Now showing items 1-20 of 29

    • The accessible chromatin landscape of the human genome 

      Thurman, Robert E.; Rynes, Eric; Humbert, Richard; Vierstra, Jeff; Maurano, Matthew T.; Haugen, Eric; Sheffield, Nathan C.; Stergachis, Andrew B.; Wang, Hao; Vernot, Benjamin; Garg, Kavita; Sandstrom, Richard; Bates, Daniel; Canfield, Theresa K.; Diegel, Morgan; Dunn, Douglas; Ebersol, Abigail K.; Frum, Tristan; Giste, Erika; Harding, Lisa; Johnson, Audra K.; Johnson, Ericka M.; Kutyavin, Tanya; Lajoie, Bryan; Lee, Bum-Kyu; Lee, Kristen; London, Darin; Lotakis, Dimitra; Neph, Shane; Neri, Fidencio; Nguyen, Eric D.; Reynolds, Alex P.; Roach, Vaughn; Safi, Alexias; Sanchez, Minerva E.; Sanyal, Amartya; Shafer, Anthony; Simon, Jeremy M.; Song, Lingyun; Vong, Shinny; Weaver, Molly; Zhang, Zhancheng; Zhang, Zhuzhu; Lenhard, Boris; Tewari, Muneesh; Dorschner, Michael O.; Hansen, R. Scott; Navas, Patrick A.; Stamatoyannopoulos, George; Iyer, Vishwanath R.; Lieb, Jason D.; Sunyaev, Shamil R.; Akey, Joshua M.; Sabo, Peter J.; Kaul, Rajinder; Furey, Terrence S.; Dekker, Job; Crawford, Gregory E.; Stamatoyannopoulos, John A. (2013)
      DNaseI 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. ...
    • Adaptive Mutations in the JC Virus Protein Capsid Are Associated with Progressive Multifocal Leukoencephalopathy (PML) 

      Sunyaev, Shamil R.; Lugovskoy, Alexey; Simon, Kenneth; Gorelik, Leonid (Public Library of Science, 2009)
      PML is a progressive and mostly fatal demyelinating disease caused by JC virus infection and destruction of infected oligodendrocytes in multiple brain foci of susceptible individuals. While JC virus is highly prevalent ...
    • Analysis of Sequence Conservation at Nucleotide Resolution 

      Asthana, Saurabh; Roytberg, Mikhail; Stamatoyannopoulos, John; Sunyaev, Shamil R. (Public Library of Science, 2007)
      One of the major goals of comparative genomics is to understand the evolutionary history of each nucleotide in the human genome sequence, and the degree to which it is under selective pressure. Ascertainment of selective ...
    • Assessing the Evolutionary Impact of Amino Acid Mutations in the Human Genome 

      Boyko, Adam R.; Indap, Amit R.; Degenhardt, Jeremiah D.; Hernandez, Ryan D.; Lohmueller, Kirk E.; Adams, Mark D.; Schmidt, Steffen; Sninsky, John J.; White, Thomas J.; Nielsen, Rasmus; Bustamante, Carlos D.; Williamson, Scott H.; Sunyaev, Shamil R.; Clark, Andrew G. (Public Library of Science, 2008)
      Quantifying the distribution of fitness effects among newly arising mutations in the human genome is key to resolving important debates in medical and evolutionary genetics. Here, we present a method for inferring this ...
    • Balancing Selection on a Regulatory Region Exhibiting Ancient Variation That Predates Human–Neandertal Divergence 

      Gokcumen, Omer; Zhu, Qihui; Mulder, Lubbertus C. F.; Iskow, Rebecca C.; Austermann, Christian; Scharer, Christopher D.; Raj, Towfique; Boss, Jeremy M.; Sunyaev, Shamil R.; Price, Alkes; Stranger, Barbara; Simon, Viviana; Lee, Charles (Public Library of Science, 2013)
      Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb ...
    • Biocomputing Enters its Adolescence 

      Sunyaev, Shamil R. (BioMed Central, 2005)
    • Cell-of-origin chromatin organization shapes the mutational landscape of cancer 

      Polak, Paz; Karlić, Rosa; Koren, Amnon; Thurman, Robert; Sandstrom, Richard; Lawrence, Michael; Reynolds, Alex; Rynes, Eric; Vlahoviček, Kristian; Stamatoyannopoulos, John A.; Sunyaev, Shamil R. (2015)
      Cancer is a disease potentiated by mutations in somatic cells. Cancer mutations are not distributed uniformly along the genome. Instead, different genomic regions vary by up to 5-fold in the local density of somatic ...
    • Computational and Statistical Approaches to Analyzing Variants Identified by Exome Sequencing 

      Stitziel, Nathan O.; Kiezun, Adam; Sunyaev, Shamil R. (BioMed Central, 2011)
      New sequencing technology has enabled the identification of thousands of single nucleotide polymorphisms in the exome, and many computational and statistical approaches to identify disease-association signals have emerged.
    • Deleterious Alleles in the Human Genome Are on Average Younger Than Neutral Alleles of the Same Frequency 

      Kiezun, Adam; Pulit, Sara L.; Francioli, Laurent C.; van Dijk, Freerk; Swertz, Morris; Boomsma, Dorret I.; van Duijn, Cornelia M.; Slagboom, P. Eline; van Ommen, G. J. B.; Wijmenga, Cisca; de Bakker, Paul I Wen; Sunyaev, Shamil R. (Public Library of Science, 2013)
      Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect ...
    • Dominance of Deleterious Alleles Controls the Response to a Population Bottleneck 

      Balick, Daniel J.; Do, Ron; Cassa, Christopher A.; Reich, David; Sunyaev, Shamil R. (Public Library of Science, 2015)
      Population bottlenecks followed by re-expansions have been common throughout history of many populations. The response of alleles under selection to such demographic perturbations has been a subject of great interest in ...
    • Excess of Deleterious Mutations around HLA Genes Reveals Evolutionary Cost of Balancing Selection 

      Lenz, Tobias L.; Spirin, Victor; Jordan, Daniel M.; Sunyaev, Shamil R. (Oxford University Press, 2016)
      Deleterious mutations are expected to evolve under negative selection and are usually purged from the population. However, deleterious alleles segregate in the human population and some disease-associated variants are ...
    • Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis 

      Coste, B.; Houge, G.; Murray, M. F.; Stitziel, N.; Bandell, M.; Giovanni, M. A.; Philippakis, A.; Hoischen, A.; Riemer, G.; Steen, U.; Steen, V. M.; Mathur, J.; Cox, J.; Lebo, M.; Rehm, H.; Weiss, Scott Tillman; Wood, J. N.; Maas, R. L.; Sunyaev, Shamil R.; Patapoutian, A. (Proceedings of the National Academy of Sciences, 2013)
      Mechanotransduction, the pathway by which mechanical forces are translated to biological signals, plays important but poorly characterized roles in physiology. PIEZOs are recently identified, widely expressed, mechanically ...
    • Genes with monoallelic expression contribute disproportionately to genetic diversity in humans 

      Savova, Virginia; Chun, Sung; Sohail, Mashaal; McCole, Ruth B.; Witwicki, Robert; Gai, Lisa; Lenz, Tobias L.; Wu, C.-ting; Sunyaev, Shamil R.; Gimelbrant, Alexander A. (2016)
      An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes reveals surprisingly high genetic variation across human populations. This increased ...
    • Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii 

      Seim, Inge; Fang, Xiaodong; Xiong, Zhiqiang; Lobanov, Alexey V.; Huang, Zhiyong; Ma, Siming; Feng, Yue; Turanov, Anton A.; Zhu, Yabing; Lenz, Tobias L.; Gerashchenko, Maxim V.; Fan, Dingding; Hee Yim, Sun; Yao, Xiaoming; Jordan, Daniel; Xiong, Yingqi; Ma, Yong; Lyapunov, Andrey N.; Chen, Guanxing; Kulakova, Oksana I.; Sun, Yudong; Lee, Sang-Goo; Bronson, Roderick T.; Moskalev, Alexey A.; Sunyaev, Shamil R.; Zhang, Guojie; Krogh, Anders; Wang, Jun; Gladyshev, Vadim N. (Nature Pub. Group, 2013)
      Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt’s bat (Myotis brandtii) is the longest-lived bat species ...
    • Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels 

      van Leeuwen, Elisabeth M.; Karssen, Lennart C.; Deelen, Joris; Isaacs, Aaron; Medina-Gomez, Carolina; Mbarek, Hamdi; Kanterakis, Alexandros; Trompet, Stella; Postmus, Iris; Verweij, Niek; van Enckevort, David J.; Huffman, Jennifer E.; White, Charles C.; Feitosa, Mary F.; Bartz, Traci M.; Manichaikul, Ani; Joshi, Peter K.; Peloso, Gina M.; Deelen, Patrick; van Dijk, Freerk; Willemsen, Gonneke; de Geus, Eco J.; Milaneschi, Yuri; Penninx, Brenda W.J.H.; Francioli, Laurent C.; Menelaou, Androniki; Pulit, Sara L.; Rivadeneira, Fernando; Hofman, Albert; Oostra, Ben A.; Franco, Oscar H.; Leach, Irene Mateo; Beekman, Marian; de Craen, Anton J.M.; Uh, Hae-Won; Trochet, Holly; Hocking, Lynne J.; Porteous, David J.; Sattar, Naveed; Packard, Chris J.; Buckley, Brendan M.; Brody, Jennifer A.; Bis, Joshua C.; Rotter, Jerome I.; Mychaleckyj, Josyf C.; Campbell, Harry; Duan, Qing; Lange, Leslie A.; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Vitart, Veronique; Rudan, Igor; Wright, Alan F.; Rich, Stephen S.; Psaty, Bruce M.; Borecki, Ingrid B.; Kearney, Patricia M.; Stott, David J.; Adrienne Cupples, L.; Neerincx, Pieter B.T.; Elbers, Clara C.; Francesco Palamara, Pier; Pe'er, Itsik; Abdellaoui, Abdel; Kloosterman, Wigard P.; van Oven, Mannis; Vermaat, Martijn; Li, Mingkun; Laros, Jeroen F.J.; Stoneking, Mark; de Knijff, Peter; Kayser, Manfred; Veldink, Jan H.; van den Berg, Leonard H.; Byelas, Heorhiy; den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Joeri van der Velde, K.; van Setten, Jessica; Kattenberg, Mathijs; van Schaik, Barbera D.C.; Bot, Jan; Nijman, Isaäc J.; Mei, Hailiang; Koval, Vyacheslav; Ye, Kai; Lameijer, Eric-Wubbo; Moed, Matthijs H.; Hehir-Kwa, Jayne Y.; Handsaker, Robert E.; Sunyaev, Shamil R.; Sohail, Mashaal; Hormozdiari, Fereydoun; Marschall, Tobias; Schönhuth, Alexander; Guryev, Victor; Suchiman, H. Eka D.; Wolffenbuttel, Bruce H.; Platteel, Mathieu; Pitts, Steven J.; Potluri, Shobha; Cox, David R.; Li, Qibin; Li, Yingrui; Du, Yuanping; Chen, Ruoyan; Cao, Hongzhi; Li, Ning; Cao, Sujie; Wang, Jun; Bovenberg, Jasper A.; Jukema, J. Wouter; van der Harst, Pim; Sijbrands, Eric J.; Hottenga, Jouke-Jan; Uitterlinden, Andre G.; Swertz, Morris A.; van Ommen, Gert-Jan B.; de Bakker, Paul I.W.; Eline Slagboom, P.; Boomsma, Dorret I.; Wijmenga, Cisca; van Duijn, Cornelia M. (Nature Pub. Group, 2015)
      Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch ...
    • Genome-wide association study reveals class I MHC–restricted T cell–associated molecule gene (CRTAM) variants interact with vitamin D levels to affect asthma exacerbations 

      Du, Rose; Litonjua, Augusto Ampil; Tantisira, Kelan; Lasky-Su, Jessica A. Lasky; Sunyaev, Shamil R.; Klanderman, Barbara; Celedón, Juan C.; Avila, Lydiana; Soto-Quiros, Manuel E.; Weiss, Scott Tillman (Elsevier BV, 2012)
      Background— It has recently been shown that vitamin D deficiency can increase asthma development and severity and that variations in vitamin D receptor genes are associated with asthma susceptibility. Objective— We sought ...
    • Genome-wide patterns and properties of de novo mutations in humans 

      Francioli, Laurent C.; Polak, Paz P.; Koren, Amnon; Menelaou, Androniki; Chun, Sung; Renkens, Ivo; van Duijn, Cornelia M.; Swertz, Morris; Wijmenga, Cisca; van Ommen, Gertjan; Slagboom, P. Eline; Boomsma, Dorret I.; Ye, Kai; Guryev, Victor; Arndt, Peter F.; Kloosterman, Wigard P.; de Bakker, Paul I. W.; Sunyaev, Shamil R. (2015)
      Mutations create variation in the population, fuel evolution, and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect 1–10. Here, we analyze 11,020 de novo mutations from ...
    • Genomic variation landscape of the human gut microbiome 

      Schloissnig, Siegfried; Arumugam, Manimozhiyan; Sunagawa, Shinichi; Mitreva, Makedonka; Tap, Julien; Zhu, Ana; Waller, Alison; Mende, Daniel R.; Kultima, Jens Roat; Martin, John; Kota, Karthik; Sunyaev, Shamil R.; Weinstock, George M.; Bork, Peer (2012)
      While large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the latter is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic ...
    • Hypermutable Non-Synonymous Sites are Under Stronger Negative Selection 

      Schmidt, Steffen; Gerasimova, Anna; Kondrashov, Fyodor A.; Adzuhbei, Ivan A.; Kondrashov, Alexey S.; Sunyaev, Shamil R. (Public Library of Science, 2008)
      Mutation rate varies greatly between nucleotide sites of the human genome and depends both on the global genomic location and the local sequence context of a site. In particular, CpG context elevates the mutation rate by ...
    • Integrative analysis of 111 reference human epigenomes 

      Kundaje, Anshul; Meuleman, Wouter; Ernst, Jason; Bilenky, Misha; Yen, Angela; Kheradpour, Pouya; Zhang, Zhizhuo; Heravi-Moussavi, Alireza; Liu, Yaping; Amin, Viren; Ziller, Michael J; Whitaker, John W; Schultz, Matthew D; Sandstrom, Richard S; Eaton, Matthew L; Wu, Yi-Chieh; Wang, Jianrong; Ward, Lucas D; Sarkar, Abhishek; Quon, Gerald; Pfenning, Andreas; Wang, Xinchen; Claussnitzer, Melina; Coarfa, Cristian; Harris, R Alan; Shoresh, Noam; Epstein, Charles B; Gjoneska, Elizabeta; Leung, Danny; Xie, Wei; Hawkins, R David; Lister, Ryan; Hong, Chibo; Gascard, Philippe; Mungall, Andrew J; Moore, Richard; Chuah, Eric; Tam, Angela; Canfield, Theresa K; Hansen, R Scott; Kaul, Rajinder; Sabo, Peter J; Bansal, Mukul S; Carles, Annaick; Dixon, Jesse R; Farh, Kai-How; Feizi, Soheil; Karlic, Rosa; Kim, Ah-Ram; Kulkarni, Ashwinikumar; Li, Daofeng; Lowdon, Rebecca; Mercer, Tim R; Neph, Shane J; Onuchic, Vitor; Polak, Paz; Rajagopal, Nisha; Ray, Pradipta; Sallari, Richard C; Siebenthall, Kyle T; Sinnott-Armstrong, Nicholas; Stevens, Michael; Thurman, Robert E; Wu, Jie; Zhang, Bo; Zhou, Xin; Beaudet, Arthur E; Boyer, Laurie A; De Jager, Philip; Farnham, Peggy J; Fisher, Susan J; Haussler, David; Jones, Steven; Li, Wei; Marra, Marco; McManus, Michael T; Sunyaev, Shamil; Thomson, James A; Tlsty, Thea D; Tsai, Li-Huei; Wang, Wei; Waterland, Robert A; Zhang, Michael; Chadwick, Lisa H; Bernstein, Bradley E; Costello, Joseph F; Ecker, Joseph R; Hirst, Martin; Meissner, Alexander; Milosavljevic, Aleksandar; Ren, Bing; Stamatoyannopoulos, John A; Wang, Ting; Kellis, Manolis (2015)
      The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but a similar reference has lacked for epigenomic studies. To address this need, the NIH Roadmap ...