19 results on '"Dennis C. Friedrich"'
Number of results to display per page
Search Results
2. Supplementary Table 6 from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
- Author
-
Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle
- Abstract
XLSX file 31K, Coverage and Metrics
- Published
- 2023
- Full Text
- View/download PDF
3. Supplementary Table 4 from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
- Author
-
Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle
- Abstract
XLSX file 12K, Candidate Resistance Genes from RNAi and ORF Functional Screens
- Published
- 2023
- Full Text
- View/download PDF
4. Supplementary Table 3 from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
- Author
-
Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle
- Abstract
XLSX file 3709K, Alterations with Significantly Enriched CCF from Pretreatment to Resistant
- Published
- 2023
- Full Text
- View/download PDF
5. Supplementary Table 1 from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
- Author
-
Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle
- Abstract
XLS file 6188K, Annotated SNVs and Indels in All Samples
- Published
- 2023
- Full Text
- View/download PDF
6. Supplementary Table 5 from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
- Author
-
Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle
- Abstract
XLSX file 90K, Alterations in Each Patient in Genes that Scored in Functional Screens
- Published
- 2023
- Full Text
- View/download PDF
7. Supplementary Figures from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
- Author
-
Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle
- Abstract
PDF file 550K, Contains supplementary figures 1-3
- Published
- 2023
- Full Text
- View/download PDF
8. Data Supplement from MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition
- Author
-
Levi A. Garraway, Jennifer A. Wargo, Keith T. Flaherty, Scott L. Carter, Stacey B. Gabriel, Gad Getz, Sheila Fisher, Donald P. Lawrence, Eran Hodis, Gregory Kryukov, Kristian Cibulskis, Aaron McKenna, Cory M. Johannessen, Danielle Perrin, Kristin Anderka, Dennis C. Friedrich, Deborah N. Farlow, Ryan J. Sullivan, Eva M. Goetz, Mara Rosenberg, Amaro Taylor-Weiner, Zachary A. Cooper, Dennie T. Frederick, Daniel J. Treacy, Eliezer M. Van Allen, and Nikhil Wagle
- Abstract
PDF file 171K, Contains Supplementary Data and Methods
- Published
- 2023
- Full Text
- View/download PDF
9. Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine
- Author
-
Franklin W. Huang, Judit Jané-Valbuena, Pasi A. Jänne, Stacy W. Gray, Sara Marlow, Andrey Sivachenko, Danielle Perrin, Aaron McKenna, David A. Barbie, Michael S. Lawrence, Jennifer L. Fostel, Laura E. MacConaill, Petar Stojanov, Scott L. Carter, Steven Joffe, Stacey Gabriel, Sheila Fisher, Lee Lichtenstein, Kristian Cibulskis, Douglas Voet, Nikhil Wagle, Neal I. Lindeman, Jeff Gentry, Judy Garber, Gregory V. Kryukov, Philip W. Kantoff, Dennis C. Friedrich, Leena Gandhi, Gad Getz, Deborah N. Farlow, Adam Kiezun, Mara Rosenberg, Levi A. Garraway, Eliezer M. Van Allen, Barrett J. Rollins, and Eric S. Lander
- Subjects
medicine.medical_specialty ,Clinical pathology ,business.industry ,MEDLINE ,Cancer ,General Medicine ,Precision medicine ,Bioinformatics ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,3. Good health ,Clinical trial ,Cancer Medicine ,medicine ,business ,Exome ,Exome sequencing - Abstract
Translating whole-exome sequencing (WES) for prospective clinical use may have an impact on the care of patients with cancer; however, multiple innovations are necessary for clinical implementation. These include rapid and robust WES of DNA derived from formalin-fixed, paraffin-embedded tumor tissue, analytical output similar to data from frozen samples and clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival formalin-fixed, paraffin-embedded tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a 'long tail' of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15 out of 16 patients. In one patient, previously undetected findings guided clinical trial enrollment, leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine.
- Published
- 2014
- Full Text
- View/download PDF
10. A framework for human microbiome research
- Author
-
Rosamond Rhodes, Asif T. Chinwalla, Tessa Madden, Ashlee M. Earl, Maria C. Rivera, Candace N. Farmer, Jonathan M. Goldberg, Karthik Kota, Victor Felix, Nicholas B. King, Shibu Yooseph, Erica Sodergren, Monika Bihan, Martin J. Blaser, Dirk Gevers, Dan Knights, Pamela Sankar, Anup Mahurkar, Heather Huot Creasy, Veena Bhonagiri, Thomas M. Schmidt, Curtis Huttenhower, Mina Rho, Todd J. Treangen, Thomas J. Sharpton, I. Min A. Chen, Bo Liu, Sarah K. Highlander, Catherine C. Davis, Susan M. Huse, Richard A. Gibbs, Noam J. Davidovics, Patricio S. La Rosa, Carsten Russ, Wesley C. Warren, Richard K. Wilson, Patrick Minx, Jean E. McEwen, Alyxandria M. Schubert, Scott Anderson, Bonnie P. Youmans, Jamison McCorrison, Kathie A. Mihindukulasuriya, Vandita Joshi, Peter J. Mannon, Brandi L. Cantarel, Joseph F. Petrosino, Jack D. Sobel, Chandri Yandava, Sharvari Gujja, Janet K. Jansson, David J. Dooling, Daniel McDonald, Rob Knight, Granger G. Sutton, Gary C. Armitage, Larry J. Forney, Robert S. Fulton, Yuan Qing Wu, Jonathan Crabtree, Susan Kinder-Haake, Lu Wang, Liang Ye, Victor M. Markowitz, Narmada Shenoy, Elizabeth A. Lobos, Ruth M. Farrell, Tatiana A. Vishnivetskaya, Patrick S. G. Chain, Jacques Ravel, Katherine H. Huang, Sergey Koren, Yan Ding, Christina Giblin, Jason R. Miller, Michelle G. Giglio, Gina A. Simone, Chad Nusbaum, Lynn M. Schriml, Matthew C. Ross, Daniel D. Sommer, Sandra L. Lee, Theresa A. Hepburn, Michael Holder, Shaila Chhibba, Patrick D. Schloss, Omry Koren, Lan Zhang, Catrina Fronick, Richard R. Sharp, Diana Tabbaa, Yuzhen Ye, Dennis C. Friedrich, Christie Kovar, Owen White, A. Scott Durkin, Michael Feldgarden, Gary L. Andersen, Makedonka Mitreva, Todd Wylie, Nihar U. Sheth, Sheila Fisher, John Martin, Jose C. Clemente, Xiang Qin, James Versalovic, Dana A. Busam, Bruce W. Birren, Jeremy Zucker, Yu-Hui Rogers, Shannon Dugan, Kristine M. Wylie, Katherine P. Lemon, Floyd E. Dewhirst, Nicola Segata, Konstantinos Liolios, Anthony A. Fodor, Elizabeth L. Appelbaum, Ramana Madupu, W. Michael Dunne, Katherine S. Pollard, Leslie Foster, Olukemi O. Abolude, Yue Liu, Nikos C. Kyrpides, Christopher Wellington, Yanjiao Zhou, Lita M. Proctor, Tsegahiwot Belachew, Mircea Podar, Julia A. Segre, Holli A. Hamilton, Aye Wollam, Paul Spicer, Lei Chen, Sarah Young, Beltran Rodriguez-Mueller, Todd Z. DeSantis, Sean M. Sykes, Toby Bloom, Kelvin Li, Shane Canon, Catherine Jordan, Manolito Torralba, Brandi Herter, R. Dwayne Lunsford, Krishna Palaniappan, Jeroen Raes, Hongyu Gao, Barbara A. Methé, Kjersti Aagaard, Amy L. McGuire, Jonathan Friedman, Matthew D. Pearson, Jason Walker, Mary A. Cutting, Jonathan H. Badger, Diane E. Hoffmann, Tulin Ayvaz, Michael Fitzgerald, Brian J. Haas, Ravi Sanka, Doyle V. Ward, Kris A. Wetterstrand, Mark A. Watson, Christopher Smillie, Lucinda Fulton, Zhengyuan Wang, Lisa Begg, James R. White, Konstantinos Mavrommatis, Lucia Alvarado, Pamela McInnes, Emily L. Harris, Harindra Arachchi, Craig Pohl, Catherine A. Lozupone, Ruth E. Ley, Clinton Howarth, Yiming Zhu, Huaiyang Jiang, Gregory A. Buck, Carl C. Baker, Kimberley D. Delehaunty, Cristyn Kells, Katarzyna Wilczek-Boney, Kim C. Worley, Cesar Arze, J. Fah Sathirapongsasuti, Carolyn Deal, Sandra W. Clifton, Ken Chu, Rachel L. Erlich, Elaine R. Mardis, Cecil M. Lewis, Niall Lennon, Margaret Priest, Scott T. Kelley, Kymberlie Hallsworth-Pepin, Jane Peterson, Allison D. Griggs, Michelle O'Laughlin, Heidi H. Kong, Joshua Orvis, Maria Y. Giovanni, Sahar Abubucker, Dawn Ciulla, Sean Conlan, Chien Chi Lo, Antonio Gonzalez, Georgia Giannoukos, Jennifer R. Wortman, Paul Brooks, Jacques Izard, Chad Tomlinson, Donna M. Muzny, Shital M. Patel, Eric J. Alm, George M. Weinstock, Irene Newsham, Jeffrey G. Reid, Karoline Faust, Qiandong Zeng, Elena Deych, Nathalia Garcia, Mathangi Thiagarajan, James A. Katancik, Vivien Bonazzi, Robert C. Edgar, Christian J. Buhay, Indresh Singh, Johannes B. Goll, Ioanna Pagani, Vincent Magrini, Wendy A. Keitel, Emma Allen-Vercoe, Teena Mehta, Jeffery A. Schloss, William D. Shannon, Mihai Pop, Matthew B. Scholz, Valentina Di Francesco, Rebecca Truty, Karen E. Nelson, Kevin Riehle, Lora Lewis, Joseph L. Campbell, Laurie Zoloth, Massachusetts Institute of Technology. Computational and Systems Biology Program, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Civil and Environmental Engineering, Friedman, Jonathan, Smillie, Chris Scott, and Alm, Eric J.
- Subjects
Adult ,Male ,Adolescent ,Statistics as Topic ,Population ,Computational biology ,Biology ,Genome ,Article ,Young Adult ,03 medical and health sciences ,Human health ,0302 clinical medicine ,RNA, Ribosomal, 16S ,Humans ,Microbiome ,education ,030304 developmental biology ,Genetics ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,Bacteria ,Human microbiome ,Reference Standards ,Metagenomics ,030220 oncology & carcinogenesis ,Earth Microbiome Project ,Metagenome ,Female ,Human Microbiome Project - Abstract
A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies.
- Published
- 2012
11. Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
- Author
-
Frances Letendre, Vasilia Magnisalis, Helen Vassiliev, Rebecca Reyes, Maura Costello, St Christophe Acer, Pen MacDonald, Geneva Young, Katherine Thompson, Iain MacCallum, Tarjei S. Mikkelsen, Andy Vo, Eva Markiewicz, Yeshi Lokyitsang, Sharon Stavropoulos, Rachel Mittelman, Xiaohui Xie, Diallo Ferguson, James Cuff, Terence P. Speed, Catherine Stone, Tanya Mihova, Janine E. Deakin, Aaron M. Berlin, David A. Ray, David D. Pollock, Ben Kanga, Kunsang Gyaltsen, Scott Anderson, Gary Gearin, Nabil Hafez, Lisa Chuda, Marco A. Marra, David B. Jaffe, Leonid Boguslavskiy, Asha Kamat, Jonathan Butler, Alicia Franke, Lynne Aftuck, Sheridon Channer, Rosie Levine, Kerstin Lindblad-Toh, Birhane Hagos, Imane Bourzgui, Monika D. Huard, Tamrat Negash, Jamal Abdulkadir, Tsering Wangchuk, Georgius De Haan, Sheila Fisher, Justin Abreu, Abderrahim Farina, Kebede Maru, M. Erii Husby, Peter Kisner, Kunsang Dorjee, Jacob L. Glass, Tashi Lokyitsang, Nyima Norbu, Jennifer Baldwin, Christina R. Gearin, Otero L. Oyono, Atanas Mihalev, Yama Thoulutsang, Katie D'Aco, Choe Norbu, Christopher Strader, Edda Koina, Allen Alexander, Barry O'Neill, William Brockman, Wanjun Gu, Richard Elong, Keenan Ross, Shailendra Yadav, Alan Dupes, Seva Kashin, James Meldrim, Dmitry Khazanovich, Passang Dorje, Adal Abebe, April Cook, Matthew Breen, Randy L. Jirtle, Shangtao Liu, Jean L. Chang, Patrick Cahill, Claire M. Wade, Chee Whye Chin, Dennis C. Friedrich, Tina Goode, Cecil Rise, Robert D. Nicholls, Peter Rogov, Adam Brown, Oana Mihai, Sujaa Raghuraman, Adam Wilson, Marcia Lara, Chelsea D. Foley, Susan Faro, Sampath Settipalli, Thu Nguyen, Matthew Wakefield, Xiaohong Liu, Anna Montmayeur, Jerzy Jurka, Ngawang Sherpa, Riza M. Daza, Evan Mauceli, Senait Tesfaye, Sharleen Grewal, Susan McDonough, Leo Goodstadt, Manuel Garber, John M. Greally, Valentine Mlenga, Manfred Grabherr, Charles Matthews, Andrew Zimmer, Teena Mehta, Harindra Arachi, Mark A. Batzer, Rakela Lubonja, Margaret Priest, Diana Shih, Joseph Graham, Panayiotis V. Benos, Lance S. Davidow, Alex Lipovsky, Stephen M. J. Searle, Andreas Heger, Timothy A. Hore, Patrick Cooke, Leonidas Mulrain, Tsering Wangdi, Jennifer A. Marshall Graves, Sante Gnerre, Michelle L. Baker, Jacqueline E. Schein, Michael Weiand, Jessica Spaulding, Charlotte Henson, Jane Wilkinson, Terry Shea, Shannon E. Duke, William McCusker, Kerri Topham, Jerome Naylor, Lu Shi, Fritz Pierre, Claude Bonnet, Shaun Mahony, Michele Clamp, Katherine Belov, John L. VandeBerg, Nicole Stange-Thomann, Annie Lui, Radhika Das, Pema Phunkhang, Andrew J. Gentles, Elizabeth P. Ryan, Erica Anderson, Jill Falk, Bronwen Aken, Robert Nicol, Ted Sharpe, Sahal Osman, Missole Doricent, Michael Kleber, Jeannie T. Lee, Paul D. Waters, Melissa Fazzari, Jinlei Liu, Loryn Gadbois, Lisa Zembek, Daniel Bessette, Pasang Bachantsang, Adam Navidi, Caleb Webber, Tashi Bayul, Brikti Abera, Mayumi Oda, Gavin A. Huttley, Jennifer L. Hall, Chris P. Ponting, Michael Kamal, Kimberly Dooley, Mieke Citroen, Tsamla Tsamla, Ira Topping, Eric S. Lander, Edward Grandbois, Christopher Patti, Louis Meneus, Tracey Honan, Zuly E. Parra, Nga Nguyen, Todd Sparrow, Dawa Thoulutsang, Leanne Hughes, Yama Cheshatsang, Qing Yu, Niall J. Lennon, Nathaniel Novod, Christina Demaso, Anthony T. Papenfuss, Paul B. Samollow, Toby Bloom, Andrew Hollinger, Boris Boukhgalter, Talene Thomson, Zac Zwirko, Georgia Giannoukos, Michael C. Zody, Danni Zhong, Jason Blye, Stuart DeGray, Marc Azer, Robert D. Miller, Amr Abdouelleil, Brian Hurhula, Filip Rege, John Stalker, Andrew Barry, Pablo Alvarez, Norbu Dhargay, Krista Lance, Chris T. Amemiya, Jerilyn A. Walker, Jennifer R. Weidman, Peter An, Erin E. Dooley, William Lee, and Alville Collymore
- Subjects
Genetics ,Base Composition ,Genome evolution ,Genome ,Multidisciplinary ,Genomics ,Opossums ,Biology ,biology.organism_classification ,Polymorphism, Single Nucleotide ,Synteny ,Monodelphis domestica ,Evolution, Molecular ,X Chromosome Inactivation ,Opossum ,Molecular evolution ,Protein Biosynthesis ,DNA Transposable Elements ,Animals ,Humans ,Gene family ,Gene conversion ,Conserved Sequence - Abstract
We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
- Published
- 2007
- Full Text
- View/download PDF
12. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition
- Author
-
Kristin Anderka, Levi A. Garraway, Eva M. Goetz, Kristian Cibulskis, Zachary A. Cooper, Danielle Perrin, Aaron McKenna, Scott L. Carter, Ryan J. Sullivan, Mara Rosenberg, Jennifer A. Wargo, Keith T. Flaherty, Stacey Gabriel, Daniel J. Treacy, Eliezer M. Van Allen, Eran Hodis, Gregory V. Kryukov, Dennis C. Friedrich, Nikhil Wagle, Deborah N. Farlow, Dennie T. Frederick, Gad Getz, Cory M. Johannessen, Sheila Fisher, Amaro Taylor-Weiner, and Donald P. Lawrence
- Subjects
Trametinib ,MAPK/ERK pathway ,Kinase ,Melanoma ,Dabrafenib ,Mitogen-activated protein kinase kinase ,Biology ,medicine.disease ,Article ,Proto-Oncogene Proteins B-raf ,Oncology ,medicine ,Cancer research ,Protein kinase A ,medicine.drug - Abstract
Treatment of BRAF-mutant melanoma with combined dabrafenib and trametinib, which target RAF and the downstream MAP–ERK kinase (MEK)1 and MEK2 kinases, respectively, improves progression-free survival and response rates compared with dabrafenib monotherapy. Mechanisms of clinical resistance to combined RAF/MEK inhibition are unknown. We performed whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-seq) on pretreatment and drug-resistant tumors from five patients with acquired resistance to dabrafenib/trametinib. In three of these patients, we identified additional mitogen-activated protein kinase (MAPK) pathway alterations in the resistant tumor that were not detected in the pretreatment tumor, including a novel activating mutation in MEK2 (MEK2Q60P). MEK2Q60P conferred resistance to combined RAF/MEK inhibition in vitro, but remained sensitive to inhibition of the downstream kinase extracellular signal–regulated kinase (ERK). The continued MAPK signaling-based resistance identified in these patients suggests that alternative dosing of current agents, more potent RAF/MEK inhibitors, and/or inhibition of the downstream kinase ERK may be needed for durable control of BRAF-mutant melanoma. Significance: This study represents an initial clinical genomic study of acquired resistance to combined RAF/MEK inhibition in BRAF-mutant melanoma, using WES and RNA-seq. The presence of diverse resistance mechanisms suggests that serial biopsies and genomic/molecular profiling at the time of resistance may ultimately improve the care of patients with resistant BRAF-mutant melanoma by specifying tailored targeted combinations to overcome specific resistance mechanisms. Cancer Discov; 4(1); 61–8. ©2013 AACR. See related commentary by Solit and Rosen, p. 27 This article is highlighted in the In This Issue feature, p. 1
- Published
- 2013
13. A High-Throughput Chromatin Immunoprecipitation Approach Reveals Principles of Dynamic Gene Regulation in Mammals
- Author
-
Christine S. Cheng, Oren Ram, Brian Minie, Dennis C. Friedrich, Daniela Amann-Zalcenstein, Alon Goren, Chamutal Bornstein, James T. Robinson, Bang Wong, Mitchell Guttman, Andreas Gnirke, Sheila Fisher, Anne Thielke, Zohar Itzhaki, Assaf Weiner, Nir Yosef, James Meldrim, Ronnie Blecher-Gonen, Nir Friedman, Nir Hacohen, Raktima Raychowdhury, Bradley E. Bernstein, Manuel Garber, Ido Amit, Nicolas Chevrier, Aviv Regev, and Chad Nusbaum
- Subjects
Chromatin Immunoprecipitation ,Computational biology ,Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Transcriptional regulation ,Animals ,Molecular Biology ,Transcription factor ,ChIA-PET ,030304 developmental biology ,Genetics ,Regulation of gene expression ,0303 health sciences ,Cell Biology ,DNA ,Dendritic Cells ,ChIP-on-chip ,Chromatin ,ChIP-sequencing ,High-Throughput Screening Assays ,Gene Expression Regulation ,Chromatin immunoprecipitation ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
Understanding the principles governing mammalian gene regulation has been hampered by the difficulty in measuring in vivo binding dynamics of large numbers of transcription factors (TF) to DNA. Here, we develop a high-throughput Chromatin ImmunoPrecipitation (HT-ChIP) method to systematically map protein-DNA interactions. HT-ChIP was applied to define the dynamics of DNA binding by 25 TFs and 4 chromatin marks at 4 time-points following pathogen stimulus of dendritic cells. Analyzing over 180,000 TF-DNA interactions we find that TFs vary substantially in their temporal binding landscapes. This data suggests a model for transcription regulation whereby TF networks are hierarchically organized into cell differentiation factors, factors that bind targets prior to stimulus to prime them for induction, and factors that regulate specific gene programs. Overlaying HT-ChIP data on gene-expression dynamics shows that many TF-DNA interactions are established prior to the stimuli, predominantly at immediate-early genes, and identified specific TF ensembles that coordinately regulate gene-induction.
- Published
- 2012
14. Structure, function and diversity of the healthy human microbiome
- Author
-
Catherine A. Lozupone, Paul Spicer, Margaret Priest, Todd J. Treangen, Niall J. Lennon, Thomas M. Schmidt, Sandra W. Clifton, Ken Chu, Vandita Joshi, Catherine C. Davis, Omry Koren, Yuanqing Wu, Christie Kovar, Jonathan Friedman, Matthew D. Pearson, Scott T. Kelley, Brandi L. Cantarel, Patrick S. G. Chain, Chad Nusbaum, Jonathan Crabtree, Lu Wang, Bonnie P. Youmans, James A. Katancik, George M. Weinstock, Granger G. Sutton, Lisa Begg, Candace N. Farmer, Victor Felix, Barbara A. Methé, Elena Deych, Martin J. Blaser, Amy L. McGuire, Pamela McInnes, Xiang Qin, James Versalovic, James R. White, Yan Ding, Christian J. Buhay, Jason R. Miller, Susan M. Huse, Wm. Michael Dunne, Vivien Bonazzi, Jeremy Zucker, Ioanna Pagani, Robert C. Edgar, Dana A. Busam, Gina A. Simone, Michael Feldgarden, Vincent Magrini, Richard A. Gibbs, Noam J. Davidovics, Indresh Singh, Lucinda Fulton, Lucia Alvarado, Rob Knight, Emma Allen-Vercoe, Teena Mehta, Patricio S. La Rosa, Carsten Russ, Joshua Orvis, Sahar Abubucker, Jacques Ravel, Richard R. Sharp, Dirk Gevers, Wesley C. Warren, Pamela Sankar, Chad Tomlinson, Donna M. Muzny, Jean E. McEwen, Nihar U. Sheth, Sheila Fisher, Katherine H. Huang, Dennis C. Friedrich, Gary C. Armitage, John Martin, Richard K. Wilson, Katarzyna Wilczek-Boney, Catrina Fronick, Patrick Minx, Rebecca Truty, William D. Shannon, Matthew B. Scholz, Kris A. Wetterstrand, Maria Y. Giovanni, Katherine P. Lemon, Floyd E. Dewhirst, Shaila Chhibba, Anthony A. Fodor, Lan Zhang, Patrick D. Schloss, Lynn M. Schriml, Doyle V. Ward, Diana Tabbaa, Jose C. Clemente, Larry J. Forney, Kimberley D. Delehaunty, Cesar Arze, Sharvari Gujja, Lita M. Proctor, Christopher Smillie, Elizabeth L. Appelbaum, Konstantinos Liolios, Chandri Yandava, David J. Dooling, Emily L. Harris, Katherine S. Pollard, Clinton Howarth, Tatiana A. Vishnivetskaya, Sarah Young, Huaiyang Jiang, Karoline Faust, Janet K. Jansson, Kymberlie Hallsworth-Pepin, Owen White, Thomas J. Sharpton, Yiming Zhu, Yanjiao Zhou, Julia A. Segre, Jason Walker, Heidi H. Kong, Toby Bloom, Mathangi Thiagarajan, Tulin Ayvaz, I. Min A. Chen, Bo Liu, Kim C. Worley, Jennifer R. Wortman, Susan Kinder Haake, Manolito Torralba, Makedonka Mitreva, Kjersti Aagaard, J. Fah Sathirapongsasuti, Carolyn Deal, Jeroen Raes, Olukemi O. Abolude, Yue Liu, Rachel L. Erlich, Gary L. Andersen, Nicola Segata, Christopher Wellington, Todd Wylie, Kristine M. Wylie, Tsegahiwot Belachew, Jonathan H. Badger, Mark A. Watson, Aye Wollam, Zhengyuan Wang, Michelle G. Giglio, Kelvin Li, Diane E. Hoffmann, Cristyn Kells, Daniel D. Sommer, Victor M. Markowitz, Chien Chi Lo, Karen E. Nelson, Brian J. Haas, Ruth M. Farrell, Craig Pohl, Harindra Arachchi, Nicholas B. King, Gregory A. Buck, Konstantinos Mavromatis, Qiandong Zeng, Krishna Palaniappan, Kathie A. Mihindukulasuriya, Dan Knights, Anup Mahurkar, Nathalia Garcia, Mary A. Cutting, Theresa A. Hepburn, Mina Rho, Catherine Jordan, Christina Giblin, Dawn Ciulla, Shital M. Patel, Eric J. Alm, Kevin Riehle, Irene Newsham, Sarah K. Highlander, Jamison McCorrison, Nikos C. Kyrpides, Mircea Podar, Beltran Rodriguez-Mueller, Lora Lewis, Robert S. Fulton, Yuzhen Ye, Joseph L. Campbell, Laurie Zoloth, R. Dwayne Lunsford, Ramana Madupu, A. Scott Durkin, Maria C. Rivera, Sergey Koren, Shibu Yooseph, Ruth E. Ley, Erica Sodergren, Cecil M. Lewis, Heather Huot Creasy, Joseph F. Petrosino, Jacques Izard, Jack D. Sobel, J. Paul Brooks, Jeffrey G. Reid, Antonio Gonzalez, Narmada Shenoy, Elizabeth A. Lobos, Georgia Giannoukos, Matthew C. Ross, Allison D. Griggs, Yu-Hui Rogers, Leslie Foster, Wendy A. Keitel, Lei Chen, Alyxandria M. Schubert, Scott Anderson, Peter J. Mannon, Shane Canon, Hongyu Gao, Mihai Pop, Holli A. Hamilton, Tessa Madden, Michelle Oglaughlin, Karthik Kota, Monika Bihan, Veena Bhonagiri, Michael Holder, Daniel McDonald, Liang Ye, Sandra L. Lee, Rosamond Rhodes, Asif T. Chinwalla, Ashlee M. Earl, Shannon Dugan, Sean Conlan, Johannes B. Goll, Jonathan M. Goldberg, Valentina Di Francesco, Curtis Huttenhower, Brandi Herter, Todd Z. DeSantis, Sean M. Sykes, Michael Fitzgerald, Elaine R. Mardis, Jane Peterson, Bruce W. Birren, Ravi Sanka, Carl C. Baker, Jeffery A. Schloss, Massachusetts Institute of Technology. Computational and Systems Biology Program, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Civil and Environmental Engineering, Alm, Eric J., Friedman, Jonathan, and Smillie, Christopher S.
- Subjects
Adult ,Male ,Adolescent ,Ecology (disciplines) ,Biology ,Bioinformatics ,03 medical and health sciences ,Young Adult ,RNA, Ribosomal, 16S ,Humans ,Microbiome ,Ecosystem ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Bacteria ,030306 microbiology ,Gastrointestinal Microbiome ,Human microbiome ,Biodiversity ,Phenotype ,Evolutionary biology ,Health ,Earth Microbiome Project ,Metagenome ,Enterotype ,Female ,Oral Microbiome ,Metagenomics ,Metabolic Networks and Pathways ,Human Microbiome Project - Abstract
Author Manuscript date: 2013 February 05., Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
- Published
- 2012
15. A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries
- Author
-
Frank Juhn, Jillian Nolan, Chad Nusbaum, Robert Nicol, Alexander Allen, Geneva Young, Aaron M. Berlin, Andrew Barry, John Stalker, Sean M. Sykes, Jon Thompson, John Jarlath Walsh, Andrew Zimmer, Toni Delorey, Justin Abreu, Ramy Shammas, Sheila Fisher, Brian Minie, Lauren Ambrogio, Kristian Cibulskis, Zac Zwirko, Ryan Johnson, Dennis C. Friedrich, Brendan Blumenstiel, Timothy Fennell, Brian Reilly, and Stacey Gabriel
- Subjects
Quality Control ,Process (engineering) ,Method ,Biology ,Genome ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Exome ,Protocol (object-oriented programming) ,Throughput (business) ,030304 developmental biology ,Gene Library ,Oligonucleotide Array Sequence Analysis ,Genetics ,Automation, Laboratory ,0303 health sciences ,business.industry ,Genome, Human ,High-Throughput Nucleotide Sequencing ,Nucleic Acid Hybridization ,Automation ,Computer architecture ,030220 oncology & carcinogenesis ,Scalability ,Human genome ,business - Abstract
Genome targeting methods enable cost-effective capture of specific subsets of the genome for sequencing. We present here an automated, highly scalable method for carrying out the Solution Hybrid Selection capture approach that provides a dramatic increase in scale and throughput of sequence-ready libraries produced. Significant process improvements and a series of in-process quality control checkpoints are also added. These process improvements can also be used in a manual version of the protocol.
- Published
- 2010
16. Evolution of genes and genomes on the Drosophila phylogeny
- Author
-
Adam M. Phillippy, Edward Grandbois, Pen MacDonald, Iain MacCallum, Laura K. Reed, Wojciech Makalowski, Tracey Honan, Tania Tassinari Rieger, Melissa J. Hubisz, Josep M. Comeron, Douglas Smith, Jennifer Godfrey, Sebastian Strempel, Amr Abdouelleil, Brenton Gravely, Harindra Arachi, Albert J. Vilella, Marc Azer, Sarah A. Teichmann, Roger A. Hoskins, Corbin D. Jones, Keenan Ross, Derek Wilson, Stuart J. Newfeld, John Stalker, Thomas D. Watts, Dennis C. Friedrich, Therese A. Markow, Michael U. Mollenhauer, Tina Goode, Geneva Young, Terry Shea, Krista Lance, Karin A. Remington, Kevin A. Edwards, Lynne Aftuck, Cecil Rise, Sheridon Channer, Matthew D. Rasmussen, Nicole Stange-Thomann, Annie Lui, Robert A. Reenan, Todd Sparrow, Dave Begun, Tamrat Negash, Laura K. Sirot, Adrianne Brand, Adam Brown, Daisuke Yamamoto, Pema Phunkhang, Justin Abreu, Russell Schwartz, Ana Llopart, Abderrahim Farina, Kebede Maru, Chung-I Wu, Allen Alexander, Scott Anderson, So Jeong Lee, Jason Blye, Gary H. Karpen, Wilfried Haerty, Daniel A. Barbash, Peter Rogov, Barry O'Neill, Rachel Mittelman, Jakob Skou Pedersen, Leanne Hughes, Robert K. Bradley, Graziano Pesole, Wyatt W. Anderson, Anthony J. Greenberg, Alejandro Sánchez-Gracia, Julio Rozas, Stephen W. Schaeffer, Yama Thoulutsang, Roger K. Butlin, David H. Ardell, Stuart DeGray, Chris P. Ponting, Deborah E. Stage, Corrado Caggese, Montserrat Aguadé, Casey M. Bergman, Diallo Ferguson, Peili Zhang, Jeffrey R. Powell, Hajime Sato, Xiaohong Liu, Marta Sabariego Puig, Michael Parisi, Passang Dorje, Yoshihiko Tomimura, Adal Abebe, Carlo G. Artieri, Brian Hurhula, Filip Rege, Peter D. Keightley, Andrew Barry, Pablo Alvarez, Tsamla Tsamla, Marvin Wasserman, Santosh Jagadeeshan, Daniel L. Halligan, Chelsea D. Foley, Kim D. Delehaunty, Manfred Grabherr, Sourav Chatterji, Angela N. Brooks, James C. Costello, Mieke Citroen, James A. Yorke, Hsiao Pei Yang, Charles Chapple, Jian Lu, Carlos A. Machado, Norbu Dhargay, Tsering Wangchuk, Anat Caspi, Patrick Cahill, Tashi Bayul, Lisa Levesque, Otero L. Oyono, Atanas Mihalev, Dawa Thoulutsang, Dawn N. Abt, Sujaa Raghuraman, Manyuan Long, Maria Mendez-Lago, Charles Matthews, Kimberly Dooley, Alex Wong, Melanie A. Huntley, William R. Jeck, Ira Topping, Ben Kanga, José P. Abad, Ana Cristina Lauer Garcia, Brikti Abera, Kunsang Gyaltsen, Jonathan Butler, Alicia Franke, Michael C. Schatz, Cheewhye Chin, Charles F. Aquadro, Justin Johnson, Bryant F. McAllister, Georgia Giannoukos, M. Erii Husby, Rod A. Wing, Shangtao Liu, Jean L. Chang, Jennifer Daub, Eiko Kataoka, Leopold Parts, Rakela Lubonja, Margaret Priest, Yoshiko N. Tobari, Teena Mehta, Evgeny M. Zdobnov, Yeshi Lokyitsang, Richard Elong, Matthew J. Parisi, Louis Meneus, Eric S. Lander, Alan Filipski, Gary Gearin, Nabil Hafez, Nicholas Sisneros, David B. Jaffe, Ian Holmes, Marina Sirota, Leonid Boguslavskiy, Lisa Chuda, LaDeana W. Hillier, Meizhong Luo, Phil Batterham, Michael Kleber, Richard K. Wilson, Yama Cheshatsang, Qing Yu, Rebecca Reyes, Matthew W. Hahn, Andreas Heger, Mar Marzo, Patrick Minx, Kerstin Lindblad-Toh, Vera L. S. Valente, Adam Wilson, William C. Jordan, Mohamed A. F. Noor, Chiao-Feng Lin, Asha Kamat, Heather Ebling, Mihai Pop, Frances Letendre, Mariana F. Wolfner, Don Gilbert, Ngawang Sherpa, Riza M. Daza, Oana Mihai, Gabriel C. Wu, Aaron M. Berlin, Ewen F. Kirkness, Monika D. Huard, Robert S. Fulton, Randall H. Brown, Danni Zhong, Sharon Stavropoulos, Venky N. Iyer, Xu Mu, Christina R. Gearin, David M. Rand, Jerry A. Coyne, Dan Hultmark, Jill Falk, Christopher Patti, Montserrat Papaceit, James Meldrim, Valentine Mlenga, Muneo Matsuda, Sven Findeiß, Todd A. Schlenke, Kevin McKernan, Brian P. Walenz, Timothy B. Sackton, Leonardo Koerich, Peter An, Robert Nicol, Chuong B. Do, Dmitry Khazanovich, Carmen Segarra, Maura Costello, St Christophe Acer, Claudia Rohde, Serafim Batzoglou, Hadi Quesneville, Evan Mauceli, Andy Vo, Luciano M. Matzkin, Susan E. Celniker, Patrick M. O’Grady, William M. Gelbart, Lloyd Low, Jamal Abdulkadir, Jessica Spaulding, Brian R. Calvi, Charlotte Henson, Robert David, Jennifer L. Hall, Andrew G. Clark, Anastasia Gardiner, Susan M. Russo, Birhane Hagos, Kerri Topham, Amy Denise Reily, Eli Venter, Jerome Naylor, Sandra W. Clifton, Valer Gotea, Samuel R. Gross, Manolis Kellis, Claude Bonnet, Christopher Strader, Tashi Lokyitsang, Nyima Norbu, Jennifer Baldwin, Stephen M. Mount, Robert L. Strausberg, Shailendra Yadav, Kristipati Ravi Ram, Steven L. Salzberg, Erik Gustafson, David A. Garfield, Eva Freyhult, Arthur L. Delcher, Enrico Blanco, Granger G. Sutton, Jason M. Tsolas, Charles Robin, Angie S. Hinrichs, Christopher D. Smith, Jane Wilkinson, Brendan McKernan, Fritz Pierre, William McCusker, Brian Oliver, Barry E. Garvin, Sudhir Kumar, Peter Kisner, Kunsang Dorjee, A. Bernardo Carvalho, Anna Montmayeur, Andrew Zimmer, Diana Shih, Wei Tao, Shiaw Pyng Yang, Sante Gnerre, Sampath Settipalli, Thu Nguyen, Paolo Barsanti, Brian P. Lazzaro, Sonja J. Prohaska, J. Craig Venter, Senait Tesfaye, Susan McDonough, Kim D. Pruitt, Alexander Stark, Sergio Castrezana, Lucinda Fulton, Richard T. Lapoint, Greg Gibson, John Spieth, Boris Adryan, Georgius De Haan, Sheila Fisher, Daniel A. Pollard, Seva Kashin, Rob J. Kulathinal, Michael B. Eisen, Nathaniel Novod, Christina Demaso, Alan Dupes, Amanda M. Larracuente, Toby Bloom, Alfredo Villasante, Charles H. Langley, Rama S. Singh, Niall J. Lennon, Kristi L. Montooth, Daniel Barker, Wolfgang Stephan, David Sturgill, Ruiqiang Li, Andrew Hollinger, Boris Boukhgalter, Talene Thomson, Patrick Cooke, Zac Zwirko, Nadia D. Singh, Michael Weiand, Lior Pachter, Roderic Guigó, Yu Zhang, Jay D. Evans, Stephanie Bosak, Rosie Levine, Lu Shi, Kiyohito Yoshida, Carolyn S. McBride, Pouya Kheradpour, William Brockman, Alberto Civetta, Hiroshi Akashi, Marcia Lara, Susan Faro, Sam Griffiths-Jones, Michael R. Brent, Thomas H. Eickbush, Gane Ka-Shu Wong, Elizabeth P. Ryan, Erica Anderson, Roberta Kwok, Asif T. Chinwalla, Sahal Osman, Nga Nguyen, Damiano Porcelli, Missole Doricent, Saverio Vicario, Marc Rubenfield, Bárbara Negre, Gillian M. Halter, Erin E. Dooley, Elena R. Lozovsky, William Lee, Alville Collymore, Catherine Stone, Tanya Mihova, Jun Wang, Karsten Kristiansen, Imane Bourzgui, Michael F. Lin, Katie D'Aco, Filipe G. Vieira, Choe Norbu, Yu-Hui Rogers, Aaron L. Halpern, Eugene W. Myers, Sharleen Grewal, Robert T. Good, Alfredo Ruiz, Dave Kudrna, Joseph Graham, Alex Lipovsky, Leonidas Mulrain, Tsering Wangdi, Roman Arguello, Mira V. Han, Arjun Bhutkar, Rasmus Nielsen, David J. Saranga, Aleksey V. Zimin, Vasilia Magnisalis, Helen Vassiliev, Thomas C. Kaufman, Eva Markiewicz, Temple F. Smith, Jinlei Liu, Loryn Gadbois, Michael G. Ritchie, Lisa Zembek, Daniel Bessette, Pasang Bachantsang, Adam Navidi, Department of Molecular Biology and Genetics, Cornell University [New York], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), University of California [Berkeley], University of California, Agencourt Bioscience Corporation, Partenaires INRAE, Faculty of Life Science, University of Manchester [Manchester], Laboratory of Cellular and Developmental Biology (LCDB), NIDDK, NIH, Department of Ecology and Evolutionary Biology, University of Arizona, Department of Biology, Indiana University [Bloomington], Indiana University System-Indiana University System, Massachusetts Institute of Technology (MIT), Harvard University [Cambridge], Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Brown University, Laboratory of Molecular Biology, Medical Research Council, Departament de Genetica, Universitat de Barcelona (UB), Pennsylvania State University (Penn State), Penn State System-Penn State System, Department of Genetics, University of Georgia [USA], Uppsala University, Department of Ecology and Evolution [Lausanne], Université de Lausanne (UNIL), McMaster University, School of Biology, IE University, Università degli Studi di Bari Aldo Moro, University of Melbourne, Stanford University, University of California [Davis] (UC Davis), Boston University [Boston] (BU), Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Washington University in Saint Louis (WUSTL), University of Sheffield, Syracuse University, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Department of Bioengineering, Beihang University (BUAA), Tucson Stock Center, Genome Center, University of California-University of California, Genome Sequencing Center, University of Washington School of Medicine, University of Winnipeg, Iowa State University (ISU), Indiana University System, The Wellcome Trust Sanger Institute [Cambridge], Center for Bioinformatics and Computational Biology, University of Delaware [Newark], Illinois State University, University of Rochester [USA], United States Department of Agriculture (USDA), Arizona State University [Tempe] (ASU), Leipzig University, Universidade Federal do Rio Grande do Sul (UFRGS), Duke University, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of Connecticut (UCONN), Computer Science Département, Université Saint-Esprit de Kaslik (USEK), Mc Master University, Indiana University, Institute of Evolutionary Biology, University of Edinburgh, J. Craig Venter Institute [La Jolla, USA] (JCVI), University of Oxford [Oxford], Center for Biomolecular Science and Engineering, Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), and Zdobnov, Evgeny
- Subjects
melanogaster genome ,0106 biological sciences ,RNA, Untranslated ,[SDV]Life Sciences [q-bio] ,Genome, Insect ,RNA, Untranslated/genetics ,Genes, Insect ,01 natural sciences ,Genome ,Genome, Insect/ genetics ,Gene Order ,Genome, Mitochondrial/genetics ,Drosophila Proteins ,Phylogeny ,ddc:616 ,Genetics ,0303 health sciences ,Multidisciplinary ,biology ,Reproduction ,Genomics ,Multigene Family/genetics ,Reproduction/genetics ,DNA Transposable Elements/genetics ,Genes, Insect/ genetics ,Multigene Family ,dosage compensation ,Drosophila ,amino-acid substitution ,Drosophila Protein ,Drosophila Proteins/genetics ,Synteny/genetics ,fruit-fly ,010603 evolutionary biology ,Synteny ,Drosophila sechellia ,Evolution, Molecular ,03 medical and health sciences ,Phylogenetics ,Molecular evolution ,Codon/genetics ,[SDV.BV]Life Sciences [q-bio]/Vegetal Biology ,Animals ,adaptive protein evolution ,Codon ,030304 developmental biology ,Gene Order/genetics ,molecular evolution ,fungi ,Immunity ,synonymous codon usage ,Sequence Analysis, DNA ,Immunity/genetics ,biology.organism_classification ,Drosophila mojavensis ,Evolutionary biology ,Genome, Mitochondrial ,DNA Transposable Elements ,maximum-likelihood ,noncoding dna ,Drosophila/ classification/ genetics/immunology/metabolism ,Sequence Alignment ,natural-selection ,Drosophila yakuba - Abstract
Affiliations des auteurs : cf page 216 de l'article; International audience; Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
- Published
- 2007
- Full Text
- View/download PDF
17. Genome sequence, comparative analysis and haplotype structure of the domestic dog
- Author
-
Tsering Wangchuk, Mayank Kumar, Sharon Stavropoulos, James Cuff, Mostafa Benamara, David DeCaprio, Birhane Hagos, Nathaniel Novod, Tashi Lokyitsang, Nyima Norbu, Jennifer Baldwin, Sabrina M. Stone, Catherine Stone, Geneva Young, Osebhajajeme Egbiremolen, Dawa Thoulutsang, Tanya Mihova, Lisa Kim, Julie Sahalie, Jan Macdonald, Amr Abouelleil, Toby Bloom, Yama Cheshatsang, Carolyne Bardeleben, Qing Yu, Berta Blitshteyn, Tuyen T. Nguyen, Tarjei S. Mikkelsen, Edward Grandbois, Claire M. Wade, John E. Major, Filip Rege, Cindy Nguyen, Andrew Barry, Tracey Honan, Pablo Alvarez, Andy Vo, Manuel Garber, Cristyn Kells, Rachel Mittelman, Lucien Oyono, Norbu Dhargay, Sean M. Sykes, Diallo Ferguson, Tyler Aldredge, Tenchoe Nyima, Todd Sparrow, Daniel S. Hagopian, Christophe Hitte, Andreas Heger, Jane E. Wilkinson, Verneda Ray, Peter Rogov, Ewen F. Kirkness, Jill Falk, Robert Nicol, Christopher Patti, Danielle Perrin, Ted Sharpe, Douglas Smith, Peter Olandt, Matthew Breen, Ali Aslam, Cherylyn Smith, Tara Biagi, Diane Gage, Jean L. Chang, Karen Hughes Miller, Valentine Mlenga, Andrea Horn, Jessie Sloan, Claire M. Healy, Adam Wilson, Ngawang Sherpa, Riza M. Daza, David B. Jaffe, Leonid Boguslavskiy, Jody Camarata, Peter Kisner, William H. Lee, Kunsang Dorjee, M. Husby, Sante Gnerre, Kunsang Gyaltsen, Asha Kamat, Jonathan Butler, Terrance Shea, Alicia Franke, Patrick Cooke, Rayale Rameau, Andrew Zimmer, Gary Gearin, Nabil Hafez, Kerri Topham, Kebede Maru, Chris P. Ponting, Jerome Naylor, Yama Thoulutsang, Keith O'Neill, Jinlei Liu, Manolis Kellis, Claude Bonnet, Claudel Antoine, Passang Dorje, Adal Abebe, Tsamla Tsamla, Michael Kleber, Michael Weiand, Audra Goyette, Rachael Thomas, Lisa Zembek, Atanas Mihalev, Daniel Bessette, Helen Vassiliev, Pasang Bachantsang, Adam Navidi, Kathleen Dooley, Caleb Webber, Pierre Tchuinga, Tashi Bayul, Michael Kamal, Heidi G. Parker, Ben Kanga, Kimberly Dooley, Nadia Calixte, Mostafa Ait-zahra, Niall J. Lennon, Ira Topping, Eric S. Lander, Pieter J. deJong, Nicole R. Allen, Peter An, Boris Boukhgalter, Richard Elong, Thomas E. Landers, Anthony Rachupka, Michael Fitzgerald, Lisa Leuper, William Brockman, Marcia Lara, Susan Faro, Elaine A. Ostrander, Joanne Zainoun, Leigh Anne Hunnicutt, Mark J. Daly, Leanne Hughes, April Cook, Patrick Cahill, Sujaa Raghuraman, Manfred Grabherr, Robert K. Wayne, Adam Brown, Xiaohong Liu, Charles Matthews, Scott Anderson, Margaret Priest, Shailendra Yadav, Evan Mauceli, Kerstin Lindblad-Toh, Patricia Ferreira, Yeshi Lokyitsang, Harindra Arachchi, Alexandre Melnikov, Christina Raymond, James Meldrim, Dmitry Khazanovich, Mieke Citroen, Aaron M. Berlin, Alix Chinh Kieu, John Stalker, Francis Galibert, Noah Duffey, Krista Lance, Louis Meneus, Jennifer Ruth Sadler Hall, Choe Norbu, Pema Tenzing, Richard Marabella, Chee-Wye Chin, Karen Foley, Xiaoping Yang, Nga Nguyen, Tenzin Dawoe, Ryan Hegarty, Julie Rogers, Joseph Graham, Chelsea D. Foley, Leonidas Mulrain, Tsering Wangdi, Karin Decktor, Sarah LeVine, Shuli Yang, Dennis C. Friedrich, Tina Goode, Cecil Rise, Teena Mehta, Laura Ayotte, Michele Clamp, Nicole Stange-Thomann, Annie Lui, Edward J. Kulbokas, Pema Phunkhang, Alan Dupes, Elinor K. Karlsson, Lynne Aftuck, Sahal Osman, Abderrahim Farina, Barry O'Neill, Diana M. Shih, Xiaohui Xie, Lester Dorris, Vijay Venkataraman, Benjamin Jester, Sampath Settipalli, Thu Nguyen, Alville Collymore, Klaus-Peter Koepfli, Senait Tesfaye, Nathan Houde, Susan McDonough, Leo Goodstadt, Glen Munson, Georgia Giannoukos, Jeffrey Chu, Nathan B. Sutter, Sheila A. Fisher, Charlien Jones, Michael C. Zody, Jianying Shi, John P. Pollinger, Mechele Sheehan, Stephen M. J. Searle, Fritz Pierre, Jason Blye, Jean-Pierre Leger, and Stuart DeGray
- Subjects
Male ,Genomics ,Single-nucleotide polymorphism ,Biology ,Genome ,Polymorphism, Single Nucleotide ,Synteny ,Conserved sequence ,Evolution, Molecular ,Mice ,Dogs ,Molecular evolution ,Animals ,Humans ,Dog Diseases ,Conserved Sequence ,Short Interspersed Nucleotide Elements ,Genetics ,Whole genome sequencing ,Multidisciplinary ,Dog leukocyte antigen ,Haplotype ,Rats ,Haplotypes ,Mutagenesis ,biology.protein ,Hybridization, Genetic ,Female - Abstract
Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
- Published
- 2005
18. Abstract 3152: CanSeq: prospective clinical whole-exome sequencing of FFPE tumor samples
- Author
-
Dennis C. Friedrich, Stacy W. Gray, Steven Joffe, Laura E. MacConaill, Danielle Perrin, Stacey Gabriel, Eliezer M. Van Allen, Daniel Auclair, Barrett J. Rollins, P.W. Kantoff, Nikhil Wagle, Judy Garber, Lauren Ambrogio, Sheila Fisher, Neal I. Lindeman, Gregory V. Kryukov, Levi A. Garraway, Gad Getz, and Pasi A. Jänne
- Subjects
Cancer Research ,biology ,business.industry ,PDGFRA ,Bioinformatics ,medicine.disease_cause ,Clinical trial ,Germline mutation ,Oncology ,CDKN2A ,biology.protein ,Medicine ,PTEN ,KRAS ,business ,Genotyping ,Exome sequencing - Abstract
INTRODUCTION: Knowledge of tumor genomic alterations that may predict therapeutic responses represents a growing clinical need. Although there has been an increase in the use of hotspot genotyping and targeted sequencing panels of small numbers of genes, the use of clinical whole exome sequencing (WES) remains underdeveloped. Prospective WES in cancer patients presents several logistical and scientific challenges, including (i) generating robust sequencing data from small amounts of FFPE tumor tissue, (ii) establishing a clinically relevant turnaround time, (iii) achieving clinical interpretation of genomic alterations, and (iv) communicating results to the clinical team and patients. Here, we describe CanSeq, a clinical WES platform to detect genomic alterations in FFPE tumor samples and identify clinically actionable and biologically meaningful alterations in order to aid clinical decision-making and inform future research. METHODS: We performed prospective WES on tumor and germline DNA from patients with advanced refractory cancer. Sequencing was performed at the Broad Institute using the Illumina HiSeq, starting with 100 ng of DNA or less from FFPE tumor tissue and matched normal blood. Data were analyzed using a novel algorithm to highlight clinically actionable mutations, indels, and copy number alterations. These were annotated and assigned levels of evidence, and an interactive web-based report was generated for review by clinicians. RESULTS: The average turnaround time from sample receipt to data delivery was 16 days. Each tumor sample was sequenced at 90X or greater depth of coverage with more than 80% of exons with at least 30X coverage. Analysis of the first 15 patients revealed at least one plausibly actionable somatic mutation in 14 samples. These alterations include “standard of care” alterations (BRAF, EGFR), entry criteria for clinical trials (PIK3CA, KRAS, PTEN), potentially actionable alterations based on more limited evidence (STK11, ATM, CRKL, CTNNB1, PDGFRA, CDK4, CDKN2A, SMARCB1, TP53), and alterations that were theoretically targetable (JAK3, SYK). Additional biologically relevant somatic alterations and notable germline alterations were also identified. For several patients, actionable alterations were confirmed in a CLIA lab and impacted clinical decision-making, including enrollment in clinical trials. CONCLUSION: We have developed a prospective clinical WES platform to robustly detect genomic alterations in archival FFPE tumor samples (using Citation Format: Nikhil Wagle, Eliezer Van Allen, Danielle Perrin, Dennis Friedrich, Sheila Fisher, Gregory Kryukov, Lauren Ambrogio, Daniel Auclair, Stacy Gray, Steven Joffe, Pasi Janne, Judy Garber, Laura Macconaill, Neal Lindeman, Barrett Rollins, Phillip Kantoff, Gad Getz, Stacey Gabriel, Levi A. Garraway. CanSeq: prospective clinical whole-exome sequencing of FFPE tumor samples. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3152. doi:10.1158/1538-7445.AM2013-3152
- Published
- 2013
- Full Text
- View/download PDF
19. Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation
- Author
-
Maura Costello, Sharon Kim, Stacey Gabriel, Sheila Fisher, Eric S. Lander, Danielle Perrin, Gad Getz, Dennis C. Friedrich, Jennifer L. Fostel, Trevor J. Pugh, Lee Lichtenstein, James Meldrim, Danielle Dionne, Timothy Fennell, Chip Stewart, Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.
- Subjects
Guanine ,DNA damage ,Genomics ,Biology ,medicine.disease_cause ,DNA sequencing ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,law ,Genetics ,medicine ,Humans ,Transversion ,Melanoma ,Alleles ,Polymerase chain reaction ,030304 developmental biology ,0303 health sciences ,Mutation ,High-Throughput Nucleotide Sequencing ,DNA ,Sequence Analysis, DNA ,DNA extraction ,chemistry ,030220 oncology & carcinogenesis ,Methods Online ,Artifacts ,Oxidation-Reduction ,DNA Damage - Abstract
As researchers begin probing deep coverage sequencing data for increasingly rare mutations and subclonal events, the fidelity of next generation sequencing (NGS) laboratory methods will become increasingly critical. Although error rates for sequencing and polymerase chain reaction (PCR) are well documented, the effects that DNA extraction and other library preparation steps could have on downstream sequence integrity have not been thoroughly evaluated. Here, we describe the discovery of novel C > A/G > T transversion artifacts found at low allelic fractions in targeted capture data. Characteristics such as sequencer read orientation and presence in both tumor and normal samples strongly indicated a non-biological mechanism. We identified the source as oxidation of DNA during acoustic shearing in samples containing reactive contaminants from the extraction process. We show generation of 8-oxoguanine (8-oxoG) lesions during DNA shearing, present analysis tools to detect oxidation in sequencing data and suggest methods to reduce DNA oxidation through the introduction of antioxidants. Further, informatics methods are presented to confidently filter these artifacts from sequencing data sets. Though only seen in a low percentage of reads in affected samples, such artifacts could have profoundly deleterious effects on the ability to confidently call rare mutations, and eliminating other possible sources of artifacts should become a priority for the research community., National Human Genome Research Institute (U.S.) (HG03067-05)
- Published
- 2013
- Full Text
- View/download PDF
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.