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15 results on '"Tristan, Frum"'

1. hPSC-derived organoids: models of human development and disease

Author

Jason R. Spence and Tristan Frum

Subjects
0301 basic medicine, Cell signaling, Intestinal organoids, Disease, Computational biology, Review, Stem cells, Biology, Development, Organoids, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Disease modeling, Drug Discovery, Human development (biology), Organoid, Molecular Medicine, Stem cell, Induced pluripotent stem cell, 030217 neurology & neurosurgery, Genetics (clinical), Human
Abstract

Organoids derived from human pluripotent stem cells (hPSCs) have emerged as important models for investigating human-specific aspects of development and disease. Here we discuss hPSC-derived organoids through the lens of development—highlighting how stages of human development align with the development of hPSC-derived organoids in the tissue culture dish. Using hPSC-derived lung and intestinal organoids as examples, we discuss the value and application of such systems for understanding human biology, as well as strategies for enhancing organoid complexity and maturity.

Published
2020

2. SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation

Author

Richard Gregory, Luopin Wang, Nazish Malik, Nathalie Niyonzima, Charles J. Zhang, Jason R. Spence, Sonja Ghidelli-Disse, Matthew R. Olson, Marcus Bantscheff, Stefania Pittaluga, Tristan Frum, Majid Kazemian, Konstantinos D. Alysandratos, Jonathan Z. Sexton, Daniel Chauss, Darrell N. Kotton, Michail S. Lionakis, Carmen Mirabelli, Erin E. West, Didier Portilla, Bingyu Yan, Eva-Maria Nichols, Christiane E. Wobus, Tilo Freiwald, Shahram Kordasti, Martin Kolev, Behdad Afzali, Jack A. Bibby, Arian Laurence, and Claudia Kemper

Subjects
0301 basic medicine, Myeloid, Immunology, General Medicine, Biology, Complement factor B, Virus, C3-convertase, Complement system, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Interferon, Cell culture, 030220 oncology & carcinogenesis, Cancer research, medicine, Receptor, medicine.drug
Abstract

Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines, but did not affect NF-κB-regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB-signaling could potentially have clinical application for severe COVID-19.

Published
2021
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3. Culture conditions antagonize lineage-promoting signaling in the mouse blastocyst

Author

Amy Ralston and Tristan Frum

Subjects
0301 basic medicine, Embryology, Lineage (genetic), Cell Culture Techniques, Embryonic Development, Biology, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, medicine, Animals, Cell Lineage, Blastocyst, Cell specific, 030219 obstetrics & reproductive medicine, Lineage commitment, Obstetrics and Gynecology, Embryo, Cell Biology, Embryo, Mammalian, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Reproductive Medicine, embryonic structures, Ex vivo, Signal Transduction
Abstract

The mouse preimplantation embryo is a paradigm for discovery of the molecular principles governing formation of specific cell types during development. We show that conditions commonly used for ex vivo culture of preimplantation development are themselves antagonistic to a pathway that is critical for blastocyst lineage commitment.

Published
2020
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4. Understanding Human Lung Development through In Vitro Model Systems

Author

Ansley S. Conchola, Tristan Frum, Renee F. Conway, and Jason R. Spence

Subjects
Pluripotent Stem Cells, Organogenesis, organoid, Computational biology, Biology, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, Human lung, In vitro model, lung, 03 medical and health sciences, 0302 clinical medicine, Branching morphogenesis, bronchopulmonary dysplasia, medicine, Animals, Humans, 030304 developmental biology, 0303 health sciences, alveolosphere, Human development (humanity), medicine.anatomical_structure, human development, branching morphogenesis, signaling, 030217 neurology & neurosurgery
Abstract

An abundance of information about lung development in animal models exists; however, comparatively little is known about lung development in humans. Recent advances using primary human lung tissue combined with the use of human in vitro model systems, such as human pluripotent stem cell-derived tissue, have led to a growing understanding of the mechanisms governing human lung development. They have illuminated key differences between animal models and humans, underscoring the need for continued advancements in modeling human lung development and utilizing human tissue. This review discusses the use of human tissue and the use of human in vitro model systems that have been leveraged to better understand key regulators of human lung development and that have identified uniquely human features of development. This review also examines the implementation and challenges of human model systems and discusses how they can be applied to address knowledge gaps.

Published
2020

5. TEAD4, YAP1 and WWTR1 prevent the premature onset of pluripotency prior to the 16-cell stage

Author

Jennifer L Watts, Tristan FRUM, Amy Ralston, and Jennifer Watts

Subjects
Homeobox protein NANOG, Male, Pluripotent Stem Cells, Stem cell progenitors, Muscle Proteins, Cell Cycle Proteins, Mice, Transgenic, HIPPO signaling, Biology, Protein Serine-Threonine Kinases, Ectopic Gene Expression, 03 medical and health sciences, Mice, 0302 clinical medicine, SOX2, Animals, TEAD4, Preimplantation, Kinase activity, Molecular Biology, Psychological repression, Embryonic Stem Cells, 030304 developmental biology, Adaptor Proteins, Signal Transducing, 0303 health sciences, SOXB1 Transcription Factors, Tumor Suppressor Proteins, Gene Expression Regulation, Developmental, TEA Domain Transcription Factors, YAP-Signaling Proteins, Stem Cells and Regeneration, Embryo, Mammalian, 3. Good health, Cell biology, DNA-Binding Proteins, Blastocyst, Hippo signaling, embryonic structures, Trans-Activators, Ectopic expression, Female, sense organs, Stem cell, biological phenomena, cell phenomena, and immunity, 030217 neurology & neurosurgery, Developmental Biology, Transcription Factors
Abstract

In mice, pluripotent cells are thought to derive from cells buried inside the embryo around the 16-cell stage. Sox2 is the only pluripotency gene known to be expressed specifically within inside cells at this stage. To understand how pluripotency is established, we therefore investigated the mechanisms regulating the initial activation of Sox2 expression. Surprisingly, Sox2 expression initiated normally in the absence of both Nanog and Oct4 (Pou5f1), highlighting differences between embryo and stem cell models of pluripotency. However, we observed precocious ectopic expression of Sox2 prior to the 16-cell stage in the absence of Yap1, Wwtr1 and Tead4. Interestingly, the repression of premature Sox2 expression was sensitive to LATS kinase activity, even though LATS proteins normally do not limit activity of TEAD4, YAP1 and WWTR1 during these early stages. Finally, we present evidence for direct transcriptional repression of Sox2 by YAP1, WWTR1 and TEAD4. Taken together, our observations reveal that, while embryos are initially competent to express Sox2 as early as the four-cell stage, transcriptional repression prevents the premature expression of Sox2, thereby restricting the pluripotency program to the stage when inside cells are first created., Highlighted Article: The pluripotency marker SOX2 is not initially regulated by OCT4 and NANOG, but by HIPPO pathway members during the first 2 days of mouse embryogenesis.

Published
2019

6. TEAD4/YAP1/WWTR1 prevent the premature onset of pluripotency prior to the 16-cell stage

Author

Amy Ralston, Jennifer Watts, and Tristan Frum

Subjects
Homeobox protein NANOG, YAP1, 0303 health sciences, Embryo, Biology, 3. Good health, Cell biology, 03 medical and health sciences, 0302 clinical medicine, SOX2, embryonic structures, Ectopic expression, TEAD4, Stem cell, biological phenomena, cell phenomena, and immunity, Psychological repression, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

In the mouse embryo, pluripotent cells arise inside the embryo around the 16-cell stage. During these early stages, Sox2 is the only gene whose expression is known to be induced specifically within inside cells as they are established. To understand how pluripotent cells are created, we investigated the mechanisms regulating the initial activation of Sox2 expression. Surprisingly, Sox2 expression initiated normally in the absence of both Nanog and Oct4, highlighting differences between embryo and stem cell models of pluripotency. However, we observed precocious, ectopic expression of Sox2 prior to the 16-cell stage in the absence of Yap1, Wwtr1, and Tead4. Interestingly, the repression of premature Sox2 expression was sensitive to LATS1/2 activity, even though it normally does not limit TEAD4/YAP1/WWTR1 activity during these early stages. Finally, we present evidence for direct transcriptional repression of Sox2 by YAP1/WWTR1/TEAD4. Taken together, our observations reveal that, while embryos are initially competent to express Sox2 as early as the 4-cell stage, transcriptional repression prevents the premature expression of Sox2, thereby restricting the pluripotency program to the stage when inside cells are first created.

Published
2019
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7. Visualizing HIPPO Signaling Components in Mouse Early Embryonic Development

Author

Amy Ralston and Tristan Frum

Subjects
0303 health sciences, Hippo signaling pathway, animal structures, fungi, Cell fate determination, Biology, Embryonic stem cell, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Hippo signaling, 030220 oncology & carcinogenesis, Cell polarity, Signal transduction, Stem cell, Progenitor cell, 030304 developmental biology
Abstract

The HIPPO signaling pathway plays an early and essential role in mammalian embryogenesis. The earliest known roles for HIPPO signaling during mouse development include segregating fetal and extraembryonic lineages and establishing the pluripotent progenitors of embryonic stem (ES) cells. In the mouse early embryo, HIPPO signaling responds to multiple cell biological inputs, including cell polarization, cytoskeleton, and cell environment, to influence gene expression and the first cell fate decisions in development. Methods to monitor and manipulate HIPPO signaling in the mouse early embryo are fundamental to discovering mechanisms regulating pluripotency in vivo, but properties of the early embryo, such as small cell number and spherical architecture, pose unique challenges for signaling pathway analysis. Here, we share approaches for visualizing HIPPO signaling in mouse early embryos. In addition, these methods can be applied to visualize HIPPO signaling in other spherical or cystic structures comprised of relatively few cells, such as organoids, or for the examination of other signaling pathways in these contexts.

Published
2018
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8. HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo

Author

Tayler M Murphy, Tristan Frum, and Amy Ralston

Subjects
0301 basic medicine, Mouse, Gene Dosage, Cell Cycle Proteins, WWTR1, Mice, 0302 clinical medicine, Cell Movement, Cell polarity, CDX2 Transcription Factor, Biology (General), Protein Kinase C, Feedback, Physiological, YAP1, 0303 health sciences, General Neuroscience, Gene Expression Regulation, Developmental, Cell Differentiation, Mouse Embryonic Stem Cells, General Medicine, Cell biology, cell polarity, Hippo signaling, embryonic structures, Medicine, Research Article, Signal Transduction, Pluripotent Stem Cells, animal structures, QH301-705.5, Science, Protein Serine-Threonine Kinases, Cell fate determination, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, SOX2, Animals, Cell Lineage, Hippo Signaling Pathway, mammals, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Hippo signaling pathway, General Immunology and Microbiology, SOXB1 Transcription Factors, fungi, YAP-Signaling Proteins, Embryo, Mammalian, Phosphoproteins, pluripotency, Embryonic stem cell, 030104 developmental biology, Trans-Activators, sense organs, 030217 neurology & neurosurgery, Developmental Biology
Abstract

During mammalian development, the challenge for the embryo is to override intrinsic cellular plasticity to drive cells to distinct fates. Here, we unveil novel roles for the HIPPO signaling pathway in controlling cell positioning and expression of Sox2, the first marker of pluripotency in the mouse early embryo. We show that maternal and zygotic YAP1 and WWTR1 repress Sox2 while promoting expression of the trophectoderm gene Cdx2 in parallel. Yet, Sox2 is more sensitive than Cdx2 to Yap1/Wwtr1 dosage, leading cells to a state of conflicted cell fate when YAP1/WWTR1 activity is moderate. Remarkably, HIPPO signaling activity resolves conflicted cell fate by repositioning cells to the interior of the embryo, independent of its role in regulating Sox2 expression. Rather, HIPPO antagonizes apical localization of Par complex components PARD6B and aPKC. Thus, negative feedback between HIPPO and Par complex components ensure robust lineage segregation., eLife digest As an embryo develops, its cells divide, grow and migrate in specific patterns to build an organized collection of cells that go on to form our tissues and organs. One of the first steps – well before the embryo has implanted into the womb – is to allocate cells to make part of the placenta. Once this process is complete, the remaining cells continue building the organism. These cells are pluripotent, meaning they can develop into any part of the body. Scientists think that the embryo manages to sort ‘placenta cells’ from pluripotent ones with the help of certain proteins, which the mother has packaged into her eggs. To investigate this further, Frum et al. used genetic tools to track a specific gene called Sox2 that identifies pluripotent cells as soon as they are formed in mouse embryos. The experiments revealed that the mother places two closely related proteins known as YAP1 and WWTR1 within each egg, which help to make placenta cells different from pluripotent cells. Moreover, both proteins enable the embryo to segregate these two cell types to two different locations: placenta cells are moved to the outer layer of the embryo, while pluripotent cells are moved to the inside. Current technologies allow researchers to create pluripotent cells in the laboratory. But these approaches often result in error, failing to replicate the embryo’s natural ability. By studying how embryos form and arrange pluripotent cells, scientists hope to advance stem cell technology (which emerge from pluripotent cells). This may help to find new ways to heal damaged tissues and organs, or to treat or even prevent many diseases.

Published
2018
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10. AttrActin' Attention to Early Mouse Development

Author

Amy Ralston and Tristan Frum

Subjects
0301 basic medicine, Extramural, Cell, Embryogenesis, Embryonic Development, Embryo, Biology, Embryo, Mammalian, General Biochemistry, Genetics and Molecular Biology, Actins, Cell biology, 03 medical and health sciences, Mice, 030104 developmental biology, medicine.anatomical_structure, Blastocyst, medicine, Animals, Attention, Actin
Abstract

A new study by Zenker et al. uses time-lapse imaging to discover how dynamic actin movements contribute to epithelialization of living mouse embryos. Together with work from other labs, this study presents exciting new ways to think about the emergence of cell fates during mammalian development.

Published
2018

11. Pluripotency—What Does Cell Polarity Have to Do With It?

Author

Amy Ralston and Tristan Frum

Subjects
0301 basic medicine, Rex1, Cellular differentiation, Embryoid body, Biology, Embryonic stem cell, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Stem cell, Induced pluripotent stem cell, Reprogramming, Cell potency, 030217 neurology & neurosurgery
Abstract

Polarization is a mechanism commonly used by cells to establish asymmetries and create specialized subcellular functional domains. The process of cell polarization is especially important during mammalian development, when pluripotent cells are first established. Pluripotent cells are, by definition, capable of giving rise to the entire fetus. In addition, pluripotent stem cell lines can be derived from mammalian embryos and can be created by reprogramming differentiated cells. Understanding the molecular and cell biological differences between pluripotent and nonpluripotent cells is an important research direction in regenerative medicine. This chapter focuses on examining the role that cell polarization plays in establishing and maintaining pluripotency in the mouse embryo and in pluripotent stem cell lines. The literature shows that, in the early embryo, cell polarization is repressed in emerging pluripotent epiblast cells, while apicobasal polarization is established in multipotent cells of the extraembryonic lineages. Since polarization of extraembryonic cells is essential for defining which cells become pluripotent, cell polarization is indirectly responsible for establishing pluripotency in the embryo. Later, in the established pluripotent epiblast, cells polarize just before they exit pluripotency and commence differentiation. Just as multiple stages of pluripotency exist in the embryo, multiple pluripotent states exist among stem cell lines, ranging from naive to primed pluripotency. Mirroring the embryonic stages of pluripotency, polarity is associated with primed, and not naive, pluripotent stem cell lines. Therefore, in both embryos and in stem cell lines, cell polarization is a hallmark of decreased developmental potential, suggesting that the purpose of pluripotent cell polarization is to prepare cells for the next developmental goal: differentiation.

Published
2018
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12. Oct4 Cell-Autonomously Promotes Primitive Endoderm Development in the Mouse Blastocyst

Author

Chaoyang Wang, Hossein Amiri, Paul Robson, Tristan Frum, Michael A. Halbisen, and Amy Ralston

Subjects
Male, MAP Kinase Signaling System, cells, Fibroblast Growth Factor 4, Mice, Transgenic, Biology, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, GATA6 Transcription Factor, FGF4, Animals, Outbred Strains, medicine, Animals, Cell Lineage, Blastocyst, Molecular Biology, Embryonic Stem Cells, reproductive and urinary physiology, 030304 developmental biology, Homeodomain Proteins, Regulation of gene expression, 0303 health sciences, Endoderm, fungi, Gene Expression Regulation, Developmental, Nanog Homeobox Protein, Embryo, Cell Biology, Embryonic stem cell, Molecular biology, medicine.anatomical_structure, Epiblast, embryonic structures, Female, biological phenomena, cell phenomena, and immunity, Octamer Transcription Factor-3, 030217 neurology & neurosurgery, Developmental Biology
Abstract

SummaryIn embryonic stem (ES) cells and in early mouse embryos, the transcription factor Oct4 is an essential regulator of pluripotency. Oct4 transcriptional targets have been described in ES cell lines; however, the molecular mechanisms by which Oct4 regulates establishment of pluripotency in the epiblast (EPI) have not been fully elucidated. Here, we show that neither maternal nor zygotic Oct4 is required for the formation of EPI cells in the blastocyst. Rather, Oct4 is first required for development of the primitive endoderm (PE), an extraembryonic lineage. EPI cells promote PE fate in neighboring cells by secreting Fgf4, and Oct4 is required for expression of Fgf4, but we show that Oct4 promotes PE development cell-autonomously, downstream of Fgf4 and Mapk. Finally, we show that Oct4 is required for the expression of multiple EPI and PE genes as well as multiple metabolic pathways essential for the continued growth of the preimplantation embryo.

Published
2013
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13. The accessible chromatin landscape of the human genome

Author

Vishwanath R. Iyer, Lingyun Song, Michael O. Dorschner, Joshua M. Akey, Andrew B. Stergachis, Kristen Lee, Anthony Shafer, Shinny Vong, Amartya Sanyal, Hongzhu Qu, Audra K. Johnson, Ericka M. Johnson, Kavita Garg, Minerva E. Sanchez, Daniel Bates, Benjamin Vernot, George Stamatoyannopoulos, Tanya Kutyavin, Robert E. Thurman, Patrick A. Navas, Douglas Dunn, Eric Rynes, Bryan R. Lajoie, Matthew T. Maurano, Jeff Vierstra, Molly Weaver, Jason D. Lieb, Sam John, Alexias Safi, Lisa Boatman, Shane Neph, Zhancheng Zhang, Yongqi Yan, Bum Kyu Lee, Dimitra Lotakis, Zhuzhu Zhang, Gregory E. Crawford, Tristan Frum, Abigail K. Ebersol, Richard Sandstrom, Theresa K. Canfield, Eric Haugen, Erika Giste, Job Dekker, Muneesh Tewari, Alex Reynolds, Eric D. Nguyen, Fidencio Neri, Richard Humbert, Peter J. Sabo, Morgan Diegel, John A. Stamatoyannopoulos, Vaughn Roach, Hao Wang, Rajinder Kaul, Terrence S. Furey, Nathan C. Sheffield, R. Scott Hansen, Jeremy M. Simon, Shamil R. Sunyaev, Boris Lenhard, and Darin London

Subjects
Encyclopedias as Topic, Transcription, Genetic, DNA Footprinting, ATAC-seq, Computational biology, Regulatory Sequences, Nucleic Acid, Biology, DNase-Seq, Article, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Mutation Rate, Deoxyribonuclease I, Humans, Promoter Regions, Genetic, Enhancer, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Genome, Human, Molecular Sequence Annotation, Promoter, DNA, Genomics, DNA Methylation, Chromatin, DNA-Binding Proteins, DNA methylation, Human genome, DNase I hypersensitive site, Transcription Initiation Site, 030217 neurology & neurosurgery, Transcription Factors
Abstract

DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify ∼2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect ∼580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation. An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. This paper describes the first extensive map of human DNaseI hypersensitive sites — markers of regulatory DNA — in 125 diverse cell and tissue types. Integration of this information with other data sets generated by ENCODE (Encyclopedia of DNA Elements) identified new relationships between chromatin accessibility, transcription, DNA methylation and regulatory-factor occupancy patterns. Evolutionary-conservation analysis revealed signatures of recent functional constraint within DNaseI hypersensitive sites.

Published
2012

14. An integrated encyclopedia of DNA elements in the human genome

Author

Robert Altshuler, Laura Elnitski, Michael Anaya, Alec Victorsen, Deborah Winter, Javier Herrero, Katherine Varley, Andrea Sboner, Oscar Junhong Luo, Marco Mariotti, Cristina Sisu, Mike Kay, Timothy Dreszer, Jane Loveland, Alexandra Bignell, Ewan Birney, Tim @timjph Hubbard, Kuljeet Sandhu, Eric Haugen, Chris Gunter, Alexej Abyzov, Lucas Ward, Georgi Marinov, Michael Pazin, Thomas Gingeras, Alexander Dobin, Kimberly Foss, Xianjun Dong, Benoit Miotto, Piotr Mieczkowski, Cedric Notredame, Andrew Berry, Shawn Gillespie, Axel Visel, Shawn Levy, Richard Sandstrom, Jose M Gonzalez, Melissa Fullwood, Timo Lassmann, Michael Tress, Julien Lagarde, Kevin Yip, Leslie Adams, Sylvain Foissac, Bronwen Aken, Piero Carninci, Suganthi Balasubramanian, Andrea Tanzer, Sarah Djebali, Michael Hoffman, Gloria Despacio-Reyes, Peter Park, Felix Kokocinski, Katherine Fisher-Aylor, Juan M Vaquerizas, Peggy Farnham, Patrick Collins, Amonida Zadissa, Pedro Ferreira, Philippe Batut, Michael Snyder, Electra Tapanari, Adam Frankish, Paul Flicek, AMARTYA SANYAL, Tyler Alioto, Giovanni Bussotti, Laurence Meyer, Jingyi Jessica Li, Matthew Blow, Tristan FRUM, Roger Alexander, Rory Johnson, Charles Steward, Meizhen Zheng, Margus Lukk, Ross Hardison, Claire Davidson, Gary Saunders, Alan Boyle, Luiz Penalva, Rajinder Kaul, Lazaro Centanin, Florencia Pauli Behn, Thomas Derrien, Nathan Sheffield, Toby Hunt, Eric Nguyen, Jeff Vierstra, Konrad Karczewski, Kimberly Bell, Yanbao Yu, Hagen U Tilgner, James Taylor, Balázs Bánfai, Catherine Snow, Benjamin Vernot, Stephan Kirchmaier, Michael Sammeth, Steven Wilder, Angelika Merkel, Joanna Mieczkowska, Guoliang Li, Wei Lin, Jennifer Harrow, Thomas Oliver Auer, Daniel Barrell, Eddie Park, Alvis Brazma, Hazuki Takahashi, Nathan Johnson, Daniel Sobral, Terry Furey, Alexandre Reymond, Jonathan Mudge, Anshul Kundaje, Jose Rodriguez, Akshay Bhinge, James Gilbert, Jakub Karczewski, Venkat Malladi, Troy Whitfield, Orion Buske, Ian Dunham, Jennifer Moran, Joachim Wittbrodt, Charles B. Epstein, Laurens Wilming, Jason Gertz, Joshua Akey, Joel Rozowsky, Laboratoire de Génétique Cellulaire (LGC), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), National Human Genome Research Institute (NHGRI), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Antonarakis, Stylianos, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Altshuler, Robert Charles, Ernst, Jason, Kellis, Manolis, Kheradpour, Pouya, Ward, Lucas D., Eaton, Matthew Lucas, Hendrix, David A., Jungreis, Irwin, Lin, Michael F., Washietl, Stefan, Lists of participants and their affiliations appear at the end of the paper and in the 'Collaboration/Projet' field., The Consortium is funded by grants from the NHGRI as follows: production grants: U54HG004570 (B. E. Bernstein), U01HG004695 (E. Birney), U54HG004563 (G. E. Crawford), U54HG004557 (T. R. Gingeras), U54HG004555 (T. J. Hubbard), U41HG004568 (W. J. Kent), U54HG004576 (R. M. Myers), U54HG004558 (M. Snyder), U54HG004592 (J. A. Stamatoyannopoulos). Pilot grants: R01HG003143 (J. Dekker), RC2HG005591 and R01HG003700 (M. C. Giddings), R01HG004456-03 (Y. Ruan), U01HG004571 (S. A. Tenenbaum), U01HG004561 (Z. Weng), RC2HG005679 (K. P. White). This project was supported in part by American Recovery and Reinvestment Act (ARRA) funds from the NHGRI through grants U54HG004570, U54HG004563, U41HG004568, U54HG004592, R01HG003143, RC2HG005591, R01HG003541,U01HG004561,RC2HG005679andR01HG003988(L. Pennacchio). In addition, work from NHGRI Groups was supported by the Intramural Research Program of the NHGRI (L. Elnitski, ZIAHG200323, E. H. Margulies, ZIAHG200341). Research in the Pennachio laboratory was performed at Lawrence Berkeley National Laboratory and at the United States Department of Energy Joint Genome Institute, Department of Energy Contract DE-AC02-05CH11231, University of California., Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R, Khatun J, Lajoie BR, Landt SG, Lee BK, Pauli F, Rosenbloom KR, Sabo P, Safi A, Sanyal A, Shoresh N, Simon JM, Song L, Trinklein ND, Altshuler RC, Birney E, Brown JB, Cheng C, Djebali S, Dong X, Dunham I, Ernst J, Furey TS, Gerstein M, Giardine B, Greven M, Hardison RC, Harris RS, Herrero J, Hoffman MM, Iyer S, Kellis M, Khatun J, Kheradpour P, Kundaje A, Lassmann T, Li Q, Lin X, Marinov GK, Merkel A, Mortazavi A, Parker SC, Reddy TE, Rozowsky J, Schlesinger F, Thurman RE, Wang J, Ward LD, Whitfield TW, Wilder SP, Wu W, Xi HS, Yip KY, Zhuang J, Pazin MJ, Lowdon RF, Dillon LA, Adams LB, Kelly CJ, Zhang J, Wexler JR, Green ED, Good PJ, Feingold EA, Bernstein BE, Birney E, Crawford GE, Dekker J, Elnitski L, Farnham PJ, Gerstein M, Giddings MC, Gingeras TR, Green ED, Guigó R, Hardison RC, Hubbard TJ, Kellis M, Kent W, Lieb JD, Margulies EH, Myers RM, Snyder M, Stamatoyannopoulos JA, Tenenbaum SA, Weng Z, White KP, Wold B, Khatun J, Yu Y, Wrobel J, Risk BA, Gunawardena HP, Kuiper HC, Maier CW, Xie L, Chen X, Giddings MC, Bernstein BE, Epstein CB, Shoresh N, Ernst J, Kheradpour P, Mikkelsen TS, Gillespie S, Goren A, Ram O, Zhang X, Wang L, Issner R, Coyne MJ, Durham T, Ku M, Truong T, Ward LD, Altshuler RC, Eaton ML, Kellis M, Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Röder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Batut P, Bell I, Bell K, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena HP, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Li G, Luo OJ, Park E, Preall JB, Presaud K, Ribeca P, Risk BA, Robyr D, Ruan X, Sammeth M, Sandhu KS, Schaeffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Hayashizaki Y, Harrow J, Gerstein M, Hubbard TJ, Reymond A, Antonarakis SE, Hannon GJ, Giddings MC, Ruan Y, Wold B, Carninci P, Guigó R, Gingeras TR, Rosenbloom KR, Sloan CA, Learned K, Malladi VS, Wong MC, Barber GP, Cline MS, Dreszer TR, Heitner SG, Karolchik D, Kent W, Kirkup VM, Meyer LR, Long JC, Maddren M, Raney BJ, Furey TS, Song L, Grasfeder LL, Giresi PG, Lee BK, Battenhouse A, Sheffield NC, Simon JM, Showers KA, Safi A, London D, Bhinge AA, Shestak C, Schaner MR, Kim SK, Zhang ZZ, Mieczkowski PA, Mieczkowska JO, Liu Z, McDaniell RM, Ni Y, Rashid NU, Kim MJ, Adar S, Zhang Z, Wang T, Winter D, Keefe D, Birney E, Iyer VR, Lieb JD, Crawford GE, Li G, Sandhu KS, Zheng M, Wang P, Luo OJ, Shahab A, Fullwood MJ, Ruan X, Ruan Y, Myers RM, Pauli F, Williams BA, Gertz J, Marinov GK, Reddy TE, Vielmetter J, Partridge E, Trout D, Varley KE, Gasper C, Bansal A, Pepke S, Jain P, Amrhein H, Bowling KM, Anaya M, Cross MK, King B, Muratet MA, Antoshechkin I, Newberry KM, McCue K, Nesmith AS, Fisher-Aylor KI, Pusey B, DeSalvo G, Parker SL, Balasubramanian S, Davis NS, Meadows SK, Eggleston T, Gunter C, Newberry J, Levy SE, Absher DM, Mortazavi A, Wong WH, Wold B, Blow MJ, Visel A, Pennachio LA, Elnitski L, Margulies EH, Parker SC, Petrykowska HM, Abyzov A, Aken B, Barrell D, Barson G, Berry A, Bignell A, Boychenko V, Bussotti G, Chrast J, Davidson C, Derrien T, Despacio-Reyes G, Diekhans M, Ezkurdia I, Frankish A, Gilbert J, Gonzalez JM, Griffiths E, Harte R, Hendrix DA, Howald C, Hunt T, Jungreis I, Kay M, Khurana E, Kokocinski F, Leng J, Lin MF, Loveland J, Lu Z, Manthravadi D, Mariotti M, Mudge J, Mukherjee G, Notredame C, Pei B, Rodriguez JM, Saunders G, Sboner A, Searle S, Sisu C, Snow C, Steward C, Tanzer A, Tapanari E, Tress ML, van Baren MJ, Walters N, Washietl S, Wilming L, Zadissa A, Zhang Z, Brent M, Haussler D, Kellis M, Valencia A, Gerstein M, Reymond A, Guigó R, Harrow J, Hubbard TJ, Landt SG, Frietze S, Abyzov A, Addleman N, Alexander RP, Auerbach RK, Balasubramanian S, Bettinger K, Bhardwaj N, Boyle AP, Cao AR, Cayting P, Charos A, Cheng Y, Cheng C, Eastman C, Euskirchen G, Fleming JD, Grubert F, Habegger L, Hariharan M, Harmanci A, Iyengar S, Jin VX, Karczewski KJ, Kasowski M, Lacroute P, Lam H, Lamarre-Vincent N, Leng J, Lian J, Lindahl-Allen M, Min R, Miotto B, Monahan H, Moqtaderi Z, Mu XJ, O'Geen H, Ouyang Z, Patacsil D, Pei B, Raha D, Ramirez L, Reed B, Rozowsky J, Sboner A, Shi M, Sisu C, Slifer T, Witt H, Wu L, Xu X, Yan KK, Yang X, Yip KY, Zhang Z, Struhl K, Weissman SM, Gerstein M, Farnham PJ, Snyder M, Tenenbaum SA, Penalva LO, Doyle F, Karmakar S, Landt SG, Bhanvadia RR, Choudhury A, Domanus M, Ma L, Moran J, Patacsil D, Slifer T, Victorsen A, Yang X, Snyder M, Auer T, Centanin L, Eichenlaub M, Gruhl F, Heermann S, Hoeckendorf B, Inoue D, Kellner T, Kirchmaier S, Mueller C, Reinhardt R, Schertel L, Schneider S, Sinn R, Wittbrodt B, Wittbrodt J, Weng Z, Whitfield TW, Wang J, Collins PJ, Aldred SF, Trinklein ND, Partridge EC, Myers RM, Dekker J, Jain G, Lajoie BR, Sanyal A, Balasundaram G, Bates DL, Byron R, Canfield TK, Diegel MJ, Dunn D, Ebersol AK, Frum T, Garg K, Gist E, Hansen R, Boatman L, Haugen E, Humbert R, Jain G, Johnson AK, Johnson EM, Kutyavin TV, Lajoie BR, Lee K, Lotakis D, Maurano MT, Neph SJ, Neri FV, Nguyen ED, Qu H, Reynolds AP, Roach V, Rynes E, Sabo P, Sanchez ME, Sandstrom RS, Sanyal A, Shafer AO, Stergachis AB, Thomas S, Thurman RE, Vernot B, Vierstra J, Vong S, Wang H, Weaver MA, Yan Y, Zhang M, Akey JM, Bender M, Dorschner MO, Groudine M, MacCoss MJ, Navas P, Stamatoyannopoulos G, Kaul R, Dekker J, Stamatoyannopoulos JA, Dunham I, Beal K, Brazma A, Flicek P, Herrero J, Johnson N, Keefe D, Lukk M, Luscombe NM, Sobral D, Vaquerizas JM, Wilder SP, Batzoglou S, Sidow A, Hussami N, Kyriazopoulou-Panagiotopoulou S, Libbrecht MW, Schaub MA, Kundaje A, Hardison RC, Miller W, Giardine B, Harris RS, Wu W, Bickel PJ, Banfai B, Boley NP, Brown JB, Huang H, Li Q, Li JJ, Noble WS, Bilmes JA, Buske OJ, Hoffman MM, Sahu AD, Kharchenko PV, Park PJ, Baker D, Taylor J, Weng Z, Iyer S, Dong X, Greven M, Lin X, Wang J, Xi HS, Zhuang J, Gerstein M, Alexander RP, Balasubramanian S, Cheng C, Harmanci A, Lochovsky L, Min R, Mu XJ, Rozowsky J, Yan KK, Yip KY, Birney E., and Miotto, Benoit

Subjects
Encyclopedias as Topic, [SDV]Life Sciences [q-bio], DNA Footprinting, Genoma humà, Binding Sites/genetics, Histones/chemistry/metabolism, 0302 clinical medicine, Exons/genetics, ddc:576.5, 0303 health sciences, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], DNA-Binding Proteins/metabolism, region, Chemistry, Genetic Predisposition to Disease/genetics, Genomics, Polymorphism, Single Nucleotide/genetics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Neoplasms/genetics, Chromatin, Cell biology, in vivo, Genetic Variation/genetics, 030220 oncology & carcinogenesis, Deoxyribonuclease I/metabolism, Proteins/genetics, transcription factor-binding, chromosome conformation capture, DNA Methylation/genetics, Chromosomes, Human/genetics/metabolism, Chromatin Immunoprecipitation, Mammals/genetics, DNA/genetics, determinant, Article, 03 medical and health sciences, map, Animals, Humans, Transcription Factors/metabolism, Alleles, mouse, 030304 developmental biology, Transcription, Genetic/genetics, Chromatin/genetics/metabolism, Sequence Analysis, RNA, human cell, Molecular Sequence Annotation, Regulatory Sequences, Nucleic Acid/genetics, Promoter Regions, Genetic/genetics, DNA binding site, Genòmica, Genome, Human/genetics, chromatin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genètica, Genome-Wide Association Study
Abstract

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. The Consortium is funded by grants from the NHGRI as follows: production grants: U54HG004570 (B. E. Bernstein); U01HG004695 (E. Birney); U54HG004563 (G. E. Crawford); U54HG004557 (T. R. Gingeras); U54HG004555 (T. J. Hubbard); U41HG004568 /n(W. J. Kent); U54HG004576 (R. M. Myers); U54HG004558 (M. Snyder);/nU54HG004592 (J. A. Stamatoyannopoulos). Pilot grants: R01HG003143 (J. Dekker); RC2HG005591 and R01HG003700 (M. C. Giddings); R01HG004456-03 (Y. Ruan); U01HG004571 (S. A. Tenenbaum); U01HG004561 (Z. Weng); RC2HG005679 (K. P. White). This project was supported in part by American Recovery and/nReinvestment Act (ARRA) funds from the NHGRI through grants U54HG004570, U54HG004563, U41HG004568, U54HG004592, R01HG003143, RC2HG005591,R01HG003541, U01HG004561, RC2HG005679andR01HG003988(L. Pennacchio). In addition, work from NHGRI Groups was supported by the Intramural Research/nProgram of the NHGRI (L. Elnitski, ZIAHG200323; E. H. Margulies, ZIAHG200341). Research in the Pennachio laboratory was performed at Lawrence Berkeley National Laboratory and at the United States Department of Energy Joint Genome Institute, Department of Energy Contract DE-AC02-05CH11231, University of California.

Published
2012
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15. A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

Author

Zhi Lu, Giltae Song, Troy W. Whitfield, Vishwanath R. Iyer, Teresa Vales, Angelika Merkel, Max Libbrecht, David Haussler, Ting Wang, Kristen Lee, Lingyun Song, Richard M. Myers, Alfonso Valencia, Rachel A. Harte, Xiaoqin Xu, Lucas D. Ward, Hazuki Takahashi, Nathan C. Sheffield, Thomas Derrien, Georgi K. Marinov, Eric D. Nguyen, Bernard B. Suh, Brian J. Raney, Richard Sandstrom, Thomas D. Tullius, Benoit Miotto, Alexander Dobin, Youhan Xu, Lukas Habegger, Ian Dunham, Brian A. Risk, Paul G. Giresi, Morgan C. Giddings, Hualin Xi, Anshul Kundaje, Robert S. Harris, Devin Absher, Peter J. Bickel, Yanbao Yu, Browen Aken, Colin Kingswood, Bryan R. Lajoie, Peter J. Good, Katrina Learned, Laura Elnitski, Shirley Pepke, Brandon King, Piero Carninci, Xinqiong Yang, Ghia Euskirchen, Kathryn Beal, Christelle Borel, Michael Muratet, Robert L. Grossman, David G. Knowles, Zarmik Moqtaderi, Veronika Boychenko, Steven P. Wilder, Michael L. Tress, Florencia Pauli, Alan P. Boyle, Andrea Tanzer, Philipp Kapranov, Serafim Batzoglou, Audra K. Johnson, Jun Neri, Nitin Bhardwaj, Elise A. Feingold, Venkat S. Malladi, Michael M. Hoffman, William Stafford Noble, Andrea Sboner, Mark Gerstein, Stephanie L. Parker, Jacqueline Dumais, Felix Schlesinger, Deborah R. Winter, Randall H. Brown, Thanh Truong, Rebecca F. Lowdon, Paolo Ribeca, Brooke Rhead, Peggy J. Farnham, Krista Thibeault, Terrence S. Furey, Donna Karolchik, Alec Victorsen, Xiaoan Ruan, Rehab F. Abdelhamid, Amy S. Nesmith, Jing Wang, Nicholas M. Luscombe, Alina R. Cao, Diane Trout, Teri Slifer, Peter E. Newburger, Cricket A. Sloan, Dimitra Lotakis, Stephen M. J. Searle, Ali Mortazavi, Alexandra Bignell, Alex Reynolds, Orion J. Buske, Chris Zaleski, Theresa K. Canfield, Ian Bell, Jin Lian, Vanessa K. Swing, Katalin Toth Fejes, Catherine Ucla, Robert E. Thurman, Jacqueline Chrast, Wei Lin, Tim Hubbard, Gary Saunders, Minyi Shi, Vihra Sotirova, Sherman M. Weissman, Jason D. Lieb, Richard Humbert, Kevin M. Bowling, Assaf Gordon, Tarjei S. Mikkelsen, Jing Leng, Thomas R. Gingeras, Fabian Grubert, Nader Jameel, Jost Vielmetter, Hannah Monahan, Preti Jain, Lindsay L. Waite, Tony Shafer, Joel Rozowsky, Michael Coyne, Brian Reed, M. Kay, Harsha P. Gunawardena, Ross C. Hardison, Gavin Sherlock, Alexandra Charos, Joseph D. Fleming, Ann S. Zweig, Jason Gertz, Rajinder Kaul, Xianjun Dong, Alexandre Reymond, Carrie A. Davis, Haiyan Huang, Chao Cheng, Marco Mariotti, Phil Lacroute, Jason A. Dilocker, Kenneth McCue, R. Robilotto, Stylianos E. Antonarakis, Sridar V. Chittur, Justin Jee, Barbara J. Wold, Sudipto K. Chakrabortty, Erica Dumais, Amartya Sanyal, Nathan Boley, Tianyuan Wang, Julien Lagarde, Anthony Kirilusha, Jonathan B. Preall, Kevin Roberts, Erika Giste, Hugo Y. K. Lam, Alvis Brazma, Gregory J. Hannon, Eric Rynes, Philippe Batut, Kevin Struhl, Margus Lukk, Manching Ku, Suganthi Balasubramanian, Sonali Jha, Jorg Drenkow, W. James Kent, Michael Snyder, Jie Wang, Anna Battenhouse, Charles B. Epstein, Rami Rauch, Christopher Shestak, John A. Stamatoyannopoulos, Gaurab Mukherjee, Cédric Howald, Tanya Kutyavin, Huaien Wang, Scott A. Tenenbaum, Wan Ting Poh, Kate R. Rosenbloom, Manolis Kellis, Pauline A. Fujita, Linfeng Wu, Anita Bansal, Molly Weaver, Linda L. Grasfeder, Peter J. Sabo, Qiang Li, Melissa S. Cline, Robert M. Kuhn, Darin London, Seth Frietze, Atif Shahab, Shane Neph, Damian Keefe, James B. Brown, Mark Diekhans, Webb Miller, Katherine Aylor Fisher, Jiang Du, Hadar H. Sheffer, Sarah Djebali, Frank Doyle, Nathan Lamarre-Vincent, Chia-Lin Wei, Laura A.L. Dillon, Jennifer Harrow, Robert C. Altshuler, Tyler Alioto, Raymond K. Auerbach, Adam Frankish, Rebekka O. Sprouse, Patrick J. Collins, E. Christopher Partridge, Zheng Liu, Yoichiro Shibata, Elliott H. Margulies, Abigail K. Ebersol, Kimberly A. Showers, Eric D. Green, Krishna M. Roskin, Job Dekker, Barbara N. Pusey, Ekta Khurana, Gilberto DeSalvo, Yijun Ruan, Hao Wang, Jainab Khatun, Henriette O'Geen, Alexej Abyzov, Brian Williams, Ryan M. McDaniell, Maya Kasowski, Manoj Hariharan, Felix Kokocinski, Gloria Despacio-Reyes, Zhancheng Zhang, Subhradip Karmakar, Ewan Birney, Koon-Kiu Yan, Xian Chen, Shinny Vong, Daniel Sobral, Nick Bild, Seul K.C. Kim, Timo Lassmann, Li Wang, Minerva E. Sanchez, Vaughan Roach, Theodore Gibson, Stephen C. J. Parker, Michael F. Lin, Patrick A. Navas, Laurence R. Meyer, Luiz O. F. Penalva, Bradley E. Bernstein, Kevin P. White, Emilie Aït Yahya Graison, Juan M. Vaquerizas, Sushma Iyengar, Kimberly M. Newberry, Akshay Bhinge, Xiaolan Zhang, Kim Bell, Yoshihide Hayashizaki, Lucas Lochovsky, Noam Shoresh, Hagen Tilgner, Philip Cayting, Dorrelyn Patacsil, Timothy E. Reddy, Eric Haugen, Katherine E. Varley, M. van Baren, Nathan D. Trinklein, Bum Kyu Lee, Tristan Frum, Marianne Lindahl-Allen, Timothy Durham, Roderic Guigó, Christopher W. Maier, Micha Sammeth, Debasish Raha, Timothy R. Dreszer, Benedict Paten, Robbyn Issner, Michael R. Brent, Kevin Y. Yip, Kim Blahnik, Jason Ernst, Zhiping Weng, Henry Amrhein, Arend Sidow, Javier Herrero, Hui Gao, Stephen G. Landt, Pouya Kheradpour, Galt P. Barber, Gregory E. Crawford, Toby Hunt, HudsonAlpha Institute for Biotechnology [Huntsville, AL], ENCODE Project Consortium : Myers RM, Stamatoyannopoulos J, Snyder M, Dunham I, Hardison RC, Bernstein BE, Gingeras TR, Kent WJ, Birney E, Wold B, Crawford GE, Bernstein BE, Epstein CB, Shoresh N, Ernst J, Mikkelsen TS, Kheradpour P, Zhang X, Wang L, Issner R, Coyne MJ, Durham T, Ku M, Truong T, Ward LD, Altshuler RC, Lin MF, Kellis M, Gingeras TR, Davis CA, Kapranov P, Dobin A, Zaleski C, Schlesinger F, Batut P, Chakrabortty S, Jha S, Lin W, Drenkow J, Wang H, Bell K, Gao H, Bell I, Dumais E, Dumais J, Antonarakis SE, Ucla C, Borel C, Guigo R, Djebali S, Lagarde J, Kingswood C, Ribeca P, Sammeth M, Alioto T, Merkel A, Tilgner H, Carninci P, Hayashizaki Y, Lassmann T, Takahashi H, Abdelhamid RF, Hannon G, Fejes-Toth K, Preall J, Gordon A, Sotirova V, Reymond A, Howald C, Graison E, Chrast J, Ruan Y, Ruan X, Shahab A, Ting Poh W, Wei CL, Crawford GE, Furey TS, Boyle AP, Sheffield NC, Song L, Shibata Y, Vales T, Winter D, Zhang Z, London D, Wang T, Birney E, Keefe D, Iyer VR, Lee BK, McDaniell RM, Liu Z, Battenhouse A, Bhinge AA, Lieb JD, Grasfeder LL, Showers KA, Giresi PG, Kim SK, Shestak C, Myers RM, Pauli F, Reddy TE, Gertz J, Partridge EC, Jain P, Sprouse RO, Bansal A, Pusey B, Muratet MA, Varley KE, Bowling KM, Newberry KM, Nesmith AS, Dilocker JA, Parker SL, Waite LL, Thibeault K, Roberts K, Absher DM, Wold B, Mortazavi A, Williams B, Marinov G, Trout D, Pepke S, King B, McCue K, Kirilusha A, DeSalvo G, Fisher-Aylor K, Amrhein H, Vielmetter J, Sherlock G, Sidow A, Batzoglou S, Rauch R, Kundaje A, Libbrecht M, Margulies EH, Parker SC, Elnitski L, Green ED, Hubbard T, Harrow J, Searle S, Kokocinski F, Aken B, Frankish A, Hunt T, Despacio-Reyes G, Kay M, Mukherjee G, Bignell A, Saunders G, Boychenko V, Van Baren M, Brown RH, Khurana E, Balasubramanian S, Zhang Z, Lam H, Cayting P, Robilotto R, Lu Z, Guigo R, Derrien T, Tanzer A, Knowles DG, Mariotti M, James Kent W, Haussler D, Harte R, Diekhans M, Kellis M, Lin M, Kheradpour P, Ernst J, Reymond A, Howald C, Graison EA, Chrast J, Tress M, Rodriguez JM, Snyder M, Landt SG, Raha D, Shi M, Euskirchen G, Grubert F, Kasowski M, Lian J, Cayting P, Lacroute P, Xu Y, Monahan H, Patacsil D, Slifer T, Yang X, Charos A, Reed B, Wu L, Auerbach RK, Habegger L, Hariharan M, Rozowsky J, Abyzov A, Weissman SM, Gerstein M, Struhl K, Lamarre-Vincent N, Lindahl-Allen M, Miotto B, Moqtaderi Z, Fleming JD, Newburger P, Farnham PJ, Frietze S, O'Geen H, Xu X, Blahnik KR, Cao AR, Iyengar S, Stamatoyannopoulos JA, Kaul R, Thurman RE, Wang H, Navas PA, Sandstrom R, Sabo PJ, Weaver M, Canfield T, Lee K, Neph S, Roach V, Reynolds A, Johnson A, Rynes E, Giste E, Vong S, Neri J, Frum T, Johnson EM, Nguyen ED, Ebersol AK, Sanchez ME, Sheffer HH, Lotakis D, Haugen E, Humbert R, Kutyavin T, Shafer T, Dekker J, Lajoie BR, Sanyal A, James Kent W, Rosenbloom KR, Dreszer TR, Raney BJ, Barber GP, Meyer LR, Sloan CA, Malladi VS, Cline MS, Learned K, Swing VK, Zweig AS, Rhead B, Fujita PA, Roskin K, Karolchik D, Kuhn RM, Haussler D, Birney E, Dunham I, Wilder SP, Keefe D, Sobral D, Herrero J, Beal K, Lukk M, Brazma A, Vaquerizas JM, Luscombe NM, Bickel PJ, Boley N, Brown JB, Li Q, Huang H, Gerstein M, Habegger L, Sboner A, Rozowsky J, Auerbach RK, Yip KY, Cheng C, Yan KK, Bhardwaj N, Wang J, Lochovsky L, Jee J, Gibson T, Leng J, Du J, Hardison RC, Harris RS, Song G, Miller W, Haussler D, Roskin K, Suh B, Wang T, Paten B, Noble WS, Hoffman MM, Buske OJ, Weng Z, Dong X, Wang J, Xi H, Tenenbaum SA, Doyle F, Penalva LO, Chittur S, Tullius TD, Parker SC, White KP, Karmakar S, Victorsen A, Jameel N, Bild N, Grossman RL, Snyder M, Landt SG, Yang X, Patacsil D, Slifer T, Dekker J, Lajoie BR, Sanyal A, Weng Z, Whitfield TW, Wang J, Collins PJ, Trinklein ND, Partridge EC, Myers RM, Giddings MC, Chen X, Khatun J, Maier C, Yu Y, Gunawardena H, Risk B, Feingold EA, Lowdon RF, Dillon LA, Good PJ, Harrow J, Searle S., Becker, Peter B, Broad Institute of MIT and Harvard, Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Department of Physics, Kellis, Manolis, Epstein, Charles B., Bernstein, Bradley E., Shoresh, Noam, Ernst, Jason, Mikkelsen, Tarjei Sigurd, Kheradpour, Pouya, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Ward, Lucas D., Altshuler, Robert Charles, Lin, Michael F., ENCODE Project Consortium, Antonarakis, Stylianos, and Miotto, Benoit

Subjects
RNA, Messenger/genetics, [SDV]Life Sciences [q-bio], Messenger, Genoma humà, Genome, Medical and Health Sciences, 0302 clinical medicine, Models, ddc:576.5, Biology (General), Conserved Sequence, Genetics, 0303 health sciences, General Neuroscience, RNA-Binding Proteins, Genomics, Biological Sciences, Chromatin, 3. Good health, [SDV] Life Sciences [q-bio], DNA-Binding Proteins, Gene Components, 030220 oncology & carcinogenesis, DNA methylation, Encyclopedia, HIV/AIDS, Proteïnes de la sang -- Aspectes genètics, General Agricultural and Biological Sciences, Databases, Nucleic Acid, Human, Research Article, Quality Control, Process (engineering), QH301-705.5, 1.1 Normal biological development and functioning, Computational biology, Biology, ENCODE, General Biochemistry, Genetics and Molecular Biology, Chromatin/metabolism, Vaccine Related, 03 medical and health sciences, Databases, Genetic, Underpinning research, Humans, RNA, Messenger, RNA-Binding Proteins/genetics/metabolism, Vaccine Related (AIDS), Gene, 030304 developmental biology, Internet, General Immunology and Microbiology, Nucleic Acid, Agricultural and Veterinary Sciences, Base Sequence, Models, Genetic, Genome, Human, Prevention, Human Genome, Computational Biology, DNA Methylation, ENCODE Project Consortium, Gene Expression Regulation, DNA-Binding Proteins/genetics/metabolism, RNA, Human genome, Immunization, Generic health relevance, Developmental Biology
Abstract

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome., National Human Genome Research Institute (U.S.), National Institutes of Health (U.S.)

Published
2011
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