Author: "Snyder, Michael P." / Journal: nature - Searchworks@Jio Institute Digital Library Search Results

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1. Temporal dynamics of the multi-omic response to endurance exercise training

Author: Bae, Dam, Dasari, Surendra, Dennis, Courtney, Evans, Charles R, Gaul, David A, Ilkayeva, Olga, Ivanova, Anna A, Kachman, Maureen T, Keshishian, Hasmik, Lanza, Ian R, Lira, Ana C, Muehlbauer, Michael J, Nair, Venugopalan D, Piehowski, Paul D, Rooney, Jessica L, Smith, Kevin S, Stowe, Cynthia L, Zhao, Bingqing, Clark, Natalie M, Jimenez-Morales, David, Lindholm, Malene E, Many, Gina M, Sanford, James A, Smith, Gregory R, Vetr, Nikolai G, Zhang, Tiantian, Almagro Armenteros, Jose J, Avila-Pacheco, Julian, Bararpour, Nasim, Ge, Yongchao, Hou, Zhenxin, Marwaha, Shruti, Presby, David M, Natarajan Raja, Archana, Savage, Evan M, Steep, Alec, Sun, Yifei, Wu, Si, Zhen, Jimmy, Bodine, Sue C, Esser, Karyn A, Goodyear, Laurie J, Schenk, Simon, Montgomery, Stephen B, Fernández, Facundo M, Sealfon, Stuart C, Snyder, Michael P, Adkins, Joshua N, Ashley, Euan, Burant, Charles F, Carr, Steven A, Clish, Clary B, Cutter, Gary, Gerszten, Robert E, Kraus, William E, Li, Jun Z, Miller, Michael E, Nair, K Sreekumaran, Newgard, Christopher, Ortlund, Eric A, Qian, Wei-Jun, Tracy, Russell, Walsh, Martin J, Wheeler, Matthew T, Dalton, Karen P, Hastie, Trevor, Hershman, Steven G, Samdarshi, Mihir, Teng, Christopher, Tibshirani, Rob, Cornell, Elaine, Gagne, Nicole, May, Sandy, Bouverat, Brian, Leeuwenburgh, Christiaan, Lu, Ching-ju, Pahor, Marco, Hsu, Fang-Chi, Rushing, Scott, Walkup, Michael P, Nicklas, Barbara, Rejeski, W Jack, Williams, John P, Xia, Ashley, Albertson, Brent G, Barton, Elisabeth R, Booth, Frank W, Caputo, Tiziana, Cicha, Michael, De Sousa, Luis Gustavo Oliveira, Farrar, Roger, Hevener, Andrea L, Hirshman, Michael F, Jackson, Bailey E, Ke, Benjamin G, Kramer, Kyle S, Lessard, Sarah J, Makarewicz, Nathan S, Marshall, Andrea G, and Nigro, Pasquale
Subjects: Health Sciences, Sports Science and Exercise, Prevention, Human Genome, Cardiovascular, Behavioral and Social Science, Genetics, Physical Activity, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Generic health relevance, Inflammatory and immune system, Good Health and Well Being, Animals, Female, Humans, Male, Rats, Acetylation, Blood, Cardiovascular Diseases, Databases, Factual, Endurance Training, Epigenome, Inflammatory Bowel Diseases, Internet, Lipidomics, Metabolome, Mitochondria, Multiomics, Non-alcoholic Fatty Liver Disease, Organ Specificity, Phosphorylation, Physical Conditioning, Animal, Physical Endurance, Proteome, Proteomics, Time Factors, Transcriptome, Ubiquitination, Wounds and Injuries, MoTrPAC Study Group, Lead Analysts, MoTrPAC Study Group, General Science & Technology
Abstract: Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).
Published: 2024

2. An exercise-inducible metabolite that suppresses feeding and obesity.

Author: Li, Veronica L, He, Yang, Contrepois, Kévin, Liu, Hailan, Kim, Joon T, Wiggenhorn, Amanda L, Tanzo, Julia T, Tung, Alan Sheng-Hwa, Lyu, Xuchao, Zushin, Peter-James H, Jansen, Robert S, Michael, Basil, Loh, Kang Yong, Yang, Andrew C, Carl, Christian S, Voldstedlund, Christian T, Wei, Wei, Terrell, Stephanie M, Moeller, Benjamin C, Arthur, Rick M, Wallis, Gareth A, van de Wetering, Koen, Stahl, Andreas, Kiens, Bente, Richter, Erik A, Banik, Steven M, Snyder, Michael P, Xu, Yong, and Long, Jonathan Z
Subjects: Animals, Mice, Diabetes Mellitus, Type 2, Obesity, Disease Models, Animal, Body Weight, Lactic Acid, Glucose, Phenylalanine, Physical Conditioning, Animal, Feeding Behavior, Energy Metabolism, Eating, Adiposity, Nutrition, Diabetes, Cardiovascular, Metabolic and endocrine, Cancer, Stroke, Oral and gastrointestinal, General Science & Technology
Abstract: Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1-5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanine occurs in CNDP2+ cells, including macrophages, monocytes and other immune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are also observed in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.
Published: 2022

3. Author Correction: Perspectives on ENCODE

Author: Snyder, Michael P, Gingeras, Thomas R, Moore, Jill E, Weng, Zhiping, Gerstein, Mark B, Ren, Bing, Hardison, Ross C, Stamatoyannopoulos, John A, Graveley, Brenton R, Feingold, Elise A, Pazin, Michael J, Pagan, Michael, Gilchrist, Daniel A, Hitz, Benjamin C, Cherry, J Michael, Bernstein, Bradley E, Mendenhall, Eric M, Zerbino, Daniel R, Frankish, Adam, Flicek, Paul, and Myers, Richard M
Subjects: ENCODE Project Consortium, General Science & Technology
Abstract: In this Article, the authors Rizi Ai (Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA) and Shantao Li (Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA) were mistakenly omitted from the ENCODE Project Consortium author list. The original Article has been corrected online.
Published: 2022

4. Author Correction: Expanded encyclopaedias of DNA elements in the human and mouse genomes

Author: Moore, Jill E, Purcaro, Michael J, Pratt, Henry E, Epstein, Charles B, Shoresh, Noam, Adrian, Jessika, Kawli, Trupti, Davis, Carrie A, Dobin, Alexander, Kaul, Rajinder, Halow, Jessica, Van Nostrand, Eric L, Freese, Peter, Gorkin, David U, Shen, Yin, He, Yupeng, Mackiewicz, Mark, Pauli-Behn, Florencia, Williams, Brian A, Mortazavi, Ali, Keller, Cheryl A, Zhang, Xiao-Ou, Elhajjajy, Shaimae I, Huey, Jack, Dickel, Diane E, Snetkova, Valentina, Wei, Xintao, Wang, Xiaofeng, Rivera-Mulia, Juan Carlos, Rozowsky, Joel, Zhang, Jing, Chhetri, Surya B, Zhang, Jialing, Victorsen, Alec, White, Kevin P, Visel, Axel, Yeo, Gene W, Burge, Christopher B, Lécuyer, Eric, Gilbert, David M, Dekker, Job, Rinn, John, Mendenhall, Eric M, Ecker, Joseph R, Kellis, Manolis, Klein, Robert J, Noble, William S, Kundaje, Anshul, Guigó, Roderic, Farnham, Peggy J, Cherry, J Michael, Myers, Richard M, Ren, Bing, Graveley, Brenton R, Gerstein, Mark B, Pennacchio, Len A, Snyder, Michael P, Bernstein, Bradley E, Wold, Barbara, Hardison, Ross C, Gingeras, Thomas R, Stamatoyannopoulos, John A, and Weng, Zhiping
Subjects: ENCODE Project Consortium, General Science & Technology
Abstract: In the version of this article initially published, two members of the ENCODE Project Consortium were missing from the author list. Rizi Ai (Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA) and Shantao Li (Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA) are now included in the author list. These errors have been corrected in the online version of the article.
Published: 2022

5. Perspectives on ENCODE

Author: Snyder, Michael P, Gingeras, Thomas R, Moore, Jill E, Weng, Zhiping, Gerstein, Mark B, Ren, Bing, Hardison, Ross C, Stamatoyannopoulos, John A, Graveley, Brenton R, Feingold, Elise A, Pazin, Michael J, Pagan, Michael, Gilchrist, Daniel A, Hitz, Benjamin C, Cherry, J Michael, Bernstein, Bradley E, Mendenhall, Eric M, Zerbino, Daniel R, Frankish, Adam, Flicek, Paul, and Myers, Richard M
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Biotechnology, Human Genome, 1.1 Normal biological development and functioning, Animals, Binding Sites, Chromatin, DNA Methylation, Databases, Genetic, Gene Expression Regulation, Genome, Genome, Human, Genomics, Histones, Humans, Mice, Molecular Sequence Annotation, Quality Control, Regulatory Sequences, Nucleic Acid, Transcription Factors, ENCODE Project Consortium, General Science & Technology
Abstract: The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression1. The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community.
Published: 2020

6. Expanded encyclopaedias of DNA elements in the human and mouse genomes

Author: Moore, Jill E, Purcaro, Michael J, Pratt, Henry E, Epstein, Charles B, Shoresh, Noam, Adrian, Jessika, Kawli, Trupti, Davis, Carrie A, Dobin, Alexander, Kaul, Rajinder, Halow, Jessica, Van Nostrand, Eric L, Freese, Peter, Gorkin, David U, Shen, Yin, He, Yupeng, Mackiewicz, Mark, Pauli-Behn, Florencia, Williams, Brian A, Mortazavi, Ali, Keller, Cheryl A, Zhang, Xiao-Ou, Elhajjajy, Shaimae I, Huey, Jack, Dickel, Diane E, Snetkova, Valentina, Wei, Xintao, Wang, Xiaofeng, Rivera-Mulia, Juan Carlos, Rozowsky, Joel, Zhang, Jing, Chhetri, Surya B, Zhang, Jialing, Victorsen, Alec, White, Kevin P, Visel, Axel, Yeo, Gene W, Burge, Christopher B, Lécuyer, Eric, Gilbert, David M, Dekker, Job, Rinn, John, Mendenhall, Eric M, Ecker, Joseph R, Kellis, Manolis, Klein, Robert J, Noble, William S, Kundaje, Anshul, Guigó, Roderic, Farnham, Peggy J, Cherry, J Michael, Myers, Richard M, Ren, Bing, Graveley, Brenton R, Gerstein, Mark B, Pennacchio, Len A, Snyder, Michael P, Bernstein, Bradley E, Wold, Barbara, Hardison, Ross C, Gingeras, Thomas R, Stamatoyannopoulos, John A, and Weng, Zhiping
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, 1.1 Normal biological development and functioning, Animals, Chromatin, DNA, DNA Footprinting, DNA Methylation, DNA Replication Timing, Databases, Genetic, Deoxyribonuclease I, Genome, Genome, Human, Genomics, Histones, Humans, Mice, Mice, Transgenic, Molecular Sequence Annotation, RNA-Binding Proteins, Registries, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Transposases, ENCODE Project Consortium, General Science & Technology
Abstract: The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.
Published: 2020

7. Expanded encyclopaedias of DNA elements in the human and mouse genomes.

Author: ENCODE Project Consortium, Moore, Jill E, Purcaro, Michael J, Pratt, Henry E, Epstein, Charles B, Shoresh, Noam, Adrian, Jessika, Kawli, Trupti, Davis, Carrie A, Dobin, Alexander, Kaul, Rajinder, Halow, Jessica, Van Nostrand, Eric L, Freese, Peter, Gorkin, David U, Shen, Yin, He, Yupeng, Mackiewicz, Mark, Pauli-Behn, Florencia, Williams, Brian A, Mortazavi, Ali, Keller, Cheryl A, Zhang, Xiao-Ou, Elhajjajy, Shaimae I, Huey, Jack, Dickel, Diane E, Snetkova, Valentina, Wei, Xintao, Wang, Xiaofeng, Rivera-Mulia, Juan Carlos, Rozowsky, Joel, Zhang, Jing, Chhetri, Surya B, Zhang, Jialing, Victorsen, Alec, White, Kevin P, Visel, Axel, Yeo, Gene W, Burge, Christopher B, Lécuyer, Eric, Gilbert, David M, Dekker, Job, Rinn, John, Mendenhall, Eric M, Ecker, Joseph R, Kellis, Manolis, Klein, Robert J, Noble, William S, Kundaje, Anshul, Guigó, Roderic, Farnham, Peggy J, Cherry, J Michael, Myers, Richard M, Ren, Bing, Graveley, Brenton R, Gerstein, Mark B, Pennacchio, Len A, Snyder, Michael P, Bernstein, Bradley E, Wold, Barbara, Hardison, Ross C, Gingeras, Thomas R, Stamatoyannopoulos, John A, and Weng, Zhiping
Subjects: ENCODE Project Consortium, Chromatin, Animals, Mice, Transgenic, Humans, Mice, Deoxyribonuclease I, Transposases, RNA-Binding Proteins, Histones, DNA, Registries, DNA Footprinting, Genomics, DNA Methylation, DNA Replication Timing, Transcription, Genetic, Regulatory Sequences, Nucleic Acid, Genome, Genome, Human, Databases, Genetic, Molecular Sequence Annotation, Human Genome, HIV/AIDS, Vaccine Related, Biotechnology, Genetics, Immunization, Vaccine Related (AIDS), Prevention, 1.1 Normal biological development and functioning, Generic health relevance, General Science & Technology
Abstract: The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.
Published: 2020

8. Perspectives on ENCODE.

Author: ENCODE Project Consortium, Snyder, Michael P, Gingeras, Thomas R, Moore, Jill E, Weng, Zhiping, Gerstein, Mark B, Ren, Bing, Hardison, Ross C, Stamatoyannopoulos, John A, Graveley, Brenton R, Feingold, Elise A, Pazin, Michael J, Pagan, Michael, Gilchrist, Daniel A, Hitz, Benjamin C, Cherry, J Michael, Bernstein, Bradley E, Mendenhall, Eric M, Zerbino, Daniel R, Frankish, Adam, Flicek, Paul, and Myers, Richard M
Subjects: ENCODE Project Consortium, Chromatin, Animals, Humans, Mice, Histones, Transcription Factors, Genomics, DNA Methylation, Gene Expression Regulation, Binding Sites, Regulatory Sequences, Nucleic Acid, Genome, Genome, Human, Quality Control, Databases, Genetic, Molecular Sequence Annotation, Human Genome, Vaccine Related, Biotechnology, Genetics, Immunization, Vaccine Related (AIDS), Prevention, 1.1 Normal biological development and functioning, Generic health relevance, General Science & Technology
Abstract: The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression1. The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community.
Published: 2020

9. Physiological blood–brain transport is impaired with age by a shift in transcytosis

Author: Yang, Andrew C, Stevens, Marc Y, Chen, Michelle B, Lee, Davis P, Stähli, Daniel, Gate, David, Contrepois, Kévin, Chen, Winnie, Iram, Tal, Zhang, Lichao, Vest, Ryan T, Chaney, Aisling, Lehallier, Benoit, Olsson, Niclas, du Bois, Haley, Hsieh, Ryan, Cropper, Haley C, Berdnik, Daniela, Li, Lulin, Wang, Elizabeth Y, Traber, Gavin M, Bertozzi, Carolyn R, Luo, Jian, Snyder, Michael P, Elias, Joshua E, Quake, Stephen R, James, Michelle L, and Wyss-Coray, Tony
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Neurosciences, Brain Disorders, Neurodegenerative, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Aging, Alkaline Phosphatase, Animals, Antibodies, Biological Transport, Blood Proteins, Blood-Brain Barrier, Brain, Drug Delivery Systems, Health, Humans, Male, Mice, Mice, Inbred C57BL, Plasma, Proteome, Receptors, Transferrin, Transcription, Genetic, Transcytosis, Transferrin, General Science & Technology
Abstract: The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1-3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery.
Published: 2020

10. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Author: Snyder, Michael P, Lin, Shin, Posgai, Amanda, Atkinson, Mark, Regev, Aviv, Rood, Jennifer, Rozenblatt-Rosen, Orit, Gaffney, Leslie, Hupalowska, Anna, Satija, Rahul, Gehlenborg, Nils, Shendure, Jay, Laskin, Julia, Harbury, Pehr, Nystrom, Nicholas A, Silverstein, Jonathan C, Bar-Joseph, Ziv, Zhang, Kun, Börner, Katy, Lin, Yiing, Conroy, Richard, Procaccini, Dena, Roy, Ananda L, Pillai, Ajay, Brown, Marishka, Galis, Zorina S, Cai, Long, Trapnell, Cole, Jackson, Dana, Nolan, Garry, Greenleaf, William James, Plevritis, Sylvia, Ahadi, Sara, Nevins, Stephanie A, Lee, Hayan, Schuerch, Christian Martijn, Black, Sarah, Venkataraaman, Vishal Gautham, Esplin, Ed, Horning, Aaron, Bahmani, Amir, Sun, Xin, Jain, Sanjay, Hagood, James, Pryhuber, Gloria, Kharchenko, Peter, Bodenmiller, Bernd, Brusko, Todd, Clare-Salzler, Michael, Nick, Harry, Otto, Kevin, Wasserfall, Clive, Jorgensen, Marda, Brusko, Maigan, Maffioletti, Sergio, Caprioli, Richard M, Spraggins, Jeffrey M, Gutierrez, Danielle, Patterson, Nathan Heath, Neumann, Elizabeth K, Harris, Raymond, deCaestecker, Mark, Fogo, Agnes B, van de Plas, Raf, Lau, Ken, Yuan, Guo-Cheng, Zhu, Qian, Dries, Ruben, Yin, Peng, Saka, Sinem K, Kishi, Jocelyn Y, Wang, Yu, Goldaracena, Isabel, Ye, DongHye, Burnum-Johnson, Kristin E, Piehowski, Paul D, Ansong, Charles, Zhu, Ying, Desai, Tushar, Mulye, Jay, Chou, Peter, Nagendran, Monica, Teichmann, Sarah A, Paten, Benedict, Murphy, Robert F, Ma, Jian, Kiselev, Vladimir Yu, Kingsford, Carl, and Ricarte, Allyson
Subjects: Human Genome, Genetics, Networking and Information Technology R&D, Bioengineering, Aging, Atlases as Topic, Biomedical Research, Female, Health, Humans, International Cooperation, Male, Models, Anatomic, Molecular Biology, National Institutes of Health (U.S.), Organ Specificity, Single-Cell Analysis, United States, q-bio.OT, General Science & Technology
Abstract: Transformative technologies are enabling the construction of threedimensional (3D) maps of tissues with unprecedented spatial and molecularresolution. Over the next seven years, the NIH Common Fund Human BiomolecularAtlas Program (HuBMAP) intends to develop a widely accessible framework forcomprehensively mapping the human body at single-cell resolution by supportingtechnology development, data acquisition, and detailed spatial mapping. HuBMAPwill integrate its efforts with other funding agencies, programs, consortia,and the biomedical research community at large towards the shared vision of acomprehensive, accessible 3D molecular and cellular atlas of the human body, inhealth and various disease settings.
Published: 2019

11. Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy.

Author: Lee, Jaecheol, Termglinchan, Vittavat, Diecke, Sebastian, Itzhaki, Ilanit, Lam, Chi Keung, Garg, Priyanka, Lau, Edward, Greenhaw, Matthew, Seeger, Timon, Wu, Haodi, Zhang, Joe Z, Chen, Xingqi, Gil, Isaac Perea, Ameen, Mohamed, Sallam, Karim, Rhee, June-Wha, Churko, Jared M, Chaudhary, Rinkal, Chour, Tony, Wang, Paul J, Snyder, Michael P, Chang, Howard Y, Karakikes, Ioannis, and Wu, Joseph C
Subjects: Cells, Cultured, Chromatin, Myocytes, Cardiac, Humans, Cardiomyopathy, Dilated, Calcium, Receptor, Platelet-Derived Growth Factor beta, Platelet-Derived Growth Factor, Lamin Type A, RNA, Messenger, Signal Transduction, Chromatin Assembly and Disassembly, Homeostasis, Mutation, Models, Biological, Arrhythmias, Cardiac, Induced Pluripotent Stem Cells, Haploinsufficiency, Single-Cell Analysis, Nonsense Mediated mRNA Decay, In Vitro Techniques, Arrhythmias, Cardiac, Cardiomyopathy, Dilated, Cells, Cultured, Models, Biological, Myocytes, RNA, Messenger, Receptor, Platelet-Derived Growth Factor beta, General Science & Technology
Abstract: Lamin A/C (LMNA) is one of the most frequently mutated genes associated with dilated cardiomyopathy (DCM). DCM related to mutations in LMNA is a common inherited cardiomyopathy that is associated with systolic dysfunction and cardiac arrhythmias. Here we modelled the LMNA-related DCM in vitro using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Electrophysiological studies showed that the mutant iPSC-CMs displayed aberrant calcium homeostasis that led to arrhythmias at the single-cell level. Mechanistically, we show that the platelet-derived growth factor (PDGF) signalling pathway is activated in mutant iPSC-CMs compared to isogenic control iPSC-CMs. Conversely, pharmacological and molecular inhibition of the PDGF signalling pathway ameliorated the arrhythmic phenotypes of mutant iPSC-CMs in vitro. Taken together, our findings suggest that the activation of the PDGF pathway contributes to the pathogenesis of LMNA-related DCM and point to PDGF receptor-β (PDGFRB) as a potential therapeutic target.
Published: 2019

12. Longitudinal multi-omics of host-microbe dynamics in prediabetes.

Author: Zhou, Wenyu, Sailani, M Reza, Contrepois, Kévin, Zhou, Yanjiao, Ahadi, Sara, Leopold, Shana R, Zhang, Martin J, Rao, Varsha, Avina, Monika, Mishra, Tejaswini, Johnson, Jethro, Lee-McMullen, Brittany, Chen, Songjie, Metwally, Ahmed A, Tran, Thi Dong Binh, Nguyen, Hoan, Zhou, Xin, Albright, Brandon, Hong, Bo-Young, Petersen, Lauren, Bautista, Eddy, Hanson, Blake, Chen, Lei, Spakowicz, Daniel, Bahmani, Amir, Salins, Denis, Leopold, Benjamin, Ashland, Melanie, Dagan-Rosenfeld, Orit, Rego, Shannon, Limcaoco, Patricia, Colbert, Elizabeth, Allister, Candice, Perelman, Dalia, Craig, Colleen, Wei, Eric, Chaib, Hassan, Hornburg, Daniel, Dunn, Jessilyn, Liang, Liang, Rose, Sophia Miryam Schüssler-Fiorenza, Kukurba, Kim, Piening, Brian, Rost, Hannes, Tse, David, McLaughlin, Tracey, Sodergren, Erica, Weinstock, George M, and Snyder, Michael
Subjects: Humans, Respiratory Tract Infections, Diabetes Mellitus, Type 2, Prediabetic State, Insulin Resistance, Inflammation, Insulin, Glucose, Proteome, Influenza Vaccines, Anti-Bacterial Agents, Vaccination, Cohort Studies, Longitudinal Studies, Computational Biology, Adult, Aged, Middle Aged, Female, Male, Stress, Physiological, Transcriptome, Healthy Volunteers, Microbiota, Datasets as Topic, Biomarkers, Gastrointestinal Microbiome, Host Microbial Interactions, Diabetes Mellitus, Type 2, Stress, Physiological, General Science & Technology
Abstract: Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.
Published: 2019

13. Comparative analysis of regulatory information and circuits across distant species

Author: Boyle, Alan P, Araya, Carlos L, Brdlik, Cathleen, Cayting, Philip, Cheng, Chao, Cheng, Yong, Gardner, Kathryn, Hillier, LaDeana W, Janette, Judith, Jiang, Lixia, Kasper, Dionna, Kawli, Trupti, Kheradpour, Pouya, Kundaje, Anshul, Li, Jingyi Jessica, Ma, Lijia, Niu, Wei, Rehm, E Jay, Rozowsky, Joel, Slattery, Matthew, Spokony, Rebecca, Terrell, Robert, Vafeados, Dionne, Wang, Daifeng, Weisdepp, Peter, Wu, Yi-Chieh, Xie, Dan, Yan, Koon-Kiu, Feingold, Elise A, Good, Peter J, Pazin, Michael J, Huang, Haiyan, Bickel, Peter J, Brenner, Steven E, Reinke, Valerie, Waterston, Robert H, Gerstein, Mark, White, Kevin P, Kellis, Manolis, and Snyder, Michael
Subjects: Human Genome, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Animals, Binding Sites, Caenorhabditis elegans, Chromatin Immunoprecipitation, Conserved Sequence, Drosophila melanogaster, Evolution, Molecular, Gene Expression Regulation, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Genome, Humans, Molecular Sequence Annotation, Nucleotide Motifs, Organ Specificity, Transcription Factors, General Science & Technology
Abstract: Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1,019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regulatory networks are remarkably conserved and that orthologous regulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual network connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regulatory underpinnings of model organism biology and how these relate to human biology, development and disease.
Published: 2014

14. Landscape and variation of RNA secondary structure across the human transcriptome

Author: Wan, Yue, Qu, Kun, Zhang, Qiangfeng Cliff, Flynn, Ryan A, Manor, Ohad, Ouyang, Zhengqing, Zhang, Jiajing, Spitale, Robert C, Snyder, Michael P, Segal, Eran, and Chang, Howard Y
Subjects: Genetics, Human Genome, 3' Untranslated Regions, Base Sequence, Binding Sites, Child, Female, Gene Expression Regulation, Genome, Human, Humans, Male, MicroRNAs, Nucleic Acid Conformation, Open Reading Frames, Point Mutation, RNA, RNA Splice Sites, RNA-Binding Proteins, Transcriptome, General Science & Technology
Abstract: In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic microRNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of 'riboSNitches' versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3' untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.
Published: 2014

15. Mapping copy number variation by population-scale genome sequencing.

Author: Mills, Ryan, Walter, Klaudia, Stewart, Chip, Handsaker, Robert, Chen, Ken, Alkan, Can, Abyzov, Alexej, Yoon, Seungtai, Ye, Kai, Cheetham, R, Chinwalla, Asif, Conrad, Donald, Fu, Yutao, Grubert, Fabian, Hajirasouliha, Iman, Hormozdiari, Fereydoun, Iakoucheva, Lilia, Iqbal, Zamin, Kang, Shuli, Kidd, Jeffrey, Konkel, Miriam, Korn, Joshua, Khurana, Ekta, Kural, Deniz, Lam, Hugo, Leng, Jing, Li, Ruiqiang, Li, Yingrui, Lin, Chang-Yun, Luo, Ruibang, Mu, Xinmeng, Nemesh, James, Peckham, Heather, Rausch, Tobias, Scally, Aylwyn, Shi, Xinghua, Stromberg, Michael, Stütz, Adrian, Urban, Alexander, Walker, Jerilyn, Wu, Jiantao, Zhang, Yujun, Zhang, Zhengdong, Batzer, Mark, Ding, Li, Marth, Gabor, McVean, Gil, Sebat, Jonathan, Snyder, Michael, Wang, Jun, Ye, Kenny, Eichler, Evan, Gerstein, Mark, Hurles, Matthew, Lee, Charles, McCarroll, Steven, and Korbel, Jan
Subjects: DNA Copy Number Variations, Gene Duplication, Genetic Predisposition to Disease, Genetics, Population, Genome, Human, Genomics, Genotype, Humans, Mutagenesis, Insertional, Reproducibility of Results, Sequence Analysis, DNA, Sequence Deletion
Abstract: Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.
Published: 2011

16. The impact of rare variation on gene expression across tissues

Author: Li, Xin, Kim, Yungil, Tsang, Emily K., Davis, Joe R., Damani, Farhan N., Chiang, Colby, Hess, Gaelen T., Zappala, Zachary, Strober, Benjamin J., Scott, Alexandra J., Li, Amy, Ganna, Andrea, Bassik, Michael C., Merker, Jason D., Aguet, Franois, 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., Segr, 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., Conrad, Donald F., Cox, Nancy J., Delaneau, Olivier, Dermitzakis, Emmanouil T., Engelhardt, Barbara E., Eskin, Eleazar, Ferreira, Pedro G., Frsard, Laure, Gamazon, Eric R., Garrido-Martn, Diego, Gewirtz, Ariel D.H., Gliner, Genna, Gloudemans, Michael J., Guigo, Roderic, Hall, Ira M., Han, Buhm, He, Yuan, Hormozdiari, Farhad, Howald, Cedric, Kyung Im, Hae, Jo, Brian, Yong Kang, Eun, Kim-Hellmuth, Sarah, Lappalainen, Tuuli, Li, Gen, Liu, Boxiang, Mangul, Serghei, McCarthy, Mark I., McDowell, Ian C., Mohammadi, Pejman, Monlong, Jean, Montgomery, Stephen B., Muoz-Aguirre, Manuel, Ndungu, Anne W., Nicolae, Dan L., 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, Shabalin, Andrey A., Sodaei, Reza, Stephens, Matthew, Stranger, Barbara E., Sul, Jae Hoon, Urbut, Sarah, van de Bunt, Martijn, Wang, Gao, Wen, Xiaoquan, Wright, Fred A., Xi, Hualin S., Yeger-Lotem, Esti, 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, Billy Li, Jin, 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, and Zhu, Jingchun
Subjects: Disease susceptibility -- Genetic aspects, Genetic variation -- Observations, Gene expression -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): Xin Li [1]; Yungil Kim [2]; Emily K. Tsang [1, 3]; Joe R. Davis [1, 4]; Farhan N. Damani [2]; Colby Chiang [5]; Gaelen T. Hess [4]; Zachary Zappala [...]
Published: 2017
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17. Dynamic landscape and regulation of RNA editing in mammals

Author: Tan, Meng How, Li, Qin, Shanmugam, Raghuvaran, Piskol, Robert, Kohler, Jennefer, Young, Amy N., Liu, Kaiwen Ivy, Zhang, Rui, Ramaswami, Gokul, Ariyoshi, Kentaro, Gupte, Ankita, Keegan, Liam P., George, Cyril X., Ramu, Avinash, Huang, Ni, Pollina, Elizabeth A., Leeman, Dena S., Rustighi, Alessandra, Goh, Y. P. Sharon, Aguet, Franois, 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., Segr, 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., Cox, Nancy J., Damani, Farhan N., Davis, Joe R., Delaneau, Olivier, Dermitzakis, Emmanouil T., Engelhardt, Barbara E., Eskin, Eleazar, Ferreira, Pedro G., Frsard, Laure, Gamazon, Eric R., Garrido-Martn, Diego, Gewirtz, Ariel D. H., Gliner, Genna, Gloudemans, Michael J., Guigo, Roderic, Hall, Ira M., Han, Buhm, He, Yuan, Hormozdiari, Farhad, Howald, Cedric, Kyung Im, Hae, Jo, Brian, Yong Kang, Eun, 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., Muoz-Aguirre, Manuel, Ndungu, Anne W., Nicolae, Dan L., 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, 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, 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, Chawla, Ajay, Del Sal, Giannino, Peltz, Gary, Brunet, Anne, Samuel, Charles E., OConnell, Mary A., Walkley, Carl R., and Nishikura, Kazuko
Subjects: Genetic research, Mammals -- Genetic aspects, RNA processing -- Research, Genetic regulation, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): Meng How Tan (corresponding author) [1, 2, 3]; Qin Li [1]; Raghuvaran Shanmugam [2, 3]; Robert Piskol [1]; Jennefer Kohler [1]; Amy N. Young [1]; Kaiwen Ivy Liu [3]; [...]
Published: 2017
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18. Landscape of X chromosome inactivation across human tissues

Author: Tukiainen, Taru, Villani, Alexandra-Chlo, Yen, Angela, Rivas, Manuel A., Marshall, Jamie L., Satija, Rahul, Aguirre, Matt, Gauthier, Laura, Fleharty, Mark, Kirby, Andrew, Cummings, Beryl B., Castel, Stephane E., Karczewski, Konrad J., Aguet, Franois, Byrnes, Andrea, Ardlie, Kristin G., Gelfand, Ellen T., Getz, Gad, Hadley, Kane, Handsaker, Robert E., Huang, Katherine H., Kashin, Seva, Lek, Monkol, Li, Xiao, MacArthur, Daniel G., Nedzel, Jared L., Nguyen, Duyen T., Noble, Michael S., Segr, Ayellet V., Trowbridge, Casandra A., Abell, Nathan S., Balliu, Brunilda, Barshir, Ruth, Basha, Omer, Battle, Alexis, Bogu, Gireesh K., Brown, Andrew, Brown, Christopher D., Chen, Lin S., Chiang, Colby, Conrad, Donald F., Cox, Nancy J., Damani, Farhan N., Davis, Joe R., Delaneau, Olivier, Dermitzakis, Emmanouil T., Engelhardt, Barbara E., Eskin, Eleazar, Ferreira, Pedro G., Frsard, Laure, Gamazon, Eric R., Garrido-Martn, Diego, Gewirtz, Ariel D. H., Gliner, Genna, Gloudemans, Michael J., Guigo, Roderic, Hall, Ira M., Han, Buhm, He, Yuan, Hormozdiari, Farhad, Howald, Cedric, Kyung Im, Hae, Jo, Brian, Yong Kang, Eun, 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., Muoz-Aguirre, Manuel, Ndungu, Anne W., Nicolae, Dan L., 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, Regev, Aviv, and Hacohen, Nir
Subjects: Chromosomes -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): Taru Tukiainen (corresponding author) [1, 2]; Alexandra-Chlo Villani [2, 3]; Angela Yen [2, 4]; Manuel A. Rivas [1, 2, 5]; Jamie L. Marshall [1, 2]; Rahul Satija [2, 6, [...]
Published: 2017
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19. Recurrent repeat expansions in human cancer genomes

Author: Erwin, Graham S., primary, Gürsoy, Gamze, additional, Al-Abri, Rashid, additional, Suriyaprakash, Ashwini, additional, Dolzhenko, Egor, additional, Zhu, Kevin, additional, Hoerner, Christian R., additional, White, Shannon M., additional, Ramirez, Lucia, additional, Vadlakonda, Ananya, additional, Vadlakonda, Alekhya, additional, von Kraut, Konor, additional, Park, Julia, additional, Brannon, Charlotte M., additional, Sumano, Daniel A., additional, Kirtikar, Raushun A., additional, Erwin, Alicia A., additional, Metzner, Thomas J., additional, Yuen, Ryan K. C., additional, Fan, Alice C., additional, Leppert, John T., additional, Eberle, Michael A., additional, Gerstein, Mark, additional, and Snyder, Michael P., additional
Published: 2022
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20. Genetic effects on gene expression across human tissues

Author: 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., Cox, Nancy J., 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, Im, Hae Kyung, 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., Nicolae, Dan L., 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, Roger A., 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, James W., Lee, Christopher M., Paten, Benedict, Rosenbloom, Kate R., Vivian, John, Zhu, Jingchun, Brown, Andrew A., Nguyen, Duyen Y., Sullivan, Timothy J., Addington, Anjene, Koester, Susan, Lockhart, Nicole C., Roe, Bryan, Valley, Dana, Gewirtz, Ariel D. H., He, Amy Z., Quon, Gerald, Ripke, Stephan, Shimko, Tyler C., Teran, Nicole A., Zhang, Hailei, Bustamante, Carlos D., and Guigó, Roderic
Published: 2017
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21. Single-cell chromatin accessibility reveals principles of regulatory variation

Author: Buenrostro, Jason D., Wu, Beijing, Litzenburger, Ulrike M., Ruff, Dave, Gonzales, Michael L., Snyder, Michael P., Chang, Howard Y., and Greenleaf, William J.
Subjects: Cell regulation -- Research, Chromatin -- Physiological aspects, Cytological research, Genomics -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Cell-to-cell variation is a universal feature of life that affects a wide range of biological phenomena, from developmental plasticity (1,2) to tumour heterogeneity (3). Although recent advances have improved our ability to document cellular phenotypic variation (4-8), the fundamental mechanisms that generate variability from identical DNA sequences remain elusive. Here we reveal the landscape and principles of mammalian DNA regulatory variation by developing a robust method for mapping the accessible genome of individual cells by assay for transposase-accessible chromatin using sequencing (ATAC-seq) (9) integrated into a programmable microfluidics platform. Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation. Accessibility variance is systematically associated with specific trans-factors and cis-elements, and we discover combinations of trans-factors associated with either induction or suppression of cell-to-cell variability. We further identify sets of trans-factors associated with cell-type-specific accessibility variance across eight cell types. Targeted perturbations of cell cycle or transcription factor signalling evoke stimulus-specific changes in this observed variability. The pattern of accessibility variation in cis across the genome recapitulates chromosome compartments (10) denovo, linking single-cell accessibility variation to three-dimensional genome organization. Single-cell analysis of DNA accessibility provides new insight into cellular variation of the 'regulome'., Heterogeneity within cellular populations has been evident since the first microscopic observations of individual cells. Recent proliferation of powerful methods for interrogating single cells (4-8) has allowed detailed characterization of [...]
Published: 2015

22. Organization of the human intestine at single-cell resolution

Author: Hickey, John W., Becker, Winston R., Nevins, Stephanie A., Horning, Aaron, Perez, Almudena Espin, Zhu, Chenchen, Zhu, Bokai, Wei, Bei, Chiu, Roxanne, Chen, Derek C., Cotter, Daniel L., Esplin, Edward D., Weimer, Annika K., Caraccio, Chiara, Venkataraaman, Vishal, Schürch, Christian M., Black, Sarah, Brbić, Maria, Cao, Kaidi, Chen, Shuxiao, Zhang, Weiruo, Monte, Emma, Zhang, Nancy R., Ma, Zongming, Leskovec, Jure, Zhang, Zhengyan, Lin, Shin, Longacre, Teri, Plevritis, Sylvia K., Lin, Yiing, Nolan, Garry P., Greenleaf, William J., and Snyder, Michael
Abstract: The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.
Published: 2023
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23. Topologically associating domains are stable units of replication-timing regulation

Author: Pope, Benjamin D., Ryba, Tyrone, Dileep, Vishnu, Yue, Feng, Wu, Weisheng, Denas, Olgert, Vera, Daniel L., Wang, Yanli, Hansen, R. Scott, Canfield, Theresa K., Thurman, Robert E., Cheng, Yong, Gulsoy, Gunhan, Dennis, Jonathan H., Snyder, Michael P., Stamatoyannopoulos, John A., Taylor, James, Hardison, Ross C., Kahveci, Tamer, Ren, Bing, and Gilbert, David M.
Subjects: Genetic research, Genetic regulation -- Research, Chromosome replication -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): Benjamin D. Pope [1]; Tyrone Ryba [2]; Vishnu Dileep [1]; Feng Yue [3, 4]; Weisheng Wu [5]; Olgert Denas [6]; Daniel L. Vera [1]; Yanli Wang [4]; R. Scott [...]
Published: 2014
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24. A comparative encyclopedia of DNA elements in the mouse genome

Author: Yue, Feng, Cheng, Yong, Breschi, Alessandra, Vierstra, Jeff, Wu, Weisheng, Ryba, Tyrone, Sandstrom, Richard, Ma, Zhihai, Davis, Carrie, Pope, Benjamin D., Shen, Yin, Pervouchine, Dmitri D., Djebali, Sarah, Thurman, Robert E., Kaul, Rajinder, Rynes, Eric, Kirilusha, Anthony, Marinov, Georgi K., Williams, Brian A., Trout, Diane, Amrhein, Henry, Fisher-Aylor, Katherine, Antoshechkin, Igor, DeSalvo, Gilberto, See, Lei-Hoon, Fastuca, Meagan, Drenkow, Jorg, Zaleski, Chris, Dobin, Alex, Prieto, Pablo, Lagarde, Julien, Bussotti, Giovanni, Tanzer, Andrea, Denas, Olgert, Li, Kanwei, Bender, M. A., Zhang, Miaohua, Byron, Rachel, Groudine, Mark T., McCleary, David, Pham, Long, Ye, Zhen, Kuan, Samantha, Edsall, Lee, Wu, Yi-Chieh, Rasmussen, Matthew D., Bansal, Mukul S., Kellis, Manolis, Keller, Cheryl A., Morrissey, Christapher S., Mishra, Tejaswini, Jain, Deepti, Dogan, Nergiz, Harris, Robert S., Cayting, Philip, Kawli, Trupti, Boyle, Alan P., Euskirchen, Ghia, Kundaje, Anshul, Lin, Shin, Lin, Yiing, Jansen, Camden, Malladi, Venkat S., Cline, Melissa S., Erickson, Drew T., Kirkup, Vanessa M., Learned, Katrina, Sloan, Cricket A., Rosenbloom, Kate R., Lacerda de Sousa, Beatriz, Beal, Kathryn, Pignatelli, Miguel, Flicek, Paul, Lian, Jin, Kahveci, Tamer, Lee, Dongwon, James Kent, W., Ramalho Santos, Miguel, Herrero, Javier, Notredame, Cedric, Johnson, Audra, Vong, Shinny, Lee, Kristen, Bates, Daniel, Neri, Fidencio, Diegel, Morgan, Canfield, Theresa, Sabo, Peter J., Wilken, Matthew S., Reh, Thomas A., Giste, Erika, Shafer, Anthony, Kutyavin, Tanya, Haugen, Eric, Dunn, Douglas, Reynolds, Alex P., Neph, Shane, Humbert, Richard, Scott Hansen, R., De Bruijn, Marella, Selleri, Licia, Rudensky, Alexander, Josefowicz, Steven, Samstein, Robert, Eichler, Evan E., Orkin, Stuart H., Levasseur, Dana, Papayannopoulou, Thalia, Chang, Kai-Hsin, Skoultchi, Arthur, Gosh, Srikanta, Disteche, Christine, Treuting, Piper, Wang, Yanli, Weiss, Mitchell J., Blobel, Gerd A., Cao, Xiaoyi, Zhong, Sheng, Wang, Ting, Good, Peter J., Lowdon, Rebecca F., Adams, Leslie B., Zhou, Xiao-Qiao, Pazin, Michael J., Feingold, Elise A., Wold, Barbara, Taylor, James, Mortazavi, Ali, Weissman, Sherman M., Stamatoyannopoulos, John A., Snyder, Michael P., Guigo, Roderic, Gingeras, Thomas R., Gilbert, David M., Hardison, Ross C., Beer, Michael A., and Ren, Bing
Subjects: Man -- Genetic aspects, Genetic research, Human beings -- Genetic aspects, Genomes -- Comparative analysis, Mice -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases., Author(s): Feng Yue [1, 2]; Yong Cheng [3]; Alessandra Breschi [4]; Jeff Vierstra [5]; Weisheng Wu [6]; Tyrone Ryba [7]; Richard Sandstrom [5]; Zhihai Ma [3]; Carrie Davis [8]; Benjamin [...]
Published: 2014
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25. Principles of regulatory information conservation between mouse and human

Author: Cheng, Yong, Ma, Zhihai, Kim, Bong-Hyun, Wu, Weisheng, Cayting, Philip, Boyle, Alan P., Sundaram, Vasavi, Xing, Xiaoyun, Dogan, Nergiz, Li, Jingjing, Euskirchen, Ghia, Lin, Shin, Lin, Yiing, Visel, Axel, Kawli, Trupti, Yang, Xinqiong, Patacsil, Dorrelyn, Keller, Cheryl A., Giardine, Belinda, Kundaje, Anshul, Wang, Ting, Pennacchio, Len A., Weng, Zhiping, Hardison, Ross C., and Snyder, Michael P.
Subjects: Man -- Natural history -- Genetic aspects, Human beings -- Natural history -- Genetic aspects, Genetic regulation -- Research, Transcription factors -- Research, Mice -- Natural history -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: To broaden our understanding of the evolution of gene regulation mechanisms, we generated occupancy profiles for 34 orthologous transcription factors (TFs) in human-mouse erythroid progenitor, lymphoblast and embryonic stem-cell lines. By combining the genome-wide transcription factor occupancy repertoires, associated epigenetic signals, and co-association patterns, here we deduce several evolutionary principles of gene regulatory features operating since the mouse and human lineages diverged. The genomic distribution profiles, primary binding motifs, chromatin states, and DNA methylation preferences are well conserved for TF-occupied sequences. However, the extent to which orthologous DNA segments are bound by orthologous TFs varies both among TFs and with genomic location: binding at promoters is more highly conserved than binding at distal elements. Notably, occupancy-conserved TF-occupied sequences tend to be pleiotropic; they function in several tissues and also co-associate with many TFs. Single nucleotide variants at sites with potential regulatory functions are enriched in occupancy-conserved TF-occupied sequences., Author(s): Yong Cheng [1]; Zhihai Ma [1]; Bong-Hyun Kim [2]; Weisheng Wu [3, 4]; Philip Cayting [1]; Alan P. Boyle [1]; Vasavi Sundaram [5]; Xiaoyun Xing [5]; Nergiz Dogan [3]; [...]
Published: 2014
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26. Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

Author: Yan, Kelley S., Janda, Claudia Y., Chang, Junlei, Zheng, Grace X. Y., Larkin, Kathryn A., Luca, Vincent C., Chia, Luis A., Mah, Amanda T., Han, Arnold, Terry, Jessica M., Ootani, Akifumi, Roelf, Kelly, Lee, Mark, Yuan, Jenny, Li, Xiao, Bolen, Christopher R., Wilhelmy, Julie, Davies, Paige S., Ueno, Hiroo, von Furstenberg, Richard J., Belgrader, Phillip, Ziraldo, Solongo B., Ordonez, Heather, Henning, Susan J., Wong, Melissa H., Snyder, Michael P., Weissman, Irving L., Hsueh, Aaron J., Mikkelsen, Tarjei S., Garcia, K. Christopher, and Kuo, Calvin J.
Subjects: Ligands (Biochemistry) -- Health aspects, Stem cells -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract: Author(s): Kelley S. Yan [1, 2]; Claudia Y. Janda [3]; Junlei Chang [1]; Grace X. Y. Zheng [4]; Kathryn A. Larkin [1]; Vincent C. Luca [3]; Luis A. Chia [1]; [...]
Published: 2017
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27. Transcriptome variation in human tissues revealed by long-read sequencing

Author: Glinos, Dafni A., Garborcauskas, Garrett, Hoffman, Paul, Ehsan, Nava, Jiang, Lihua, Gokden, Alper, Dai, Xiaoguang, Aguet, François, Brown, Kathleen L., Garimella, Kiran, Bowers, Tera, Costello, Maura, Ardlie, Kristin, Jian, Ruiqi, Tucker, Nathan R., Ellinor, Patrick T., Harrington, Eoghan D., Tang, Hua, Snyder, Michael, Juul, Sissel, Mohammadi, Pejman, MacArthur, Daniel G., Lappalainen, Tuuli, and Cummings, Beryl B.
Abstract: Regulation of transcript structure generates transcript diversity and plays an important role in human disease1–7. The advent of long-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure8–16. In this Article, we present a large human long-read RNA-seq dataset using the Oxford Nanopore Technologies platform from 88 samples from Genotype-Tissue Expression (GTEx) tissues and cell lines, complementing the GTEx resource. We identified just over 70,000 novel transcripts for annotated genes, and validated the protein expression of 10% of novel transcripts. We developed a new computational package, LORALS, to analyse the genetic effects of rare and common variants on the transcriptome by allele-specific analysis of long reads. We characterized allele-specific expression and transcript structure events, providing new insights into the specific transcript alterations caused by common and rare genetic variants and highlighting the resolution gained from long-read data. We were able to perturb the transcript structure upon knockdown of PTBP1, an RNA binding protein that mediates splicing, thereby finding genetic regulatory effects that are modified by the cellular environment. Finally, we used this dataset to enhance variant interpretation and study rare variants leading to aberrant splicing patterns.
Published: 2022
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28. Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing

Author: Mahmoudi, Salah, primary, Mancini, Elena, additional, Xu, Lucy, additional, Moore, Alessandra, additional, Jahanbani, Fereshteh, additional, Hebestreit, Katja, additional, Srinivasan, Rajini, additional, Li, Xiyan, additional, Devarajan, Keerthana, additional, Prélot, Laurie, additional, Ang, Cheen Euong, additional, Shibuya, Yohei, additional, Benayoun, Bérénice A., additional, Chang, Anne Lynn S., additional, Wernig, Marius, additional, Wysocka, Joanna, additional, Longaker, Michael T., additional, Snyder, Michael P., additional, and Brunet, Anne, additional
Published: 2019
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29. Landscape of cohesin-mediated chromatin loops in the human genome

Author: Grubert, Fabian, Srivas, Rohith, Spacek, Damek V, Kasowski, Maya, Ruiz-Velasco, Mariana, Sinnott-Armstrong, Nasa, Greenside, Peyton, Narasimha, Anil, Liu, Qing, Geller, Benjamin, Sanghi, Akshay, Kulik, Michael, Sa, Silin, Rabinovitch, Marlene, Kundaje, Anshul, Dalton, Stephen, Zaugg, Judith B., and Snyder, Michael
Abstract: Physical interactions between distal regulatory elements have a key role in regulating gene expression, but the extent to which these interactions vary between cell types and contribute to cell-type-specific gene expression remains unclear. Here, to address these questions as part of phase III of the Encyclopedia of DNA Elements (ENCODE), we mapped cohesin-mediated chromatin loops, using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), and analysed gene expression in 24 diverse human cell types, including core ENCODE cell lines. Twenty-eight per cent of all chromatin loops vary across cell types; these variations modestly correlate with changes in gene expression and are effective at grouping cell types according to their tissue of origin. The connectivity of genes corresponds to different functional classes, with housekeeping genes having few contacts, and dosage-sensitive genes being more connected to enhancer elements. This atlas of chromatin loops complements the diverse maps of regulatory architecture that comprise the ENCODE Encyclopedia, and will help to support emerging analyses of genome structure and function.
Published: 2020
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30. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program.

Author: HuBMAP Consortium, Writing Group, Snyder, Michael P., Lin, Shin, Posgai, Amanda, Atkinson, Mark, Regev, Aviv, Rood, Jennifer, Rozenblatt-Rosen, Orit, Gaffney, Leslie, Hupalowska, Anna, Satija, Rahul, Gehlenborg, Nils, Shendure, Jay, Laskin, Julia, Harbury, Pehr, Nystrom, Nicholas A., Silverstein, Jonathan C., Bar-Joseph, Ziv, and Zhang, Kun
Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions. HuBMAP supports technology development, data acquisition, and spatial analyses to generate comprehensive molecular and cellular three-dimensional tissue maps. [ABSTRACT FROM AUTHOR]
Published: 2019
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31. Activation of PDGF pathway links LMNAmutation to dilated cardiomyopathy

Author: Lee, Jaecheol, Termglinchan, Vittavat, Diecke, Sebastian, Itzhaki, Ilanit, Lam, Chi, Garg, Priyanka, Lau, Edward, Greenhaw, Matthew, Seeger, Timon, Wu, Haodi, Zhang, Joe, Chen, Xingqi, Gil, Isaac, Ameen, Mohamed, Sallam, Karim, Rhee, June-Wha, Churko, Jared M., Chaudhary, Rinkal, Chour, Tony, Wang, Paul, Snyder, Michael, Chang, Howard, Karakikes, Ioannis, and Wu, Joseph
Abstract: Lamin A/C (LMNA) is one of the most frequently mutated genes associated with dilated cardiomyopathy (DCM). DCM related to mutations in LMNAis a common inherited cardiomyopathy that is associated with systolic dysfunction and cardiac arrhythmias. Here we modelled the LMNA-related DCM in vitro using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Electrophysiological studies showed that the mutant iPSC-CMs displayed aberrant calcium homeostasis that led to arrhythmias at the single-cell level. Mechanistically, we show that the platelet-derived growth factor (PDGF) signalling pathway is activated in mutant iPSC-CMs compared to isogenic control iPSC-CMs. Conversely, pharmacological and molecular inhibition of the PDGF signalling pathway ameliorated the arrhythmic phenotypes of mutant iPSC-CMs in vitro. Taken together, our findings suggest that the activation of the PDGF pathway contributes to the pathogenesis of LMNA-related DCM and point to PDGF receptor-β (PDGFRB) as a potential therapeutic target. A disease model using cardiomyocytes derived from induced pluripotent stem cells of patients with mutated LMNA-related dilated cardiomyopathy reveals that the abnormal activation of the PDGF pathway is associated with the arrhythmic phenotypes of patients.
Published: 2019
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32. Non-equivalence of Wnt and R-spondin ligands during Lgr5+intestinal stem-cell self-renewal

Author: Yan, Kelley S., Janda, Claudia Y., Chang, Junlei, Zheng, Grace X. Y., Larkin, Kathryn A., Luca, Vincent C., Chia, Luis A., Mah, Amanda T., Han, Arnold, Terry, Jessica M., Ootani, Akifumi, Roelf, Kelly, Lee, Mark, Yuan, Jenny, Li, Xiao, Bolen, Christopher R., Wilhelmy, Julie, Davies, Paige S., Ueno, Hiroo, von Furstenberg, Richard J., Belgrader, Phillip, Ziraldo, Solongo B., Ordonez, Heather, Henning, Susan J., Wong, Melissa H., Snyder, Michael P., Weissman, Irving L., Hsueh, Aaron J., Mikkelsen, Tarjei S., Garcia, K. Christopher, and Kuo, Calvin J.
Abstract: The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands. For example, individual mutations in Wnt ligands have not revealed homeostatic phenotypes in the intestinal epithelium—an archetypal canonical, Wnt pathway-dependent, rapidly self-renewing tissue, the regeneration of which is fueled by proliferative crypt Lgr5+intestinal stem cells (ISCs). R-spondin ligands (RSPO1–RSPO4) engage distinct LGR4–LGR6, RNF43 and ZNRF3 receptor classes, markedly potentiate canonical Wnt/β-catenin signalling, and induce intestinal organoid growth in vitro and Lgr5+ISCs in vivo. However, the interchangeability, functional cooperation and relative contributions of Wnt versus RSPO ligands to in vivo canonical Wnt signalling and ISC biology remain unknown. Here we identify the functional roles of Wnt and RSPO ligands in the intestinal crypt stem-cell niche. We show that the default fate of Lgr5+ISCs is to differentiate, unless both RSPO and Wnt ligands are present. However, gain-of-function studies using RSPO ligands and a new non-lipidated Wnt analogue reveal that these ligands have qualitatively distinct, non-interchangeable roles in ISCs. Wnt proteins are unable to induce Lgr5+ISC self-renewal, but instead confer a basal competency by maintaining RSPO receptor expression that enables RSPO ligands to actively drive and specify the extent of stem-cell expansion. This functionally non-equivalent yet cooperative interaction between Wnt and RSPO ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precise control of tissue regeneration.
Published: 2017
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33. Bent DNA at a yeast autonomously replicating sequence

Author: Snyder, Michael, Buchman, Andrew R., and Davis, Ronald W.
Abstract: DNA fragments that show retarded electrophoretic mobility through poly aery lamide gels have been found in both prokaryotes and eukaryotes1–7. In the case of kinetoplast DNA, evidence has been presented that the DNA is curved or ‘bent’8,9. Bent DNA has previously been found at the λand simian virus 40 (SV40) DNA replication origins6,7. Here we show the existence of bent DNA at a yeast autonomously replicating sequence (ARS1), a putative replication origin. The bent DNA has been localized to a 40–55 base pair (bp) segment and contains six (A)3–5stretches (that is, six poly(A) stretches, three to five nucleotides in length) phased approximately every 10.5 bp. This region contains a DNA binding site for a yeast protein factor. This site lies at the 3′ end of the TRP1gene, in a region devoid of nucleosomes, and is positioned 80 bp away from the ARS consensus sequence; removal of this region impairs ARS function in vivo. The bent DNA may be involved in transcription termination or the prevention of nucleosome assembly in this region.
Published: 1986
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34. Corrigendum: Regulatory analysis of the C. elegans genome with spatiotemporal resolution

Author: Araya, Carlos L., Kawli, Trupti, Kundaje, Anshul, Jiang, Lixia, Wu, Beijing, Vafeados, Dionne, Terrell, Robert, Weissdepp, Peter, Gevirtzman, Louis, Mace, Daniel, Niu, Wei, Boyle, Alan P., Xie, Dan, Ma, Lijia, Murray, John I., Reinke, Valerie, Waterston, Robert H., and Snyder, Michael
Published: 2015
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35. Recurrent repeat expansions in human cancer genomes.

Author: Erwin GS, Gürsoy G, Al-Abri R, Suriyaprakash A, Dolzhenko E, Zhu K, Hoerner CR, White SM, Ramirez L, Vadlakonda A, Vadlakonda A, von Kraut K, Park J, Brannon CM, Sumano DA, Kirtikar RA, Erwin AA, Metzner TJ, Yuen RKC, Fan AC, Leppert JT, Eberle MA, Gerstein M, and Snyder MP
Subjects: Humans, Base Sequence, Sequence Analysis, DNA, Gene Expression Regulation, Regulatory Elements, Transcriptional genetics, Introns genetics, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell pathology, Cell Proliferation drug effects, Reproducibility of Results, DNA Repeat Expansion genetics, Genome, Human genetics, Neoplasms classification, Neoplasms genetics, Neoplasms pathology
Abstract: Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases 1,2 . However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs, a phenomenon termed microsatellite instability; however, larger repeat expansions have not been systematically analysed in cancer 3-8 . Here we identified TR expansions in 2,622 cancer genomes spanning 29 cancer types. In seven cancer types, we found 160 recurrent repeat expansions (rREs), most of which (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with enrichment near candidate cis-regulatory elements, suggesting a potential role in gene regulation. One rRE, a GAAA-repeat expansion, located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, in preliminary experiments, treating cells that harbour this rRE with a GAAA-targeting molecule led to a dose-dependent decrease in cell proliferation. Overall, our results suggest that rREs may be an important but unexplored source of genetic variation in human cancer, and we provide a comprehensive catalogue for further study., (© 2022. The Author(s).)
Published: 2023
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35 results on '"Snyder, Michael P."'

1. Temporal dynamics of the multi-omic response to endurance exercise training

2. An exercise-inducible metabolite that suppresses feeding and obesity.

3. Author Correction: Perspectives on ENCODE

4. Author Correction: Expanded encyclopaedias of DNA elements in the human and mouse genomes

5. Perspectives on ENCODE

6. Expanded encyclopaedias of DNA elements in the human and mouse genomes

7. Expanded encyclopaedias of DNA elements in the human and mouse genomes.

8. Perspectives on ENCODE.

9. Physiological blood–brain transport is impaired with age by a shift in transcytosis

10. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

11. Activation of PDGF pathway links LMNA mutation to dilated cardiomyopathy.

12. Longitudinal multi-omics of host-microbe dynamics in prediabetes.

13. Comparative analysis of regulatory information and circuits across distant species

14. Landscape and variation of RNA secondary structure across the human transcriptome

15. Mapping copy number variation by population-scale genome sequencing.

16. The impact of rare variation on gene expression across tissues

17. Dynamic landscape and regulation of RNA editing in mammals

18. Landscape of X chromosome inactivation across human tissues

19. Recurrent repeat expansions in human cancer genomes

20. Genetic effects on gene expression across human tissues

21. Single-cell chromatin accessibility reveals principles of regulatory variation

22. Organization of the human intestine at single-cell resolution

23. Topologically associating domains are stable units of replication-timing regulation

24. A comparative encyclopedia of DNA elements in the mouse genome

25. Principles of regulatory information conservation between mouse and human

26. Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

27. Transcriptome variation in human tissues revealed by long-read sequencing

28. Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing

29. Landscape of cohesin-mediated chromatin loops in the human genome

30. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program.

31. Activation of PDGF pathway links LMNAmutation to dilated cardiomyopathy

32. Non-equivalence of Wnt and R-spondin ligands during Lgr5+intestinal stem-cell self-renewal

33. Bent DNA at a yeast autonomously replicating sequence

34. Corrigendum: Regulatory analysis of the C. elegans genome with spatiotemporal resolution

35. Recurrent repeat expansions in human cancer genomes.

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35 results on '"Snyder, Michael P."'

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