis
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Woznica, Arielle, primary, Haeussler, Maximilian, additional, Starobinska, Ella, additional, Jemmett, Jessica, additional, Li, Younan, additional, Mount, David, additional, and Davidson, Brad, additional
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- 2012
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114. pubmed2ensembl: A Resource for Mining the Biological Literature on Genes
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Baran, Joachim, primary, Gerner, Martin, additional, Haeussler, Maximilian, additional, Nenadic, Goran, additional, and Bergman, Casey M., additional
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- 2011
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115. Annotating genes and genomes with DNA sequences extracted from biomedical articles
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Haeussler, Maximilian, primary, Gerner, Martin, additional, and Bergman, Casey M., additional
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- 2011
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116. When needles look like hay: How to find tissue-specific enhancers in model organism genomes
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Haeussler, Maximilian, primary and Joly, Jean-Stéphane, additional
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- 2011
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117. A cis-Regulatory Signature for Chordate Anterior Neuroectodermal Genes
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Haeussler, Maximilian, primary, Jaszczyszyn, Yan, additional, Christiaen, Lionel, additional, and Joly, Jean-Stéphane, additional
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- 2010
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118. Text-mining assisted regulatory annotation
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Aerts, Stein, primary, Haeussler, Maximilian, additional, van Vooren, Steven, additional, Griffith, Obi L, additional, Hulpiau, Paco, additional, Jones, Steven JM, additional, Montgomery, Stephen B, additional, Bergman, Casey M, additional, and Consortium, The Open Regulatory Annotation, additional
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- 2008
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119. Comparison of the expression of medaka (Oryzias latipes) pitx genes with other vertebrates shows high conservation and a case of functional shuffling in the pituitary
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Jaszczyszyn, Yan, primary, Haeussler, Maximilian, additional, Heuzé, Aurélie, additional, Debiais-Thibaud, Mélanie, additional, Casane, Didier, additional, Bourrat, Franck, additional, and Joly, Jean-Stéphane, additional
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- 2007
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120. Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal
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Mateo, Juan L., van den Berg, Debbie L.C., Haeussler, Maximilian, Drechsel, Daniela, Gaber, Zachary B., Castro, Diogo S., Robson, Paul, Crawford, Gregory E., Flicek, Paul, Ettwiller, Laurence, Wittbrodt, Joachim, Guillemot, Francois, and Martynoga, Ben
- Abstract
The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence.
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- 2015
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121. Registered access: authorizing data access
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Dyke, Stephanie O.M., Linden, Mikael, Lappalainen, Ilkka, De Argila, Jordi R., Carey, Knox, Lloyd, David, Spalding, J.D., Cabili, Moran N., Kerry, Giselle, Foreman, Julia, Cutts, Tim, Shabani, Mahsa, Rodriguez, Laura L., Haeussler, Maximilian, Walsh, Brian, Jiang, Xiaoqian, Wang, Shuang, Perrett, Daniel, Boughtwood, Tiffany, Matern, Andreas, Brookes, Anthony J., Cupak, Miro, Fiume, Marc, Pandya, Ravi, Tulchinsky, Ilia, Scollen, Serena, Törnroos, Juha, Das, Samir, Evans, Alan C., Malin, Bradley A., Beck, Stephan, Brenner, Steven E., Nyrönen, Tommi, Blomberg, Niklas, Firth, Helen V., Hurles, Matthew, Philippakis, Anthony A., Rätsch, Gunnar, Brudno, Michael, Boycott, Kym M., Rehm, Heidi L., Baudis, Michael, Sherry, Stephen T., Kato, Kazuto, Knoppers, Bartha M., Baker, Dixie, and Flicek, Paul
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3. Good health - Abstract
The Global Alliance for Genomics and Health (GA4GH) proposes a data access policy model—“registered access”—to increase and improve access to data requiring an agreement to basic terms and conditions, such as the use of DNA sequence and health data in research. A registered access policy would enable a range of categories of users to gain access, starting with researchers and clinical care professionals. It would also facilitate general use and reuse of data but within the bounds of consent restrictions and other ethical obligations. In piloting registered access with the Scientific Demonstration data sharing projects of GA4GH, we provide additional ethics, policy and technical guidance to facilitate the implementation of this access model in an international setting., European Journal of Human Genetics, 26 (12), ISSN:1476-5438, ISSN:1018-4813
122. A Panoramic View of Cell Population Dynamics in Mammalian Aging.
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Zhang Z, Schaefer C, Jiang W, Lu Z, Lee J, Sziraki A, Abdulraouf A, Wick B, Haeussler M, Li Z, Molla G, Satija R, Zhou W, and Cao J
- Abstract
To elucidate the aging-associated cellular population dynamics throughout the body, here we present PanSci, a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissue samples, encompassing a range of organs across different life stages, sexes, and genotypes. This comprehensive dataset allowed us to identify more than 3,000 unique cellular states and catalog over 200 distinct aging-associated cell populations experiencing significant depletion or expansion. Our panoramic analysis uncovered temporally structured, organ- and lineage-specific shifts of cellular dynamics during lifespan progression. Moreover, we investigated aging-associated alterations in immune cell populations, revealing both widespread shifts and organ-specific changes. We further explored the regulatory roles of the immune system on aging and pinpointed specific age-related cell population expansions that are lymphocyte-dependent. The breadth and depth of our 'cell-omics' methodology not only enhance our comprehension of cellular aging but also lay the groundwork for exploring the complex regulatory networks among varied cell types in the context of aging and aging-associated diseases., Competing Interests: Competing interests: In the past 3 years, R.S. has received compensation from Bristol-Myers Squibb, ImmunAI, Resolve Biosciences, Nanostring, 10x Genomics, Neptune Bio, and the NYC Pandemic Response Lab. R.S. is a co-founder and equity holder of Neptune Bio.
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- 2024
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123. Single cell analysis of dup15q syndrome reveals developmental and postnatal molecular changes in autism.
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Perez Y, Velmeshev D, Wang L, White M, Siebert C, Baltazar J, Dutton NG, Wang S, Haeussler M, Chamberlain S, and Kriegstein A
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Duplication 15q (dup15q) syndrome is the most common genetic cause of autism spectrum disorder (ASD). Due to a higher genetic and phenotypic homogeneity compared to idiopathic autism, dup15q syndrome provides a well-defined setting to investigate ASD mechanisms. Previous bulk gene expression studies identified shared molecular changes in ASD. However, how cell type specific changes compare across different autism subtypes and how they change during development is largely unknown. In this study, we used single cell and single nucleus mRNA sequencing of dup15q cortical organoids from patient iPSCs, as well as post-mortem patient brain samples. We find cell-type specific dysregulated programs that underlie dup15q pathogenesis, which we validate by spatial resolved transcriptomics using brain tissue samples. We find degraded identity and vulnerability of deep-layer neurons in fetal stage organoids and highlight increased molecular burden of postmortem upper-layer neurons implicated in synaptic signaling, a finding shared between idiopathic ASD and dup15q syndrome. Gene co-expression network analysis of organoid and postmortem excitatory neurons uncovers modules enriched with autism risk genes. Organoid developmental modules were involved in transcription regulation via chromatin remodeling, while postmortem modules were associated with synaptic transmission and plasticity. The findings reveal a shifting landscape of ASD cellular vulnerability during brain development.
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- 2023
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124. A Meta-Atlas of the Developing Human Cortex Identifies Modules Driving Cell Subtype Specification.
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Nano PR, Fazzari E, Azizad D, Nguyen CV, Wang S, Kan RL, Wick B, Haeussler M, and Bhaduri A
- Abstract
Human brain development requires the generation of hundreds of diverse cell types, a process targeted by recent single-cell transcriptomic profiling efforts. Through a meta-analysis of seven of these published datasets, we have generated 225 meta-modules - gene co-expression networks that can describe mechanisms underlying cortical development. Several meta-modules have potential roles in both establishing and refining cortical cell type identities, and we validated their spatiotemporal expression in primary human cortical tissues. These include meta-module 20, associated with FEZF2+ deep layer neurons. Half of meta-module 20 genes are putative FEZF2 targets, including TSHZ3, a transcription factor associated with neurodevelopmental disorders. Human cortical organoid experiments validated that both factors are necessary for deep layer neuron specification. Importantly, subtle manipulations of these factors drive slight changes in meta-module activity that cascade into strong differences in cell fate - demonstrating how of our meta-atlas can engender further mechanistic analyses of cortical fate specification.
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- 2023
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125. GenArk: Towards a million UCSC Genome Browsers.
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Clawson H, Lee BT, Raney BJ, Barber GP, Casper J, Diekhans M, Fischer C, Gonzalez JN, Hinrichs AS, Lee CM, Nassar LR, Perez G, Wick B, Schmelter D, Speir ML, Armstrong J, Zweig AS, Kuhn RM, Kirilenko BM, Hiller M, Haussler D, Kent WJ, and Haeussler M
- Abstract
Interactive graphical genome browsers are essential tools for biologists working with DNA sequences. Although tens of thousands of new genome assemblies have become available over the last decade, accessibility is limited by the work involved in manually creating browsers and curating annotations. The results can push the limits of data storage infrastructure. To facilitate managing this increasing number of genome assemblies, we created the Genome Archive (GenArk) collection of UCSC Genome Browsers from assemblies hosted at NCBI(1). Built on our established assembly hub system, this collection enables fast, on-demand visualization of chromosome regions without requiring a database server. Available annotations include gene models, some mapped through whole-genome alignments, repeat masks, GC content, and others. We also modified our popular BLAT(2) aligner and in-silico PCR to support a large number of genomes using limited RAM. Users can upload additional annotations themselves via track hubs(3) and custom tracks. We can import more annotations in bulk from third-party resources, demonstrated here with TOGA(4) gene models. 2,430 GenArk assemblies are listed at https://hgdownload.soe.ucsc.edu/hubs/ and can be found by searching on the main UCSC gateway page. We will continue to add human high-quality assemblies and for other organisms, we are looking forward to receiving requests from the research community for ever more browsers and whole-genome alignments via http://genome.ucsc.edu/assemblyRequest.html.
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- 2023
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126. A new SARS-CoV-2 lineage that shares mutations with known Variants of Concern is rejected by automated sequence repository quality control.
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Thornlow B, Hinrichs AS, Jain M, Dhillon N, La S, Kapp JD, Anigbogu I, Cassatt-Johnstone M, McBroome J, Haeussler M, Turakhia Y, Chang T, Olsen HE, Sanford J, Stone M, Vaske O, Bjork I, Akeson M, Shapiro B, Haussler D, Kilpatrick AM, and Corbett-Detig R
- Abstract
We report a SARS-CoV-2 lineage that shares N501Y, P681H, and other mutations with known variants of concern, such as B.1.1.7. This lineage, which we refer to as B.1.x (COG-UK sometimes references similar samples as B.1.324.1), is present in at least 20 states across the USA and in at least six countries. However, a large deletion causes the sequence to be automatically rejected from repositories, suggesting that the frequency of this new lineage is underestimated using public data. Recent dynamics based on 339 samples obtained in Santa Cruz County, CA, USA suggest that B.1.x may be increasing in frequency at a rate similar to that of B.1.1.7 in Southern California. At present the functional differences between this variant B.1.x and other circulating SARS-CoV-2 variants are unknown, and further studies on secondary attack rates, viral loads, immune evasion and/or disease severity are needed to determine if it poses a public health concern. Nonetheless, given what is known from well-studied circulating variants of concern, it seems unlikely that the lineage could pose larger concerns for human health than many already globally distributed lineages. Our work highlights a need for rapid turnaround time from sequence generation to submission and improved sequence quality control that removes submission bias. We identify promising paths toward this goal.
- Published
- 2021
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