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1. Maize genomes to fields (G2F): 2014–2017 field seasons: genotype, phenotype, climatic, soil, and inbred ear image datasets

Author

Bridget A. McFarland, Naser AlKhalifah, Martin Bohn, Jessica Bubert, Edward S. Buckler, Ignacio Ciampitti, Jode Edwards, David Ertl, Joseph L. Gage, Celeste M. Falcon, Sherry Flint-Garcia, Michael A. Gore, Christopher Graham, Candice N. Hirsch, James B. Holland, Elizabeth Hood, David Hooker, Diego Jarquin, Shawn M. Kaeppler, Joseph Knoll, Greg Kruger, Nick Lauter, Elizabeth C. Lee, Dayane C. Lima, Aaron Lorenz, Jonathan P. Lynch, John McKay, Nathan D. Miller, Stephen P. Moose, Seth C. Murray, Rebecca Nelson, Christina Poudyal, Torbert Rocheford, Oscar Rodriguez, Maria Cinta Romay, James C. Schnable, Patrick S. Schnable, Brian Scully, Rajandeep Sekhon, Kevin Silverstein, Maninder Singh, Margaret Smith, Edgar P. Spalding, Nathan Springer, Kurt Thelen, Peter Thomison, Mitchell Tuinstra, Jason Wallace, Ramona Walls, David Wills, Randall J. Wisser, Wenwei Xu, Cheng-Ting Yeh, and Natalia de Leon

Subjects
Maize, Genome, Genotype, GBS, G × E, Hybrid, Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract

Abstract Objectives Advanced tools and resources are needed to efficiently and sustainably produce food for an increasing world population in the context of variable environmental conditions. The maize genomes to fields (G2F) initiative is a multi-institutional initiative effort that seeks to approach this challenge by developing a flexible and distributed infrastructure addressing emerging problems. G2F has generated large-scale phenotypic, genotypic, and environmental datasets using publicly available inbred lines and hybrids evaluated through a network of collaborators that are part of the G2F’s genotype-by-environment (G × E) project. This report covers the public release of datasets for 2014–2017. Data description Datasets include inbred genotypic information; phenotypic, climatic, and soil measurements and metadata information for each testing location across years. For a subset of inbreds in 2014 and 2015, yield component phenotypes were quantified by image analysis. Data released are accompanied by README descriptions. For genotypic and phenotypic data, both raw data and a version without outliers are reported. For climatic data, a version calibrated to the nearest airport weather station and a version without outliers are reported. The 2014 and 2015 datasets are updated versions from the previously released files [1] while 2016 and 2017 datasets are newly available to the public.

Published
2020
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2. The Ontologies Community of Practice: A CGIAR Initiative for Big Data in Agrifood Systems

Author

Elizabeth Arnaud, Marie-Angélique Laporte, Soonho Kim, Céline Aubert, Sabina Leonelli, Berta Miro, Laurel Cooper, Pankaj Jaiswal, Gideon Kruseman, Rosemary Shrestha, Pier Luigi Buttigieg, Christopher J. Mungall, Julian Pietragalla, Afolabi Agbona, Jacqueline Muliro, Jeffrey Detras, Vilma Hualla, Abhishek Rathore, Roma Rani Das, Ibnou Dieng, Guillaume Bauchet, Naama Menda, Cyril Pommier, Felix Shaw, David Lyon, Leroy Mwanzia, Henry Juarez, Enrico Bonaiuti, Brian Chiputwa, Olatunbosun Obileye, Sandrine Auzoux, Esther Dzalé Yeumo, Lukas A. Mueller, Kevin Silverstein, Alexandra Lafargue, Erick Antezana, Medha Devare, and Brian King

Subjects
ontologies, agriculture, agrifood systems, Big Data, FAIR data, data annotation, Computer software, QA76.75-76.765
Abstract

Summary: Heterogeneous and multidisciplinary data generated by research on sustainable global agriculture and agrifood systems requires quality data labeling or annotation in order to be interoperable. As recommended by the FAIR principles, data, labels, and metadata must use controlled vocabularies and ontologies that are popular in the knowledge domain and commonly used by the community. Despite the existence of robust ontologies in the Life Sciences, there is currently no comprehensive full set of ontologies recommended for data annotation across agricultural research disciplines. In this paper, we discuss the added value of the Ontologies Community of Practice (CoP) of the CGIAR Platform for Big Data in Agriculture for harnessing relevant expertise in ontology development and identifying innovative solutions that support quality data annotation. The Ontologies CoP stimulates knowledge sharing among stakeholders, such as researchers, data managers, domain experts, experts in ontology design, and platform development teams. The Bigger Picture: Digital technology use in agriculture and agrifood systems research accelerates the production of multidisciplinary data, which spans genetics, environment, agroecology, biology, and socio-economics. Quality labeling of data secures its online findability, reusability, interoperability, and reliable interpretation, through controlled vocabularies organized into meaningful and computer-readable knowledge domains called ontologies. There is currently no full set of recommended ontologies for agricultural research, so data scientists, data managers, and database developers struggle to find validated terminology. The Ontologies Community of Practice of the CGIAR Platform for Big Data in Agriculture harnesses international expertise in knowledge representation and ontology development to produce missing ontologies, identifies best practices, and guides data labeling by teams managing multidisciplinary information platforms to release the FAIR data underpinning the evidence of research impact.

Published
2020
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3. Next generation sequencing for clinical diagnostics: Five year experience of an academic laboratory

Author

Paige Hartman, Kenneth Beckman, Kevin Silverstein, Sophia Yohe, Matthew Schomaker, Christine Henzler, Getiria Onsongo, Ham Ching Lam, Sarah Munro, Jerry Daniel, Bradley Billstein, Archana Deshpande, Adam Hauge, Pawel Mroz, Whiwon Lee, Jennifer Holle, Katie Wiens, Kylene Karnuth, Teresa Kemmer, Michaela Leary, Stephen Michel, Laurie Pohlman, Venugopal Thayanithy, Andrew Nelson, Matthew Bower, and Bharat Thyagarajan

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Clinical laboratories have adopted next generation sequencing (NGS) as a gold standard for the diagnosis of hereditary disorders because of its analytic accuracy, high throughput, and potential for cost-effectiveness. We describe the implementation of a single broad-based NGS sequencing assay to meet the genetic testing needs at the University of Minnesota. A single hybrid capture library preparation was used for each test ordered, data was informatically blinded to clinically-ordered genes, and identified variants were reviewed and classified by genetic counselors and molecular pathologists. We performed 2509 sequencing tests from August 2012 till December 2017. The diagnostic yield has remained steady at 25%, but the number of variants of uncertain significance (VUS) included in a patient report decreased over time with 50% of the patient reports including at least one VUS in 2012 and only 22% of the patient reports reporting a VUS in 2017 (p = .002). Among the various clinical specialties, the diagnostic yield was highest in dermatology (60% diagnostic yield) and ophthalmology (42% diagnostic yield) while the diagnostic yield was lowest in gastrointestinal diseases and pulmonary diseases (10% detection yield in both specialties). Deletion/duplication analysis was also implemented in a subset of panels ordered, with 9% of samples having a diagnostic finding using the deletion/duplication analysis. We have demonstrated the feasibility of this broad-based NGS platform to meet the needs of our academic institution by aggregating a sufficient sample volume from many individually rare tests and providing a flexible ordering for custom, patient-specific panels. Keywords: Next generation sequencing, Molecular diagnostics, Panel testing, Diagnostic yield, Variants of uncertain significance, Copy number variation

Published
2019
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4. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

Author

Leslie A. Lange, Youna Hu, He Zhang, Chenyi Xue, Ellen M. Schmidt, Zheng-Zheng Tang, Chris Bizon, Ethan M. Lange, Joshua D. Smith, Emily H. Turner, Goo Jun, Hyun Min Kang, Gina Peloso, Paul Auer, Kuo-ping Li, Jason Flannick, Ji Zhang, Christian Fuchsberger, Kyle Gaulton, Cecilia Lindgren, Adam Locke, Alisa Manning, Xueling Sim, Manuel A. Rivas, Oddgeir L. Holmen, Omri Gottesman, Yingchang Lu, Douglas Ruderfer, Eli A. Stahl, Qing Duan, Yun Li, Peter Durda, Shuo Jiao, Aaron Isaacs, Albert Hofman, Joshua C. Bis, Adolfo Correa, Michael E. Griswold, Johanna Jakobsdottir, Albert V. Smith, Pamela J. Schreiner, Mary F. Feitosa, Qunyuan Zhang, Jennifer E. Huffman, Jacy Crosby, Christina L. Wassel, Ron Do, Nora Franceschini, Lisa W. Martin, Jennifer G. Robinson, Themistocles L. Assimes, David R. Crosslin, Elisabeth A. Rosenthal, Michael Tsai, Mark J. Rieder, Deborah N. Farlow, Aaron R. Folsom, Thomas Lumley, Ervin R. Fox, Christopher S. Carlson, Ulrike Peters, Rebecca D. Jackson, Cornelia M. van Duijn, André G. Uitterlinden, Daniel Levy, Jerome I. Rotter, Herman A. Taylor, Vilmundur Gudnason, David S. Siscovick, Myriam Fornage, Ingrid B. Borecki, Caroline Hayward, Igor Rudan, Y. Eugene Chen, Erwin P. Bottinger, Ruth J.F. Loos, Pål Sætrom, Kristian Hveem, Michael Boehnke, Leif Groop, Mark McCarthy, Thomas Meitinger, Christie M. Ballantyne, Stacey B. Gabriel, Christopher J. O’Donnell, Wendy S. Post, Kari E. North, Alexander P. Reiner, Eric Boerwinkle, Bruce M. Psaty, David Altshuler, Sekar Kathiresan, Dan-Yu Lin, Gail P. Jarvik, L. Adrienne Cupples, Charles Kooperberg, James G. Wilson, Deborah A. Nickerson, Goncalo R. Abecasis, Stephen S. Rich, Russell P. Tracy, Cristen J. Willer, David M. Altshuler, Gonçalo R. Abecasis, Hooman Allayee, Sharon Cresci, Mark J. Daly, Paul I.W. de Bakker, Mark A. DePristo, Peter Donnelly, Tim Fennell, Kiran Garimella, Stanley L. Hazen, Daniel M. Jordan, Adam Kiezun, Guillaume Lettre, Bingshan Li, Mingyao Li, Christopher H. Newton-Cheh, Sandosh Padmanabhan, Sara Pulit, Daniel J. Rader, David Reich, Muredach P. Reilly, Steve Schwartz, Laura Scott, John A. Spertus, Nathaniel O. Stitziel, Nina Stoletzki, Shamil R. Sunyaev, Benjamin F. Voight, Ermeg Akylbekova, Larry D. Atwood, Maja Barbalic, R. Graham Barr, Emelia J. Benjamin, Joshua Bis, Donald W. Bowden, Jennifer Brody, Matthew Budoff, Greg Burke, Sarah Buxbaum, Jeff Carr, Donna T. Chen, Ida Y. Chen, Wei-Min Chen, Pat Concannon, Ralph D’Agostino, Anita L. DeStefano, Albert Dreisbach, Josée Dupuis, J. Peter Durda, Jaclyn Ellis, Caroline S. Fox, Ervin Fox, Vincent Funari, Santhi K. Ganesh, Julius Gardin, David Goff, Ora Gordon, Wayne Grody, Myron Gross, Xiuqing Guo, Ira M. Hall, Nancy L. Heard-Costa, Susan R. Heckbert, Nicholas Heintz, David M. Herrington, DeMarc Hickson, Jie Huang, Shih-Jen Hwang, David R. Jacobs, Nancy S. Jenny, Andrew D. Johnson, Craig W. Johnson, Steven Kawut, Richard Kronmal, Raluca Kurz, Martin G. Larson, Mark Lawson, Cora E. Lewis, Dalin Li, Honghuang Lin, Chunyu Liu, Jiankang Liu, Kiang Liu, Xiaoming Liu, Yongmei Liu, William T. Longstreth, Cay Loria, Kathryn Lunetta, Aaron J. Mackey, Rachel Mackey, Ani Manichaikul, Taylor Maxwell, Barbara McKnight, James B. Meigs, Alanna C. Morrison, Solomon K. Musani, Josyf C. Mychaleckyj, Jennifer A. Nettleton, Kari North, Daniel O’Leary, Frank Ong, Walter Palmas, James S. Pankow, Nathan D. Pankratz, Shom Paul, Marco Perez, Sharina D. Person, Joseph Polak, Aaron R. Quinlan, Leslie J. Raffel, Vasan S. Ramachandran, Kenneth Rice, Jill P. Sanders, Pamela Schreiner, Sudha Seshadri, Steve Shea, Stephen Sidney, Kevin Silverstein, Nicholas L. Smith, Nona Sotoodehnia, Asoke Srinivasan, Kent Taylor, Fridtjof Thomas, Michael Y. Tsai, Kelly A. Volcik, Chrstina L. Wassel, Karol Watson, Gina Wei, Wendy White, Kerri L. Wiggins, Jemma B. Wilk, O. Dale Williams, Gregory Wilson, Phillip Wolf, Neil A. Zakai, John Hardy, James F. Meschia, Michael Nalls, Andrew Singleton, Brad Worrall, Michael J. Bamshad, Kathleen C. Barnes, Ibrahim Abdulhamid, Frank Accurso, Ran Anbar, Terri Beaty, Abigail Bigham, Phillip Black, Eugene Bleecker, Kati Buckingham, Anne Marie Cairns, Daniel Caplan, Barbara Chatfield, Aaron Chidekel, Michael Cho, David C. Christiani, James D. Crapo, Julia Crouch, Denise Daley, Anthony Dang, Hong Dang, Alicia De Paula, Joan DeCelie-Germana, Allen DozorMitch Drumm, Maynard Dyson, Julia Emerson, Mary J. Emond, Thomas Ferkol, Robert Fink, Cassandra Foster, Deborah Froh, Li Gao, William Gershan, Ronald L. Gibson, Elizabeth Godwin, Magdalen Gondor, Hector Gutierrez, Nadia N. Hansel, Paul M. Hassoun, Peter Hiatt, John E. Hokanson, Michelle Howenstine, Laura K. Hummer, Jamshed Kanga, Yoonhee Kim, Michael R. Knowles, Michael Konstan, Thomas Lahiri, Nan Laird, Christoph Lange, Lin Lin, Xihong Lin, Tin L. Louie, David Lynch, Barry Make, Thomas R. Martin, Steve C. Mathai, Rasika A. Mathias, John McNamara, Sharon McNamara, Deborah Meyers, Susan Millard, Peter Mogayzel, Richard Moss, Tanda Murray, Dennis Nielson, Blakeslee Noyes, Wanda O’Neal, David Orenstein, Brian O’Sullivan, Rhonda Pace, Peter Pare, H. Worth Parker, Mary Ann Passero, Elizabeth Perkett, Adrienne Prestridge, Nicholas M. Rafaels, Bonnie Ramsey, Elizabeth Regan, Clement Ren, George Retsch-Bogart, Michael Rock, Antony Rosen, Margaret Rosenfeld, Ingo Ruczinski, Andrew Sanford, David Schaeffer, Cindy Sell, Daniel Sheehan, Edwin K. Silverman, Don Sin, Terry Spencer, Jackie Stonebraker, Holly K. Tabor, Laurie Varlotta, Candelaria I. Vergara, Robert Weiss, Fred Wigley, Robert A. Wise, Fred A. Wright, Mark M. Wurfel, Robert Zanni, Fei Zou, Phil Green, Jay Shendure, Joshua M. Akey, Carlos D. Bustamante, Evan E. Eichler, P. Keolu Fox, Wenqing Fu, Adam Gordon, Simon Gravel, Jill M. Johnsen, Mengyuan Kan, Eimear E. Kenny, Jeffrey M. Kidd, Fremiet Lara-Garduno, Suzanne M. Leal, Dajiang J. Liu, Sean McGee, Timothy D. O’Connor, Bryan Paeper, Peggy D. Robertson, Jeffrey C. Staples, Jacob A. Tennessen, Gao Wang, Qian Yi, Rebecca Jackson, Garnet Anderson, Hoda Anton-Culver, Paul L. Auer, Shirley Beresford, Henry Black, Robert Brunner, Robert Brzyski, Dale Burwen, Bette Caan, Cara L. Carty, Rowan Chlebowski, Steven Cummings, J. David Curb, Charles B. Eaton, Leslie Ford, Stephanie M. Fullerton, Margery Gass, Nancy Geller, Gerardo Heiss, Barbara V. Howard, Li Hsu, Carolyn M. Hutter, John Ioannidis, Karen C. Johnson, Lewis Kuller, Andrea LaCroix, Kamakshi Lakshminarayan, Dorothy Lane, Norman Lasser, Erin LeBlanc, Kuo-Ping Li, Marian Limacher, Benjamin A. Logsdon, Shari Ludlam, JoAnn E. Manson, Karen Margolis, Lisa Martin, Joan McGowan, Keri L. Monda, Jane Morley Kotchen, Lauren Nathan, Judith Ockene, Mary Jo O’Sullivan, Lawrence S. Phillips, Ross L. Prentice, John Robbins, Jacques E. Rossouw, Haleh Sangi-Haghpeykar, Gloria E. Sarto, Sally Shumaker, Michael S. Simon, Marcia L. Stefanick, Evan Stein, Hua Tang, Kira C. Taylor, Cynthia A. Thomson, Timothy A. Thornton, Linda Van Horn, Mara Vitolins, Jean Wactawski-Wende, Robert Wallace, Sylvia Wassertheil-Smoller, Donglin Zeng, Deborah Applebaum-Bowden, Michael Feolo, Weiniu Gan, Dina N. Paltoo, Phyliss Sholinsky, Anne Sturcke, Epidemiology, and Internal Medicine

Subjects
Male, Genome-wide association study, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Gene Frequency, Receptors, Genotype, Dyslipidemias/blood, Receptors, LDL/genetics, Genetics(clinical), Exome, Genetics (clinical), Exome sequencing, Genetics, 0303 health sciences, Serine Endopeptidases, Single Nucleotide, Middle Aged, 3. Good health, Cholesterol, Phenotype, Genetic Code, Cholesterol, LDL/genetics, Female, lipids (amino acids, peptides, and proteins), Proprotein Convertases, Proprotein Convertase 9, Sequence Analysis, Adult, Apolipoproteins E/blood, LDL/genetics, Serine Endopeptidases/genetics, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Apolipoproteins E, SDG 3 - Good Health and Well-being, Humans, Polymorphism, Allele frequency, 030304 developmental biology, Genetic association, Aged, Dyslipidemias, PCSK9, DNA, Cholesterol, LDL, Lipase, Sequence Analysis, DNA, Receptors, LDL, Lipase/genetics, Proprotein Convertases/genetics, Follow-Up Studies, Genome-Wide Association Study
Abstract

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or

Published
2014

5. Detailed high-resolution three-dimensional simulations of OMEGA separated reactants inertial confinement fusion experiments

Author

R. C. Shah, Brian Haines, Kevin Silverstein, Malcolm M. Fowler, J. B. Wilhelmy, F. J. Marshall, Andreas Klein, Michael James Steinkamp, Robert Gore, Robert S. Rundberg, Gary Grim, A. C. Hayes-Sterbenz, Gerard Jungman, M. Boswell, Chad Forrest, and James R. Fincke

Subjects
Physics, Yield (engineering), Turbulence, Implosion, Plasma diffusion, Condensed Matter Physics, 01 natural sciences, 010305 fluids & plasmas, Computational physics, Deuterium, 0103 physical sciences, Nuclear fusion, Neutron, Atomic physics, 010306 general physics, Inertial confinement fusion
Abstract

We present results from the comparison of high-resolution three-dimensional (3D) simulations with data from the implosions of inertial confinement fusion capsules with separated reactants performed on the OMEGA laser facility. Each capsule, referred to as a “CD Mixcap,” is filled with tritium and has a polystyrene (CH) shell with a deuterated polystyrene (CD) layer whose burial depth is varied. In these implosions, fusion reactions between deuterium and tritium ions can occur only in the presence of atomic mix between the gas fill and shell material. The simulations feature accurate models for all known experimental asymmetries and do not employ any adjustable parameters to improve agreement with experimental data. Simulations are performed with the RAGE radiation-hydrodynamics code using an Implicit Large Eddy Simulation (ILES) strategy for the hydrodynamics. We obtain good agreement with the experimental data, including the DT/TT neutron yield ratios used to diagnose mix, for all burial depths of the deuterated shell layer. Additionally, simulations demonstrate good agreement with converged simulations employing explicit models for plasma diffusion and viscosity, suggesting that the implicit sub-grid model used in ILES is sufficient to model these processes in these experiments. In our simulations, mixing is driven by short-wavelength asymmetries and longer-wavelength features are responsible for developing flows that transport mixed material towards the center of the hot spot. Mix material transported by this process is responsible for most of the mix (DT) yield even for the capsule with a CD layer adjacent to the tritium fuel. Consistent with our previous results, mix does not play a significant role in TT neutron yield degradation; instead, this is dominated by the displacement of fuel from the center of the implosion due to the development of turbulent instabilities seeded by long-wavelength asymmetries. Through these processes, the long-wavelength asymmetries degrade TT yield more than the DT yield and thus bring DT/TT neutron yield ratios into agreement with experiment. Finally, we present a detailed comparison of the flows in 2D and 3D simulations.

Published
2016
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6. STAT5 antagonism of B cell superenhancer networks initiates progenitor B cell leukemia and predicts patient survival (HEM1P.222)

Author

Michael Farrar, Casey Katerndahl, Lynn Heltemes Harris, Mark Willette, christine Henzler, Rendong Yang, Kevin Silverstein, Seth Frietze, Hilde Schjerven, Laura Ramsey, Gregory Hubbard, Markus Muschen, and Steven Kornblau

Subjects
Immunology, Immunology and Allergy
Abstract

B cell Acute Lymphoblastic Leukemia (B-ALL) arises from the transformation of progenitor B cells. The transcription factor STAT5 is required for transformation but how STAT5 mediates this effect is unclear. Previous studies suggested that STAT5 only acts to promote survival of progenitor B cells. However, other roles for STAT5 in B cell development and B-ALL have not been explored. Here we show that STAT5 activation drives leukemia in cooperation with defects in a linear signaling pathway emanating from the pre-BCR, including Blnk, Btk, Prkcb, Nfkb1, and Ikzf1. Using microarray analysis and ChIP-Seq we demonstrate that STAT5 disrupts the function of superenhancer binding transcription factor networks that normally promote B cell development. STAT5 versus NFkB or IKAROS binding to these enhancers largely had opposing effects on target gene expression. The antagonism between STAT5 and IKAROS or NFκB has direct clinical relevance as the balance between these transcription factors affects patient outcome; patients with high ratios of active STAT5 to NFκB or IKAROS had more aggressive disease characterized by shorter remission and decreased survival. Thus, our studies illustrate how modest perturbations in two opposing transcriptional programs can have dramatic consequences for B cell development and transformation and how the degree of antagonism between these transcriptional programs ultimately predicts patient outcome to therapy.

Published
2015
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