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51. The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models

Author

Rozowsky, Joel, primary, Drenkow, Jorg, additional, Yang, Yucheng T, additional, Gursoy, Gamze, additional, Galeev, Timur, additional, Borsari, Beatrice, additional, Epstein, Charles B, additional, Xiong, Kun, additional, Xu, Jinrui, additional, Gao, Jiahao, additional, Yu, Keyang, additional, Berthel, Ana, additional, Chen, Zhanlin, additional, Navarro, Fabio, additional, Liu, Jason, additional, Sun, Maxwell S, additional, Wright, James, additional, Chang, Justin, additional, Cameron, Christopher JF, additional, Shoresh, Noam, additional, Gaskell, Elizabeth, additional, Adrian, Jessika, additional, Aganezov, Sergey, additional, Aguet, François, additional, Balderrama-Gutierrez, Gabriela, additional, Banskota, Samridhi, additional, Corona, Guillermo Barreto, additional, Chee, Sora, additional, Chhetri, Surya B, additional, Cortez Martins, Gabriel Conte, additional, Danyko, Cassidy, additional, Davis, Carrie A, additional, Farid, Daniel, additional, Farrell, Nina P, additional, Gabdank, Idan, additional, Gofin, Yoel, additional, Gorkin, David U, additional, Gu, Mengting, additional, Hecht, Vivian, additional, Hitz, Benjamin C, additional, Issner, Robbyn, additional, Kirsche, Melanie, additional, Kong, Xiangmeng, additional, Lam, Bonita R, additional, Li, Shantao, additional, Li, Bian, additional, Li, Tianxiao, additional, Li, Xiqi, additional, Lin, Khine Zin, additional, Luo, Ruibang, additional, Mackiewicz, Mark, additional, Moore, Jill E, additional, Mudge, Jonathan, additional, Nelson, Nicholas, additional, Nusbaum, Chad, additional, Popov, Ioann, additional, Pratt, Henry E, additional, Qiu, Yunjiang, additional, Ramakrishnan, Srividya, additional, Raymond, Joe, additional, Salichos, Leonidas, additional, Scavelli, Alexandra, additional, Schreiber, Jacob M, additional, Sedlazeck, Fritz J, additional, See, Lei Hoon, additional, Sherman, Rachel M, additional, Shi, Xu, additional, Shi, Minyi, additional, Sloan, Cricket Alicia, additional, Strattan, J Seth, additional, Tan, Zhen, additional, Tanaka, Forrest Y, additional, Vlasova, Anna, additional, Wang, Jun, additional, Werner, Jonathan, additional, Williams, Brian, additional, Xu, Min, additional, Yan, Chengfei, additional, Yu, Lu, additional, Zaleski, Christopher, additional, Zhang, Jing, additional, Ardlie, Kristin, additional, Cherry, J Michael, additional, Mendenhall, Eric M, additional, Noble, William S, additional, Weng, Zhiping, additional, Levine, Morgan E, additional, Dobin, Alexander, additional, Wold, Barbara, additional, Mortazavi, Ali, additional, Ren, Bing, additional, Gillis, Jesse, additional, Myers, Richard M, additional, Snyder, Michael P, additional, Choudhary, Jyoti, additional, Milosavljevic, Aleksandar, additional, Schatz, Michael C, additional, Guigó, Roderic, additional, Bernstein, Bradley E, additional, Gingeras, Thomas R, additional, and Gerstein, Mark, additional

Published
2021
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53. Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer

Author

Johnstone, Sarah E., primary, Reyes, Alejandro, additional, Qi, Yifeng, additional, Adriaens, Carmen, additional, Hegazi, Esmat, additional, Pelka, Karin, additional, Chen, Jonathan H., additional, Zou, Luli S., additional, Drier, Yotam, additional, Hecht, Vivian, additional, Shoresh, Noam, additional, Selig, Martin K., additional, Lareau, Caleb A., additional, Iyer, Sowmya, additional, Nguyen, Son C., additional, Joyce, Eric F., additional, Hacohen, Nir, additional, Irizarry, Rafael A., additional, Zhang, Bin, additional, Aryee, Martin J., additional, and Bernstein, Bradley E., additional

Published
2020
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58. Publisher Correction : Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors (Nature Medicine, (2019), 25, 8, (1260-1265), 10.1038/s41591-019-0493-4)

Author

Cejas, Paloma, Drier, Yotam, Dreijerink, Koen M A, Brosens, Lodewijk A A, Deshpande, Vikram, Epstein, Charles B, Conemans, Elfi B, Morsink, Folkert H M, Graham, Mindy K, Valk, Gerlof D, Vriens, Menno R, Castillo, Carlos Fernandez-Del, Ferrone, Cristina R, Adar, Tomer, Bowden, Michaela, Whitton, Holly J, Da Silva, Annacarolina, Font-Tello, Alba, Long, Henry W, Gaskell, Elizabeth, Shoresh, Noam, Heaphy, Christopher M, Sicinska, Ewa, Kulke, Matthew H, Chung, Daniel C, Bernstein, Bradley E, Shivdasani, Ramesh A, Cejas, Paloma, Drier, Yotam, Dreijerink, Koen M A, Brosens, Lodewijk A A, Deshpande, Vikram, Epstein, Charles B, Conemans, Elfi B, Morsink, Folkert H M, Graham, Mindy K, Valk, Gerlof D, Vriens, Menno R, Castillo, Carlos Fernandez-Del, Ferrone, Cristina R, Adar, Tomer, Bowden, Michaela, Whitton, Holly J, Da Silva, Annacarolina, Font-Tello, Alba, Long, Henry W, Gaskell, Elizabeth, Shoresh, Noam, Heaphy, Christopher M, Sicinska, Ewa, Kulke, Matthew H, Chung, Daniel C, Bernstein, Bradley E, and Shivdasani, Ramesh A

Published
2019

59. Publisher Correction: Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors (Nature Medicine, (2019), 25, 8, (1260-1265), 10.1038/s41591-019-0493-4)

Author

Pathologie Groep Brosens, Cancer, Pathologie Pathologen staf, Pathologie, MS Endocriene Oncologie, Heelkunde Opleiding, MS CGO, Cejas, Paloma, Drier, Yotam, Dreijerink, Koen M A, Brosens, Lodewijk A A, Deshpande, Vikram, Epstein, Charles B, Conemans, Elfi B, Morsink, Folkert H M, Graham, Mindy K, Valk, Gerlof D, Vriens, Menno R, Castillo, Carlos Fernandez-Del, Ferrone, Cristina R, Adar, Tomer, Bowden, Michaela, Whitton, Holly J, Da Silva, Annacarolina, Font-Tello, Alba, Long, Henry W, Gaskell, Elizabeth, Shoresh, Noam, Heaphy, Christopher M, Sicinska, Ewa, Kulke, Matthew H, Chung, Daniel C, Bernstein, Bradley E, Shivdasani, Ramesh A, Pathologie Groep Brosens, Cancer, Pathologie Pathologen staf, Pathologie, MS Endocriene Oncologie, Heelkunde Opleiding, MS CGO, Cejas, Paloma, Drier, Yotam, Dreijerink, Koen M A, Brosens, Lodewijk A A, Deshpande, Vikram, Epstein, Charles B, Conemans, Elfi B, Morsink, Folkert H M, Graham, Mindy K, Valk, Gerlof D, Vriens, Menno R, Castillo, Carlos Fernandez-Del, Ferrone, Cristina R, Adar, Tomer, Bowden, Michaela, Whitton, Holly J, Da Silva, Annacarolina, Font-Tello, Alba, Long, Henry W, Gaskell, Elizabeth, Shoresh, Noam, Heaphy, Christopher M, Sicinska, Ewa, Kulke, Matthew H, Chung, Daniel C, Bernstein, Bradley E, and Shivdasani, Ramesh A

Published
2019

60. Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

Author

Divisie Beeld & Oncologie, Pathologie Groep Brosens, Cancer, Pathologie ICT innovatie & ontwikkeling, Pathologie Pathologen staf, Pathologie, MS Endocriene Oncologie, CTC, Heelkunde Opleiding, MS CGO, Cejas, Paloma, Drier, Yotam, Dreijerink, Koen M.A., Brosens, Lodewijk A.A., Deshpande, Vikram, Epstein, Charles B., Conemans, Elfi B., Morsink, Folkert H.M., Graham, Mindy K., Valk, Gerlof D., Vriens, Menno R., Castillo, Carlos Fernandez del, Ferrone, Cristina R., Adar, Tomer, Bowden, Michaela, Whitton, Holly J., Da Silva, Annacarolina, Font-Tello, Alba, Long, Henry W., Gaskell, Elizabeth, Shoresh, Noam, Heaphy, Christopher M., Sicinska, Ewa, Kulke, Matthew H., Chung, Daniel C., Bernstein, Bradley E., Shivdasani, Ramesh A., Divisie Beeld & Oncologie, Pathologie Groep Brosens, Cancer, Pathologie ICT innovatie & ontwikkeling, Pathologie Pathologen staf, Pathologie, MS Endocriene Oncologie, CTC, Heelkunde Opleiding, MS CGO, Cejas, Paloma, Drier, Yotam, Dreijerink, Koen M.A., Brosens, Lodewijk A.A., Deshpande, Vikram, Epstein, Charles B., Conemans, Elfi B., Morsink, Folkert H.M., Graham, Mindy K., Valk, Gerlof D., Vriens, Menno R., Castillo, Carlos Fernandez del, Ferrone, Cristina R., Adar, Tomer, Bowden, Michaela, Whitton, Holly J., Da Silva, Annacarolina, Font-Tello, Alba, Long, Henry W., Gaskell, Elizabeth, Shoresh, Noam, Heaphy, Christopher M., Sicinska, Ewa, Kulke, Matthew H., Chung, Daniel C., Bernstein, Bradley E., and Shivdasani, Ramesh A.

Published
2019

62. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues

Author

Yizhak, Keren, primary, Aguet, François, additional, Kim, Jaegil, additional, Hess, Julian M., additional, Kübler, Kirsten, additional, Grimsby, Jonna, additional, Frazer, Ruslana, additional, Zhang, Hailei, additional, Haradhvala, Nicholas J., additional, Rosebrock, Daniel, additional, Livitz, Dimitri, additional, Li, Xiao, additional, Arich-Landkof, Eila, additional, Shoresh, Noam, additional, Stewart, Chip, additional, Segrè, Ayellet V., additional, Branton, Philip A., additional, Polak, Paz, additional, Ardlie, Kristin G., additional, and Getz, Gad, additional

Published
2019
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63. A comprehensive analysis of RNA sequences reveals macroscopic somatic clonal expansion across normal tissues

Author

Yizhak, Keren, primary, Aguet, Francois, additional, Kim, Jaegil, additional, Hess, Julian, additional, Kubler, Kirsten, additional, Grimsby, Jonna, additional, Frazer, Ruslana, additional, Zhang, Hailei, additional, Haradhvala, Nicholas J., additional, Rosebrock, Daniel, additional, Livitz, Dimitri, additional, Li, Xiao, additional, Landkof, Eila-Arich, additional, Shoresh, Noam, additional, Stewart, Chip, additional, Segre, Ayelet, additional, Branton, Philip A., additional, Polak, Paz, additional, Ardlie, Kristin, additional, and Getz, Gad, additional

Published
2018
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64. Defining the core essential genome ofPseudomonas aeruginosa

Author

Poulsen, Bradley E., primary, Yang, Rui, additional, Clatworthy, Anne E., additional, White, Tiantian, additional, Osmulski, Sarah J., additional, Li, Li, additional, Penaranda, Cristina, additional, Lander, Eric S., additional, Shoresh, Noam, additional, and Hung, Deborah T., additional

Published
2018
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65. A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression

Author

Gupta, Rajat M., Hadaya, Joseph, Trehan, Aditi, Zekavat, Seyedeh M., Roselli, Carolina, Klarin, Derek, Emdin, Connor A., Hilvering, Catharina R.E., Bianchi, Valerio, Mueller, Christian, Khera, Amit V., Ryan, Russell J.H., Engreitz, Jesse M., Issner, Robbyn, Shoresh, Noam, Epstein, Charles B., de Laat, Wouter, Brown, Jonathan D., Schnabel, Renate B., Bernstein, Bradley E., Kathiresan, Sekar, Gupta, Rajat M., Hadaya, Joseph, Trehan, Aditi, Zekavat, Seyedeh M., Roselli, Carolina, Klarin, Derek, Emdin, Connor A., Hilvering, Catharina R.E., Bianchi, Valerio, Mueller, Christian, Khera, Amit V., Ryan, Russell J.H., Engreitz, Jesse M., Issner, Robbyn, Shoresh, Noam, Epstein, Charles B., de Laat, Wouter, Brown, Jonathan D., Schnabel, Renate B., Bernstein, Bradley E., and Kathiresan, Sekar

Published
2017

66. A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression

Author

Gupta, Rajat M, Hadaya, Joseph, Trehan, Aditi, Zekavat, Seyedeh M, Roselli, Carolina, Klarin, Derek, Emdin, Connor A, Hilvering, Catharina R E, Bianchi, Valerio, Mueller, Christian, Khera, Amit V, Ryan, Russell J H, Engreitz, Jesse M, Issner, Robbyn, Shoresh, Noam, Epstein, Charles B, de Laat, Wouter, Brown, Jonathan D, Schnabel, Renate B, Bernstein, Bradley E, Kathiresan, Sekar, Gupta, Rajat M, Hadaya, Joseph, Trehan, Aditi, Zekavat, Seyedeh M, Roselli, Carolina, Klarin, Derek, Emdin, Connor A, Hilvering, Catharina R E, Bianchi, Valerio, Mueller, Christian, Khera, Amit V, Ryan, Russell J H, Engreitz, Jesse M, Issner, Robbyn, Shoresh, Noam, Epstein, Charles B, de Laat, Wouter, Brown, Jonathan D, Schnabel, Renate B, Bernstein, Bradley E, and Kathiresan, Sekar

Abstract

Genome-wide association studies (GWASs) implicate the PHACTR1 locus (6p24) in risk for five vascular diseases, including coronary artery disease, migraine headache, cervical artery dissection, fibromuscular dysplasia, and hypertension. Through genetic fine mapping, we prioritized rs9349379, a common SNP in the third intron of the PHACTR1 gene, as the putative causal variant. Epigenomic data from human tissue revealed an enhancer signature at rs9349379 exclusively in aorta, suggesting a regulatory function for this SNP in the vasculature. CRISPR-edited stem cell-derived endothelial cells demonstrate rs9349379 regulates expression of endothelin 1 (EDN1), a gene located 600 kb upstream of PHACTR1. The known physiologic effects of EDN1 on the vasculature may explain the pattern of risk for the five associated diseases. Overall, these data illustrate the integration of genetic, phenotypic, and epigenetic analysis to identify the biologic mechanism by which a common, non-coding variant can distally regulate a gene and contribute to the pathogenesis of multiple vascular diseases.

Published
2017

67. A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression

Author

Divisie Biomedische Genetica, Hubrecht Institute with UMC, Cancer, Gupta, Rajat M., Hadaya, Joseph, Trehan, Aditi, Zekavat, Seyedeh M., Roselli, Carolina, Klarin, Derek, Emdin, Connor A., Hilvering, Catharina R.E., Bianchi, Valerio, Mueller, Christian, Khera, Amit V., Ryan, Russell J.H., Engreitz, Jesse M., Issner, Robbyn, Shoresh, Noam, Epstein, Charles B., de Laat, Wouter, Brown, Jonathan D., Schnabel, Renate B., Bernstein, Bradley E., Kathiresan, Sekar, Divisie Biomedische Genetica, Hubrecht Institute with UMC, Cancer, Gupta, Rajat M., Hadaya, Joseph, Trehan, Aditi, Zekavat, Seyedeh M., Roselli, Carolina, Klarin, Derek, Emdin, Connor A., Hilvering, Catharina R.E., Bianchi, Valerio, Mueller, Christian, Khera, Amit V., Ryan, Russell J.H., Engreitz, Jesse M., Issner, Robbyn, Shoresh, Noam, Epstein, Charles B., de Laat, Wouter, Brown, Jonathan D., Schnabel, Renate B., Bernstein, Bradley E., and Kathiresan, Sekar

Published
2017

68. Abstract LB-231: Identifying cancer-related processes in normal tissues via RNA-seq

Author

Yizhak, Keren, primary, Kim, Jaegil, additional, Aguet, Francois, additional, Hess, Julian, additional, Zhang, Hailei, additional, Arich-Landkof, Eila, additional, Shoresh, Noam, additional, Segre, Ayelet, additional, Stewart, Chip, additional, Rosebrock, Dainel, additional, Livitz, Dimitri, additional, Haradhvala, Nicholas, additional, Polak, Paz, additional, Sullivan, Tim, additional, Li, Xiao, additional, Ardlie, Kristin, additional, and Getz, Gad, additional

Published
2017
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69. A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression

Author

Gupta, Rajat M., primary, Hadaya, Joseph, additional, Trehan, Aditi, additional, Zekavat, Seyedeh M., additional, Roselli, Carolina, additional, Klarin, Derek, additional, Emdin, Connor A., additional, Hilvering, Catharina R.E., additional, Bianchi, Valerio, additional, Mueller, Christian, additional, Khera, Amit V., additional, Ryan, Russell J.H., additional, Engreitz, Jesse M., additional, Issner, Robbyn, additional, Shoresh, Noam, additional, Epstein, Charles B., additional, de Laat, Wouter, additional, Brown, Jonathan D., additional, Schnabel, Renate B., additional, Bernstein, Bradley E., additional, and Kathiresan, Sekar, additional

Published
2017
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71. Integrative analysis of 111 reference human epigenomes

Author

Roadmap Epigenomics Consortium, Kundaje, Anshul, Meuleman, Wouter, Ernst, Jason, Bilenky, Misha, Yen, Angela, Heravi-Moussavi, Alireza, Kheradpour, Pouya, Zhang, Zhizhuo, Wang, Jianrong, Ziller, Michael J., Amin, Viren, Whitaker, John W., Schultz, Matthew D., Ward, Lucas D., Sarkar, Abhishek, Quon, Gerald, Sandstrom, Richard S., Eaton, Matthew L., Wu, Yi-Chieh, Pfenning, Andreas R., Wang, Xinchen, Claussnitzer, Melina, Liu, Yaping, 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, Elliott, GiNell, Mercer, Tim R., Neph, Shane J., Onuchic, Vitor, Polak, Paz, Rajagopal, Nisha, Ray, Pradipta, Sallari, Richard C., Siebenthall, Kyle T., Sinnott-Armstrong, Nicholas A., Stevens, Michael, Thurman, Robert E., Wu, Jie, Zhang, Bo, Zhou, Xin, Beaudet, Arthur E., Boyer, Laurie A., De Jager, Philip L., Farnham, Peggy J., Fisher, Susan J., Haussler, David, Jones, Steven J.M., Li, Wei, Marra, Marco A., McManus, Michael T., Sunyaev, Shamil, Thomson, James A., Tlsty, Thea D., Tsai, Li-Huei, Wang, Wei, Waterland, Robert A., Zhang, Michael Q., 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, Roadmap Epigenomics Consortium, Kundaje, Anshul, Meuleman, Wouter, Ernst, Jason, Bilenky, Misha, Yen, Angela, Heravi-Moussavi, Alireza, Kheradpour, Pouya, Zhang, Zhizhuo, Wang, Jianrong, Ziller, Michael J., Amin, Viren, Whitaker, John W., Schultz, Matthew D., Ward, Lucas D., Sarkar, Abhishek, Quon, Gerald, Sandstrom, Richard S., Eaton, Matthew L., Wu, Yi-Chieh, Pfenning, Andreas R., Wang, Xinchen, Claussnitzer, Melina, Liu, Yaping, 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, Elliott, GiNell, Mercer, Tim R., Neph, Shane J., Onuchic, Vitor, Polak, Paz, Rajagopal, Nisha, Ray, Pradipta, Sallari, Richard C., Siebenthall, Kyle T., Sinnott-Armstrong, Nicholas A., Stevens, Michael, Thurman, Robert E., Wu, Jie, Zhang, Bo, Zhou, Xin, Beaudet, Arthur E., Boyer, Laurie A., De Jager, Philip L., Farnham, Peggy J., Fisher, Susan J., Haussler, David, Jones, Steven J.M., Li, Wei, Marra, Marco A., McManus, Michael T., Sunyaev, Shamil, Thomson, James A., Tlsty, Thea D., Tsai, Li-Huei, Wang, Wei, Waterland, Robert A., Zhang, Michael Q., 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, and Kellis, Manolis

Abstract

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease-and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease. © 2015 Macmillan Publishers Limited.

Published
2015

74. Comparative analysis of metazoan chromatin organization

Author

Ho, Joshua W. K., June, Youngsook L., Liu, Tao, Alver, Burak H., Lee, Soohyun, Ikegami, Kohta, Sohn, Kyung-Ah, Minoda, Aki, Tolstorukov, Michael Y., Appert, Alex, Parker, Stephen C. J., Gu, Tingting, Kundaje, Anshul, Riddle, Nicole C., Bishop, Eric, Egelhofer, Thea A., Hu, Sheng'en Shawn, Alekseyenko, Artyom A., Rechtsteiner, Andreas, Asker, Dalal, Belsky, Jason A., Bowmanm, Sarah K., Chens, Q. Brent, Chen, Ron A. -J., Day, Daniel S., Dong, Yan, Dose, Andrea C., Duan, Xikun, Epstein, Charles B., Ercan, Sevinc, Feingold, Elise A., Ferrari, Francesco, Garrigues, Jacob M., Gehlenborg, Nils, Good, Peter J., Haseley, Psalm, He, Daniel, Herrmann, Moritz, Hoffman, Michael M., Jeffers, Tess E., Kharchenko, Peter V., Kolasinska-Zwierz, Paulina, Kotwaliwale, Chitra V., Kumar, Nischay, Langley, Sasha A., Larschan, Erica N., Latorre, Isabel, Libbrecht, Maxwell W., Lin, Xueqiu, Park, Richard, Pazin, Michael J., Pham, Hoang N., Plachetka, Annette, Qin, Bo, Schwartz, Yuri B., Shoresh, Noam, Stempor, Przemyslaw, Vielle, Anne, Wang, Chengyang, Whittle, Christina M., Xue, Huiling, Kingstonm, Robert E., Kim, Ju Han, Bernstein, Bradley E., Dernburg, Abby F., Pirrotta, Vincenzo, Kuroda, Mitzi I., Noble, William S., Tullius, Thomas D., Kellis, Manolis, MacAlpine, David M., Strome, Susan, Elgin, Sarah C. R., Liu, Xiaole Shirley, Lieb, Jason D., Ahringer, Julie, Karpen, Gary H., Park, Peter J., Ho, Joshua W. K., June, Youngsook L., Liu, Tao, Alver, Burak H., Lee, Soohyun, Ikegami, Kohta, Sohn, Kyung-Ah, Minoda, Aki, Tolstorukov, Michael Y., Appert, Alex, Parker, Stephen C. J., Gu, Tingting, Kundaje, Anshul, Riddle, Nicole C., Bishop, Eric, Egelhofer, Thea A., Hu, Sheng'en Shawn, Alekseyenko, Artyom A., Rechtsteiner, Andreas, Asker, Dalal, Belsky, Jason A., Bowmanm, Sarah K., Chens, Q. Brent, Chen, Ron A. -J., Day, Daniel S., Dong, Yan, Dose, Andrea C., Duan, Xikun, Epstein, Charles B., Ercan, Sevinc, Feingold, Elise A., Ferrari, Francesco, Garrigues, Jacob M., Gehlenborg, Nils, Good, Peter J., Haseley, Psalm, He, Daniel, Herrmann, Moritz, Hoffman, Michael M., Jeffers, Tess E., Kharchenko, Peter V., Kolasinska-Zwierz, Paulina, Kotwaliwale, Chitra V., Kumar, Nischay, Langley, Sasha A., Larschan, Erica N., Latorre, Isabel, Libbrecht, Maxwell W., Lin, Xueqiu, Park, Richard, Pazin, Michael J., Pham, Hoang N., Plachetka, Annette, Qin, Bo, Schwartz, Yuri B., Shoresh, Noam, Stempor, Przemyslaw, Vielle, Anne, Wang, Chengyang, Whittle, Christina M., Xue, Huiling, Kingstonm, Robert E., Kim, Ju Han, Bernstein, Bradley E., Dernburg, Abby F., Pirrotta, Vincenzo, Kuroda, Mitzi I., Noble, William S., Tullius, Thomas D., Kellis, Manolis, MacAlpine, David M., Strome, Susan, Elgin, Sarah C. R., Liu, Xiaole Shirley, Lieb, Jason D., Ahringer, Julie, Karpen, Gary H., and Park, Peter J.

Abstract

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

Published
2014
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75. Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells

Author

Harvard University--MIT Division of Health Sciences and Technology, Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Kellis, Manolis, Ernst, Jason, Regev, Aviv, Gymrek, Melissa A., Coyne, Michael J., Ram, Oren, Goren, Alon, Amit, Ido, Shoresh, Noam, Yosef, Nir, Issner, Robbyn, Durham, Timothy, Zhang, Xiaolan, Donaghey, Julie, Epstein, Charles B., Bernstein, Bradley E., Harvard University--MIT Division of Health Sciences and Technology, Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Kellis, Manolis, Ernst, Jason, Regev, Aviv, Gymrek, Melissa A., Coyne, Michael J., Ram, Oren, Goren, Alon, Amit, Ido, Shoresh, Noam, Yosef, Nir, Issner, Robbyn, Durham, Timothy, Zhang, Xiaolan, Donaghey, Julie, Epstein, Charles B., and Bernstein, Bradley E.

Abstract

Hundreds of chromatin regulators (CRs) control chromatin structure and function by catalyzing and binding histone modifications, yet the rules governing these key processes remain obscure. Here, we present a systematic approach to infer CR function. We developed ChIP-string, a meso-scale assay that combines chromatin immunoprecipitation with a signature readout of 487 representative loci. We applied ChIP-string to screen 145 antibodies, thereby identifying effective reagents, which we used to map the genome-wide binding of 29 CRs in two cell types. We found that specific combinations of CRs colocalize in characteristic patterns at distinct chromatin environments, at genes of coherent functions, and at distal regulatory elements. When comparing between cell types, CRs redistribute to different loci but maintain their modular and combinatorial associations. Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function., National Human Genome Research Institute (U.S.) Center of Excellence in Genome Science (Grant), Howard Hughes Medical Institute, National Institutes of Health (U.S.). Pioneer Award, Burroughs Wellcome Fund

Published
2014

76. Genetic and epigenetic fine mapping of causal autoimmune disease variants

Author

Farh, Kyle Kai-How, primary, Marson, Alexander, additional, Zhu, Jiang, additional, Kleinewietfeld, Markus, additional, Housley, William J., additional, Beik, Samantha, additional, Shoresh, Noam, additional, Whitton, Holly, additional, Ryan, Russell J. H., additional, Shishkin, Alexander A., additional, Hatan, Meital, additional, Carrasco-Alfonso, Marlene J., additional, Mayer, Dita, additional, Luckey, C. John, additional, Patsopoulos, Nikolaos A., additional, De Jager, Philip L., additional, Kuchroo, Vijay K., additional, Epstein, Charles B., additional, Daly, Mark J., additional, Hafler, David A., additional, and Bernstein, Bradley E., additional

Published
2014
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77. Mapping and Analysis of Chromatin State Dynamics in Nine Human Cell Types

Author

Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. School of Science, Kellis, Manolis, Ernst, Jason, Kheradpour, Pouya, Ward, Lucas D., Epstein, Charles B., Coyne, Michael J., Ku, Manching, Mikkelsen, Tarjei Sigurd, Shoresh, Noam, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Durham, Timothy, Bernstein, Bradley E., Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. School of Science, Kellis, Manolis, Ernst, Jason, Kheradpour, Pouya, Ward, Lucas D., Epstein, Charles B., Coyne, Michael J., Ku, Manching, Mikkelsen, Tarjei Sigurd, Shoresh, Noam, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Durham, Timothy, and Bernstein, Bradley E.

Abstract

Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease., National Human Genome Research Institute (U.S.) (R01HG004037), National Human Genome Research Institute (U.S.) (RC1HG005334), National Science Foundation (U.S.). (Award 0644282), National Science Foundation (U.S.). (Award 0905968), Alfred P. Sloan Foundation

Published
2012

78. A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

Author

Broad Institute of MIT and Harvard, Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Department of Physics, Kellis, Manolis, Epstein, Charles B., Bernstein, Bradley E., Shoresh, Noam, Ernst, Jason, Mikkelsen, Tarjei Sigurd, Kheradpour, Pouya, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Ward, Lucas D., Altshuler, Robert Charles, Lin, Michael F., ENCODE Project Consortium, Broad Institute of MIT and Harvard, Lincoln Laboratory, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology. Department of Physics, Kellis, Manolis, Epstein, Charles B., Bernstein, Bradley E., Shoresh, Noam, Ernst, Jason, Mikkelsen, Tarjei Sigurd, Kheradpour, Pouya, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Ward, Lucas D., Altshuler, Robert Charles, Lin, Michael F., and ENCODE Project Consortium

Abstract

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

Published
2011

79. Genome-wide Chromatin State Transitions Associated with Developmental and Environmental Cues

Author

Zhu, Jiang, primary, Adli, Mazhar, additional, Zou, James Y., additional, Verstappen, Griet, additional, Coyne, Michael, additional, Zhang, Xiaolan, additional, Durham, Timothy, additional, Miri, Mohammad, additional, Deshpande, Vikram, additional, De Jager, Philip L., additional, Bennett, David A., additional, Houmard, Joseph A., additional, Muoio, Deborah M., additional, Onder, Tamer T., additional, Camahort, Ray, additional, Cowan, Chad A., additional, Meissner, Alexander, additional, Epstein, Charles B., additional, Shoresh, Noam, additional, and Bernstein, Bradley E., additional

Published
2013
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80. ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia

Author

Landt, Stephen G., primary, Marinov, Georgi K., additional, Kundaje, Anshul, additional, Kheradpour, Pouya, additional, Pauli, Florencia, additional, Batzoglou, Serafim, additional, Bernstein, Bradley E., additional, Bickel, Peter, additional, Brown, James B., additional, Cayting, Philip, additional, Chen, Yiwen, additional, DeSalvo, Gilberto, additional, Epstein, Charles, additional, Fisher-Aylor, Katherine I., additional, Euskirchen, Ghia, additional, Gerstein, Mark, additional, Gertz, Jason, additional, Hartemink, Alexander J., additional, Hoffman, Michael M., additional, Iyer, Vishwanath R., additional, Jung, Youngsook L., additional, Karmakar, Subhradip, additional, Kellis, Manolis, additional, Kharchenko, Peter V., additional, Li, Qunhua, additional, Liu, Tao, additional, Liu, X. Shirley, additional, Ma, Lijia, additional, Milosavljevic, Aleksandar, additional, Myers, Richard M., additional, Park, Peter J., additional, Pazin, Michael J., additional, Perry, Marc D., additional, Raha, Debasish, additional, Reddy, Timothy E., additional, Rozowsky, Joel, additional, Shoresh, Noam, additional, Sidow, Arend, additional, Slattery, Matthew, additional, Stamatoyannopoulos, John A., additional, Tolstorukov, Michael Y., additional, White, Kevin P., additional, Xi, Simon, additional, Farnham, Peggy J., additional, Lieb, Jason D., additional, Wold, Barbara J., additional, and Snyder, Michael, additional

Published
2012
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82. Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells

Author

Ram, Oren, primary, Goren, Alon, additional, Amit, Ido, additional, Shoresh, Noam, additional, Yosef, Nir, additional, Ernst, Jason, additional, Kellis, Manolis, additional, Gymrek, Melissa, additional, Issner, Robbyn, additional, Coyne, Michael, additional, Durham, Timothy, additional, Zhang, Xiaolan, additional, Donaghey, Julie, additional, Epstein, Charles B., additional, Regev, Aviv, additional, and Bernstein, Bradley E., additional

Published
2011
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96. Integrative analysis of 111 reference human epigenomes

Author

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, and Kellis, Manolis

Abstract

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 Epigenomics Consortium generated the largest collection to-date of human epigenomes for primary cells and tissues. Here, we describe the integrative analysis of 111 reference human epigenomes generated as part of the program, profiled for histone modification patterns, DNA accessibility, DNA methylation, and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically-relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation, and human disease.

Published
2015
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97. Chromatin profiling by directly sequencing small quantities of immunoprecipitated DNA.

Author

Goren, Alon, Ozsolak, Fatih, Shoresh, Noam, Ku, Manching, Adli, Mazhar, Hart, Chris, Gymrek, Melissa, Zuk, Or, Regev, Aviv, Milos, Patrice M., and Bernstein, Bradley E.

Subjects
TRANSCRIPTION factors, CHROMATIN, DNA, NUCLEOTIDE sequence, DNA-protein interactions
Abstract

Chromatin structure and transcription factor localization can be assayed genome-wide by sequencing genomic DNA fractionated by protein occupancy or other properties, but current technologies involve multiple steps that introduce bias and inefficiency. Here we apply a single-molecule approach to directly sequence chromatin immunoprecipitated DNA with minimal sample manipulation. This method is compatible with just 50 pg of DNA and should thus facilitate charting chromatin maps from limited cell populations. [ABSTRACT FROM AUTHOR]

Published
2010
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98. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types

Author

Finucane, Hilary K, Reshef, Yakir A, Anttila, Verneri, Slowikowski, Kamil, Gusev, Alexander, Byrnes, Andrea, Gazal, Steven, Loh, Po-Ru, Lareau, Caleb, Shoresh, Noam, Genovese, Giulio, Saunders, Arpiar, Macosko, Evan, Pollack, Samuela, Brainstorm Consortium, Perry, John RB, Buenrostro, Jason D, Bernstein, Bradley E, Raychaudhuri, Soumya, McCarroll, Steven, Neale, Benjamin M, and Price, Alkes L

Subjects
2. Zero hunger, Neurons, Multifactorial Inheritance, Bipolar Disorder, Models, Genetic, Gene Expression Profiling, Brain, Gene Expression, Chromatin, Linkage Disequilibrium, Body Mass Index, Epigenesis, Genetic, Immune System Diseases, Schizophrenia, Humans, Genetic Predisposition to Disease, Tissue Distribution, Genome-Wide Association Study
Abstract

We introduce an approach to identify disease-relevant tissues and cell types by analyzing gene expression data together with genome-wide association study (GWAS) summary statistics. Our approach uses stratified linkage disequilibrium (LD) score regression to test whether disease heritability is enriched in regions surrounding genes with the highest specific expression in a given tissue. We applied our approach to gene expression data from several sources together with GWAS summary statistics for 48 diseases and traits (average N = 169,331) and found significant tissue-specific enrichments (false discovery rate (FDR) < 5%) for 34 traits. In our analysis of multiple tissues, we detected a broad range of enrichments that recapitulated known biology. In our brain-specific analysis, significant enrichments included an enrichment of inhibitory over excitatory neurons for bipolar disorder, and excitatory over inhibitory neurons for schizophrenia and body mass index. Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signals.

99. Points of view: Data exploration.

Author

Shoresh, Noam and Wong, Bang

Subjects
*DATA visualization, *INFORMATION design, *PATTERNS (Mathematics), *PATTERN perception, *VISUAL analytics, *SCIENTIFIC communication
Abstract

The author discusses data visualization techniques to support data exploration. He particularly talks on the use of graphical representation of data to improve pattern discovery. He mentions the two uses of data visualization which are to communicate research results and to guide the data exploration process as the scientific story unfolds. Furthermore, he explains patterns, data exploration, and Anscombe's quartet.

Published
2012
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