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1. de novo variant calling identifies cancer mutation signatures in the 1000 Genomes Project

Author

Jeffrey K. Ng, Pankaj Vats, Elyn Fritz‐Waters, Stephanie Sarkar, Eleanor I. Sams, Evin M. Padhi, Zachary L. Payne, Shawn Leonard, Marc A. West, Chandler Prince, Lee Trani, Marshall Jansen, George Vacek, Mehrzad Samadi, Timothy T. Harkins, Craig Pohl, and Tychele N. Turner

Subjects
Genetics, Genetics (clinical)
Abstract

Detection of de novo variants (DNVs) is critical for studies of disease-related variation and mutation rates. To accelerate DNV calling, we developed a graphics processing units-based workflow. We applied our workflow to whole-genome sequencing data from three parent-child sequenced cohorts including the Simons Simplex Collection (SSC), Simons Foundation Powering Autism Research (SPARK), and the 1000 Genomes Project (1000G) that were sequenced using DNA from blood, saliva, and lymphoblastoid cell lines (LCLs), respectively. The SSC and SPARK DNV callsets were within expectations for number of DNVs, percent at CpG sites, phasing to the paternal chromosome of origin, and average allele balance. However, the 1000G DNV callset was not within expectations and contained excessive DNVs that are likely cell line artifacts. Mutation signature analysis revealed 30% of 1000G DNV signatures matched B-cell lymphoma. Furthermore, we found variants in DNA repair genes and at Clinvar pathogenic or likely-pathogenic sites and significant excess of protein-coding DNVs in IGLL5; a gene known to be involved in B-cell lymphomas. Our study provides a new rapid DNV caller for the field and elucidates important implications of using sequencing data from LCLs for reference building and disease-related projects.

Published
2022

2. Author Correction: Comparative and demographic analysis of orang-utan genomes

Author

Devin P. Locke, LaDeana W. Hillier, Wesley C. Warren, Kim C. Worley, Lynne V. Nazareth, Donna M. Muzny, Shiaw-Pyng Yang, Zhengyuan Wang, Asif T. Chinwalla, Pat Minx, Makedonka Mitreva, Lisa Cook, Kim D. Delehaunty, Catrina Fronick, Heather Schmidt, Lucinda A. Fulton, Robert S. Fulton, Joanne O. Nelson, Vincent Magrini, Craig Pohl, Tina A. Graves, Chris Markovic, Andy Cree, Huyen H. Dinh, Jennifer Hume, Christie L. Kovar, Gerald R. Fowler, Gerton Lunter, Stephen Meader, Andreas Heger, Chris P. Ponting, Tomas Marques-Bonet, Can Alkan, Lin Chen, Ze Cheng, Jeffrey M. Kidd, Evan E. Eichler, Simon White, Stephen Searle, Albert J. Vilella, Yuan Chen, Paul Flicek, Jian Ma, Brian Raney, Bernard Suh, Richard Burhans, Javier Herrero, David Haussler, Rui Faria, Olga Fernando, Fleur Darré, Domènec Farré, Elodie Gazave, Meritxell Oliva, Arcadi Navarro, Roberta Roberto, Oronzo Capozzi, Nicoletta Archidiacono, Giuliano Della Valle, Stefania Purgato, Mariano Rocchi, Miriam K. Konkel, Jerilyn A. Walker, Brygg Ullmer, Mark A. Batzer, Arian F. A. Smit, Robert Hubley, Claudio Casola, Daniel R. Schrider, Matthew W. Hahn, Victor Quesada, Xose S. Puente, Gonzalo R. Ordoñez, Carlos López-Otín, Tomas Vinar, Brona Brejova, Aakrosh Ratan, Robert S. Harris, Webb Miller, Carolin Kosiol, Heather A. Lawson, Vikas Taliwal, André L. Martins, Adam Siepel, Arindam RoyChoudhury, Xin Ma, Jeremiah Degenhardt, Carlos D. Bustamante, Ryan N. Gutenkunst, Thomas Mailund, Julien Y. Dutheil, Asger Hobolth, Mikkel H. Schierup, Oliver A. Ryder, Yuko Yoshinaga, Pieter J. de Jong, George M. Weinstock, Jeffrey Rogers, Elaine R. Mardis, Richard A. Gibbs, and Richard K. Wilson

Subjects
Multidisciplinary
Published
2022
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3. de novo variant calling identifies cancer mutation profiles in the 1000 Genomes Project

Author

Jeffrey K. Ng, Pankaj Vats, Elyn Fritz-Waters, Stephanie Sarkar, Eleanor I. Sams, Evin M. Padhi, Zachary L. Payne, Shawn Leonard, Marc A. West, Chandler Prince, Lee Trani, Marshall Jansen, George Vacek, Mehrzad Samadi, Timothy T. Harkins, Craig Pohl, and Tychele N. Turner

Subjects
Mutation rate, Lymphoblastoid cell, CpG site, Mutation (genetic algorithm), medicine, Cancer, Computational biology, Biology, 1000 Genomes Project, medicine.disease, Genome
Abstract

Detection of de novo variants (DNVs) is critical for studies of disease-related variation and mutation rates. We developed a GPU-based workflow to rapidly call DNVs (HAT) and demonstrated its effectiveness by applying it to 4,216 Simons Simplex Collection (SSC) whole-genome sequenced parent-child trios from DNA derived from blood. In our SSC DNV data, we identified 78 ± 15 DNVs per individual, 18% ± 5% at CpG sites, 75% ± 9% phased to the paternal chromosome of origin, and an average allele balance of 0.49. These calculations are all in line with DNV expectations. We sought to build a control DNV dataset by running HAT on 602 whole-genome sequenced parent-child trios from DNA derived from lymphoblastoid cell lines (LCLs) from the publicly available 1000 Genomes Project (1000G). In our 1000G DNV data, we identified 740 ± 967 DNVs per individual, 14% ± 4% at CpG sites, 61% ± 11% phased to the paternal chromosome of origin, and an average allele balance of 0.41. Of the 602 trios, 80% had > 100 DNVs and we hypothesized the excess DNVs were cell line artifacts. Several lines of evidence in our data suggest that this is true and that 1000G does not appear to be a static reference. By mutation profile analysis, we tested whether these cell line artifacts were random and found that 40% of individuals in 1000G did not have random DNV profiles; rather they had DNV profiles matching B-cell lymphoma. Furthermore, we saw significant excess of protein-coding DNVs in 1000G in the gene IGLL5 that has already been implicated in this cancer. As a result of cell line artifacts, 1000G has variants present in DNA repair genes and at Clinvar pathogenic or likely-pathogenic sites. Our study elucidates important implications of the use of sequencing data from LCLs for both reference building projects as well as disease-related projects whereby these data are used in variant filtering steps.

Published
2021
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4. 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

5. Genome Remodeling in a Basal-like Breast Cancer Metastasis and Xenograft

Author

Ken Chen, Adam F. Dukes, Chris Harris, Mark D. Mason, Elizabeth L. Appelbaum, Jennifer Ivanovich, Justin T. Lolofie, Michael D. McLellan, Lei Chen, Benjamin J. Oberkfell, Lisa Cook, Jeremy Hoog, Devin P. Locke, Shunqiang Li, Jennifer S. Hodges, Scott M. Smith, Feiyu Du, Dong-Wei Shen, Amy Hawkins, Gabriel E. Sanderson, Rachel Abbott, Lucinda Fulton, John W. Wallis, Mark A. Watson, Sherri R. Davies, George M. Weinstock, Michelle D O'Laughlin, Richard K. Wilson, Joelle Kalicki, Jacqueline E. Snider, Joshua F. McMichael, Charles M. Perou, Heather K. Schmidt, Nathan D. Dees, Tammi L. Vickery, Jerry S. Reed, Glendoria Elliott, Robert S. Fulton, William Schierding, Li-li Lin, Robert J. Crowder, Timothy J. Ley, James M. Eldred, Josh B. Peck, Craig Pohl, Dominic M. Thompson, David J. Dooling, Paul J. Goodfellow, Michael C. Wendl, Vincent Magrini, Therese Guintoli, Katherine DeSchryver, Li Ding, Kelly E. Bernard, Kim D. Delehaunty, David E. Larson, Qunyuan Zhang, Kimberley A. Pape, Mark L. Cunningham, Matthew J. Ellis, Madeline E. Wiechert, Sean McGrath, Rebecca Aft, Ling Lin, Elaine R. Mardis, Jody S. Robinson, Catrina Fronick, Yu Long Tao, and Daniel C. Koboldt

Subjects
Adult, DNA Copy Number Variations, DNA Mutational Analysis, Transplantation, Heterologous, Breast Neoplasms, Biology, Bioinformatics, medicine.disease_cause, Translocation, Genetic, Article, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Gene Frequency, medicine, Humans, 030304 developmental biology, 0303 health sciences, Mutation, Multidisciplinary, Brain Neoplasms, Genome, Human, Cancer, Genomics, Cell cycle, medicine.disease, Transplantation, 030220 oncology & carcinogenesis, Disease Progression, Cancer research, Human genome, Female, alpha Catenin, Neoplasm Transplantation, Brain metastasis
Abstract

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumor progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumor, a brain metastasis, and a xenograft derived from the primary tumor. The metastasis contained two de novo mutations and a large deletion not present in the primary tumor, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumor mutations, and displayed a mutation enrichment pattern that paralleled the metastasis (16 of 20 genes). Two overlapping large deletions, encompassing CTNNA1, were present in all three tumor samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared to the primary tumor suggest that secondary tumors may arise from a minority of cells within the primary.

Published
2010

6. BreakDancer: an algorithm for high-resolution mapping of genomic structural variation

Author

Qunyuan Zhang, Ken Chen, David E. Larson, Robert S. Fulton, Li Ding, Sean McGrath, Devin P. Locke, Richard K. Wilson, Elaine R. Mardis, Timothy J. Ley, John W. Wallis, Craig Pohl, Michael C. Wendl, Joelle Kalicki, Xiaoqi Shi, and Michael D. McLellan

Subjects
Base pair, Sequence analysis, Genomic Structural Variation, High resolution, Genomics, Computational biology, Biology, Biochemistry, Genome, Article, 03 medical and health sciences, 0302 clinical medicine, Genetic variation, Humans, Computer Simulation, Molecular Biology, 030304 developmental biology, Genetics, 0303 health sciences, Base Sequence, Genome, Human, Genetic Variation, DNA, Sequence Analysis, DNA, Cell Biology, 3. Good health, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Human genome, Algorithms, Biotechnology
Abstract

Detection and characterization of genomic structural variation are important for understanding the landscape of genetic variation in human populations and in complex diseases such as cancer. Recent studies demonstrate the feasibility of detecting structural variation using next-generation, short-insert, paired-end sequencing reads. However, the utility of these reads is not entirely clear, nor are the analysis methods with which accurate detection can be achieved. The algorithm BreakDancer predicts a wide variety of structural variants including insertion-deletions (indels), inversions and translocations. We examined BreakDancer's performance in simulation, in comparison with other methods and in analyses of a sample from an individual with acute myeloid leukemia and of samples from the 1,000 Genomes trio individuals. BreakDancer sensitively and accurately detected indels ranging from 10 base pairs to 1 megabase pair that are difficult to detect via a single conventional approach.

Published
2009
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7. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome

Author

Bob Fulton, Scott Abbott, Lisa Cook, Tracie L. Miner, Yu Zhao, Jacqueline E. Payton, David E. Larson, Rhonda E. Ries, Mark A. Watson, Scott M. Smith, Vincent Magrini, John F. DiPersio, Peter Westervelt, Brian H. Dunford-Shore, Sean McGrath, Jennifer Ivanovich, Michael D. McLellan, Matthew J. Walter, Nathan Sander, Timothy J. Ley, Craig Pohl, Matthew T. Hickenbotham, Jarret Glasscock, Daniel C. Koboldt, Amy Hawkins, Devin P. Locke, Rakesh Nagarajan, David Gordon, Li Ding, William D. Shannon, Elaine R. Mardis, Michael H. Tomasson, LaDeana W. Hillier, Ken Chen, Daniel C. Link, Richard K. Wilson, Patrick Minx, John R. Osborne, Sharon Heath, Rachel Abbott, Lucinda Fulton, Joshua J. Conyers, Asif T. Chinwalla, David J. Dooling, Timothy A. Graubert, Todd Wylie, Jack Baty, and Xiaoqi Shi

Subjects
Myeloid, Genomics, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, Genome, Article, DNA sequencing, Recurrence, medicine, Humans, Sequence Deletion, Skin, Genetics, Multidisciplinary, Genome, Human, Gene Expression Profiling, Sequence Analysis, DNA, Gene Expression Regulation, Neoplastic, Gene expression profiling, Leukemia, Myeloid, Acute, Mutagenesis, Insertional, Haematopoiesis, medicine.anatomical_structure, Case-Control Studies, Mutation, Disease Progression, Human genome, Carcinogenesis
Abstract

Lay Summary Acute myeloid leukemia is a highly malignant hematopoietic tumor that affects about 13,000 adults yearly in the United States. The treatment of this disease has changed little in the past two decades, since most of the genetic events that initiate the disease remain undiscovered. Whole genome sequencing is now possible at a reasonable cost and timeframe to utilize this approach for unbiased discovery of tumor-specific somatic mutations that alter the protein-coding genes. Here we show the results obtained by sequencing a typical acute myeloid leukemia genome and its matched normal counterpart, obtained from the patient’s skin. We discovered 10 genes with acquired mutations; two were previously described mutations thought to contribute to tumor progression, and 8 were novel mutations present in virtually all tumor cells at presentation and relapse, whose function is not yet known. Our study establishes whole genome sequencing as an unbiased method for discovering initiating mutations in cancer genomes, and for identifying novel genes that may respond to targeted therapies. We used massively parallel sequencing technology to sequence the genomic DNA of tumor and normal skin cells obtained from a patient with a typical presentation of FAB M1 Acute Myeloid Leukemia (AML) with normal cytogenetics. 32.7-fold ‘haploid’ coverage (98 billion bases) was obtained for the tumor genome, and 13.9-fold coverage (41.8 billion bases) was obtained for the normal sample. Of 2,647,695 well-supported Single Nucleotide Variants (SNVs) found in the tumor genome, 2,588,486 (97.7%) also were detected in the patient’s skin genome, limiting the number of variants that required further study. For the purposes of this initial study, we restricted our downstream analysis to the coding sequences of annotated genes: we found only eight heterozygous, non-synonymous somatic SNVs in the entire genome. All were novel, including mutations in protocadherin/cadherin family members (CDH24 and PCLKC), G-protein coupled receptors (GPR123 and EBI2), a protein phosphatase (PTPRT), a potential guanine nucleotide exchange factor (KNDC1), a peptide/drug transporter (SLC15A1), and a glutamate receptor gene (GRINL1B). We also detected previously described, recurrent somatic insertions in the FLT3 and NPM1 genes. Based on deep readcount data, we determined that all of these mutations (except FLT3) were present in nearly all tumor cells at presentation, and again at relapse 11 months later, suggesting that the patient had a single dominant clone containing all of the mutations. These results demonstrate the power of whole genome sequencing to discover novel cancer-associated mutations.

Published
2008
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8. Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Author

Sandy Aronson, Leslie Cope, Michael L. Bittner, Daniel C. Koboldt, Alex E. Lash, W. K. Alfred Yung, Margaret Morgan, Devin Absher, Carl F. Schaefer, Roger E. McLendon, Michael D. Prados, Josh Gould, Ju Han, Stacey Gabriel, Scott R. VandenBerg, Ilana Perna, Troy Shelton, Junyuan Wu, Sacha Scott, Steve Scherer, Michael J. T. O’Kelly, Li Ding, Erin Hickey, Elizabeth J. Thomson, Bahram Parvin, Kim D. Delehaunty, Gi Choi Yoon, Mark D. Robinson, Oliver Bogler, Darrell D. Bigner, Michael R. Reich, Jianhua Zhang, Robert S. Fulton, Allan H. Friedman, Tammi L. Vickery, Amita Aggarwal, Subhashree Madhavan, Liuda Ziaugra, Yuan Qi, Vandita Joshi, Eric Van Name, Jane Wilkinson, W. Ruprecht Wiedemeyer, Xiaoqi Shi, Richard A. Gibbs, Lynda Chin, Jessica Chen, Stefano Monti, Erwin G. Van Meir, John Ngai, Amy Hawkins, Elizabeth Lenkiewicz, Brad Ozenberger, Shannon Dorton, Georgia Ren, John N. Weinstein, Gena M. Mastrogianakis, Asif T. Chinwalla, Scott L. Carter, Nicholas D. Socci, Rachel Abbott, Gavin Sherlock, Lucinda Fulton, Hyun Soo Kim, Fei Pan, Magali Cavatore, Gabriele Alexe, Francis S. Collins, Narayanan Sathiamoorthy, Lakshmi Jakkula, Brian H. Dunford-Shore, Jireh Santibanez, Tom Mikkelsen, Huy V. Nguyen, Levi A. Garraway, Christopher A. Miller, Jinghui Zhang, Ken Chen, Timothy Fennell, Robert Sfeir, James A. Robinson, Alexey Stukalov, Richard K. Wilson, Matthew Meyerson, Daniel J. Weisenberger, Mi Yi Joo, Yevgeniy Antipin, Anna Lapuk, Gerald V. Fontenay, Nicolas Stransky, Adam B. Olshen, Elizabeth Purdom, Josh Korn, Huyen Dinh, Sai Balu, Victoria Wang, James G. Herman, Christie Kovar, Kristian Cibulskis, Tisha Chung, Agnes Viale, Paul T. Spellman, Supriya Gupta, Melissa Parkin, Peter J. Park, Maddy Wiechert, John W. Wallis, Peter W. Laird, Nikolaus Schultz, James D. Brooks, David Nassau, Jun Li, John R. Osborne, Anna D. Barker, Peter Fielding, Boris Reva, Karen Vranizan, D. Neil Hayes, Aleksandar Milosavljevic, Lawrence A. Donehower, Won Kong Sek, Daniela S. Gerhard, Otis Hall, Rameen Beroukhim, Audrey Southwick, George M. Weinstock, Chris Markovic, Roel G.W. Verhaak, David Van Den Berg, Joe W. Gray, Yanru Ren, Ethan Cerami, Yiming Zhu, Amrita Ray, Yonghong Xiao, Kristin G. Ardlie, William L. Gerald, Michael S. Lawrence, Gerald R. Fowler, Mark S. Guyer, Isaac S. Kohane, Kornel E. Schuebel, Mitchel S. Berger, Jeffrey J. Olson, Gary W. Swift, Lora Lewis, Sheri Sanders, Norman L. Lehman, Eric S. Lander, Robert Penny, Liliana Villafania, John G. Conboy, Ari B. Kahn, Henry Marr, Heidi S. Feiler, Lynn Nazareth, David J. Dooling, Katherine A. Hoadley, Alicia Hawes, Marc Ladanyi, Aniko Sabo, Wendy Winckler, Vivian Peng, Barbara A. Weir, Daniel J. Brat, Scott Morris, Carolyn C. Compton, Todd R. Golub, Scott Abbott, Michael D. McLellan, Jiqiang Yao, Shalini N. Jhangiani, Michael D. Topal, Michael C. Wendl, Gad Getz, Jun Yao, Derek Y. Chiang, Larry Feng, Steffen Durinck, David A. Wheeler, Yuzhu Tang, Benjamin Gross, Barry S. Taylor, Kenneth Aldape, Craig Pohl, Rick Meyer, Peter J. Good, Ling Lin, Elaine R. Mardis, Robert C. Onofrio, Jane Peterson, Stephen B. Baylin, Li-Xuan Qin, Andrew Cree, Cameron Brennan, Charles M. Perou, William Courtney, Omar Alvi, Donna M. Muzny, Joseph G. Vockley, Jill P. Mesirov, Yan Shi, Alexei Protopopov, Jim Vaught, Craig H. Mermel, Scott Mahan, Laetitia Borsu, Heather Schmidt, Jennifer Baldwin, Tracie L. Miner, Toby Bloom, David E. Larson, Leander Van Neste, Nicholas J. Wang, Kenneth H. Buetow, Raju Kucherlapati, Anthony San Lucas, Martin L. Ferguson, Terence P. Speed, Venkatraman E. Seshan, Debbie Beasley, Carrie Sougnez, Carrie A. Haipek, Richard M. Myers, Chris Sander, Qing Wang Wei, Jon G. Seidman, Rob Nicol, Manuel L. Gonzalez-Garay, Shin Leong, Shannon T. Brady, and University of Groningen

Subjects
Male, Models, Molecular, DNA Repair, Gene Dosage, NEUROFIBROMATOSIS TYPE-1, MISMATCH REPAIR, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Genes, Tumor Suppressor, DNA Modification Methylases, Proneural Glioblastoma, Aged, 80 and over, Genetics, 0303 health sciences, Neurofibromin 1, Multidisciplinary, Brain Neoplasms, NF1 GENE, Genomics, Middle Aged, TUMORS, ALKYLATING-AGENTS, 3. Good health, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, DNA methylation, Female, DNA mismatch repair, Functional genomics, Signal Transduction, Adult, Adolescent, CELL-LINES, Oncogenomics, Biology, Article, 03 medical and health sciences, PIK3CA GENE, Humans, Epigenetics, Gene, Aged, Retrospective Studies, 030304 developmental biology, HIGH-FREQUENCY, Genome, Human, Tumor Suppressor Proteins, SOMATIC MUTATIONS, Genes, erbB-1, DNA Methylation, Protein Structure, Tertiary, MALIGNANT GLIOMAS, DNA Repair Enzymes, Mutation, Glioblastoma
Abstract

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

Published
2008
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9. Evolutionary and Biomedical Insights from the Rhesus Macaque Genome

Author

Carolin Kosiol, Belinda Giardine, Janet A. Hopkins, Andrew G. Clark, Ryan D. Hernandez, Peng Wang, Peter D. Stenson, Yu-Hui Rogers, Aaron L. Halpern, Andrew D. Kern, Webb Miller, Kymberlie H. Pepin, Melissa J. Hubisz, Kimberly D. Delehaunty, Robert E. Palermo, Matthew W. Hahn, Erica Sodergren, Brian P. Walenz, Scott M. Smith, Sandra L. Lee, Xiang Qin, Yucheng Feng, Ewen F. Kirkness, Vandita Joshi, Xiaoqiu Huang, Amanda F. Svatek, Fan Yang, Young Ho Kim, Laura Clarke, John E. Karro, Courtney Sherell White, Jessica Kolb, David Glenn Smith, Clay Davis, Jian Ma, Shobha Patil, Todd Wylie, Arian F.A. Smit, Shalini N. Jhangiani, Michael G. Katze, Edward V. Ball, Jennifer Godfrey, Heather A. Lawson, Brian J. Raney, Michael Holder, Ross C. Hardison, Christian J. Buhay, Zhangwan Li, Alicia Hawes, Eric J. Vallender, David A. Wheeler, James C. Wallace, Galt P. Barber, Jinchuan Xing, Yufeng Shen, Kayla E. Smith, Marvin Diep Dao, Jeffrey Rogers, Evan E. Eichler, Cynthia Pfannkoch, Jireh Santibanez, Kateryna D. Makova, Kashif Hirani, Robert M. Kuhn, Yanru Ren, David Neil Cooper, David Haussler, Carlos Bustamante, Adam Siepel, Mimi N. Chandrabose, Xiaoming Liu, George M. Weinstock, Teresa Utterback, Jarret Glasscock, Tomas Vinar, R. Alan Harris, Anis Karimpour-Fard, San Juana Ruiz, Lucinda Fulton, Asif T. Chinwalla, Aniko Sabo, Xinwei She, Charles Addo-Quaye, David L. Nelson, Lora Lewis, Hui Ke, Eli Venter, Donna M. Muzny, Alison Marklein, Bruce T. Lahn, Grace Pai, Brian W. Schneider, Shannon Dugan-Rocha, Henry Xing-Zhi Song, Jeremiah D. Degenhardt, Kyudong Han, Huaiyang Jiang, Stephanie M. Moore, Ian Schenck, Dinh Ngoc Ngo, Michael J. Cox, Heidie A. Paul, Ann S. Zwieg, Kim C. Worley, Craig Pohl, Rui Chen, Robert L. Strausberg, Ling-Ling Pu, Donna Karolchik, Jonathan R. Pollack, Geoffrey Okwuonu, Jennifer Hume, Elaine R. Mardis, David N. Messina, W. James Kent, William E. O'Brien, Fan Hsu, Andrew R. Jackson, Huyen Dinh, Hui Wang, LaDeana W. Hillier, Richard A. Gibbs, Alexandra Denby, Wesley C. Warren, Brygg Ullmer, Laura J. Dumas, Yih-shin Liu, Tony Attaway, Richard K. Wilson, Patrick Minx, James M. Sikela, Lan Zhang, Sandra Hines, Steven J. M. Jones, Amit Indap, Ze Cheng, Karin A. Remington, Stephanie Bell, Jungnam Lee, Kelly E. Bernard, Sang-Gook Han, Mariano Rocchi, Judith Hernandez, Betsy Ferguson, Hildegard Kehrer-Sawatzki, Ziad Khan, Aleksandar Milosavljevic, Joanne O. Nelson, Jeffery P. Demuth, Richard Burhans, David A. Parker, Lynne V. Nazareth, Roger E. Bumgarner, Marco A. Marra, Robert Baertsch, Andrew Cree, Paul Havlak, J. Craig Venter, Kay Prüfer, Rasmus Nielsen, Ewan Birney, Miriam K. Konkel, Mark A. Batzer, Arthur M. Lesk, Jacqueline E. Schein, Granger G. Sutton, Yan Ding, Yue Liu, Andy Peng Xiang, Miklós Csürös, Selina Vattathil, John W. Wallis, R. Gerald Fowler, Shiaw-Pyng Yang, Ramatu Ayiesha Gabisi, and Toni T. Garner

Subjects
Male, Biomedical Research, Pan troglodytes, Macaque, Human accelerated regions, Genome, Evolution, Molecular, Species Specificity, Gene Duplication, biology.animal, Animals, Humans, Primate, Gene Rearrangement, Genetics, Whole genome sequencing, Multidisciplinary, biology, Genetic Diseases, Inborn, Genetic Variation, Sequence Analysis, DNA, Gene rearrangement, biology.organism_classification, Macaca mulatta, Rhesus macaque, Homo sapiens, Evolutionary biology, Multigene Family, Mutation, Female
Abstract

The rhesus macaque ( Macaca mulatta ) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

Published
2007
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10. Genome Modeling System: A Knowledge Management Platform for Genomics

Author

Gabriel E. Sanderson, William E. Schroeder, Chris Harris, Gary Stiehr, Lynn K. Carmichael, Benjamin J. Ainscough, Shawn Leonard, Charles Lu, Ian T. Ferguson, James M. Eldred, Nathaniel G. Nutter, Amy Hawkins, Eric M. Clark, Allison A. Regier, Thomas P. Mooney, Todd Wylie, Elaine R. Mardis, Michael D. McLellan, Michael J. Kiwala, Malachi Griffith, Ken Chen, Joshua F. McMichael, Kyung H. Kim, Travis E. Abbott, Robert T. L. Long, Benjamin S. Abbott, Edward A. Belter, Indraniel Das, Richard W. Wohlstadter, Adam F. Dukes, Matthew B. Callaway, Feiyu Du, Vincent Magrini, Jason Walker, Benjamin J. Oberkfell, Nicole Maher, Zachary L. Skidmore, Cyriac Kandoth, Scott M. Smith, Christopher A. Miller, Jasreet Hundal, Xian Fan, David L. Morton, Todd G. Hepler, Brian R. Derickson, Christopher G. Maher, David J. Dooling, Craig Pohl, David E. Larson, James V. Weible, Xiaoqi Shi, Joshua Peck, Matthew R. Weil, Justin T. Lolofie, Adam C. Coffman, Nathan D. Dees, Li Ding, Anthony M. Brummett, Mark M. Burnett, William Schierding, Avinash Ramu, Richard K. Wilson, Obi L. Griffith, and Daniel C. Koboldt

Subjects
Genome evolution, QH301-705.5, Data management, Knowledge Bases, Genomics, Biology, computer.software_genre, Genome, 03 medical and health sciences, Cellular and Molecular Neuroscience, User-Computer Interface, 0302 clinical medicine, Software, Databases, Genetic, Genetics, Leverage (statistics), Humans, Computer Simulation, Biology (General), Molecular Biology, Exome, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Ecology, Models, Genetic, business.industry, Genome, Human, Chromosome Mapping, Sequence Analysis, DNA, Management information systems, Computational Theory and Mathematics, 030220 oncology & carcinogenesis, Modeling and Simulation, Database Management Systems, Data mining, business, computer, Sequence Alignment, Algorithms, Research Article
Abstract

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

Published
2015

11. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

Author

Hoadley, Katherine A., Yau, Christina, Wolf, Denise M., Cherniack, Andrew D., Tamborero, David, Sam, Ng, Leiserson, Max D. M., Niu, Beifang, Mclellan, Michael D., Uzunangelov, Vladislav, Zhang, Jiashan, Kandoth, Cyriac, Akbani, Rehan, Shen, Hui, Omberg, Larsson, Chu, Andy, Margolin, Adam A., Van'T Veer, Laura J., Lopez Bigas, Nuria, Laird, Peter W., Raphael, Benjamin J., Ding, Li, Robertson, A. Gordon, Byers, Lauren A., Mills, Gordon B., Weinstein, John N., Van Waes, Carter, Chen, Zhong, Collisson, Eric A., Benz, Christopher C, Perou, Charles M., Stuart, Joshua M., Rachel, Abbott, Scott, Abbott, Arman Aksoy, B., Kenneth, Aldape, Adrian, Ally, Samirku mar Amin, Dimitris, Anastassiou, Todd Auman, J., Baggerly, Keith A., Miruna, Balasundaram, Saianand, Balu, Baylin, Stephen B., Benz, Stephen C., Berman, Benjamin P., Brady, Bernard, Bhatt, Ami S., Inanc, Birol, Black, Aaron D., Tom, Bodenheimer, Bootwalla, Moiz S., Jay, Bowen, Ryan, Bressler, Bristow, Christopher A., Brooks, Angela N., Bradley, Broom, Elizabeth, Buda, Robert, Burton, Butterfield, Yaron S. N., Daniel, Carlin, Carter, Scott L., Casasent, Tod D., Kyle, Chang, Stephen, Chanock, Lynda, Chin, Dong Yeon Cho, Juok, Cho, Eric, Chuah, Chun, Hye Jung E., Kristian, Cibulskis, Giovanni, Ciriello, James Cle land, Melisssa, Cline, Brian, Craft, Creighton, Chad J., Ludmila, Danilova, Tanja, Davidsen, Caleb, Davis, Dees, Nathan D., Kim, Delehaunty, Demchok, John A., Noreen, Dhalla, Daniel, Dicara, Huyen, Dinh, Dobson, Jason R., Deepti, Dodda, Harshavardhan, Doddapaneni, Lawrence, Donehower, Dooling, David J., Gideon, Dresdner, Jennifer, Drummond, Andrea, Eakin, Mary, Edgerton, Eldred, Jim M., Greg, Eley, Kyle, Ellrott, Cheng, Fan, Suzanne, Fei, Ina, Felau, Scott, Frazer, Freeman, Samuel S., Jessica, Frick, Fronick, Catrina C., Ful ton, Lucinda L., Robert, Fulton, Gabriel, Stacey B., Jianjiong, Gao, Gastier Foster, Julie M., Nils, Gehlenborg, Myra, George, Gad, Getz, Richard, Gibbs, Mary, Goldman, Abel Gonzalez Perez, Benjamin, Gross, Ranabir, Guin, Preethi, Gunaratne, Angela, Hadjipanayis, Hamilton, Mark P., Hamilton, Stanley R., Leng, Han, Han, Yi, Harper, Hollie A., Psalm, Haseley, David, Haussler, Neil Hayes, D., Heiman, David I., Elena, Helman, Carmen, Helsel, Herbrich, Shelley M., Her man, James G., Toshinori, Hinoue, Carrie, Hirst, Martin, Hirst, Holt, Robert A., Hoyle, Alan P., Lisa, Iype, Anders, Jacobsen, Jeffreys, Stuart R., Jensen, Mark A., Jones, Corbin D., Jones, Steven J. M., Zhenlin, Ju, Joonil, Jung, Andre, Kahles, Ari, Kahn, Joelle Kalicki Veizer, Divya, Kalra, Krishna Latha Kanchi, Kane, David W., Hoon, Kim, Jaegil, Kim, Theo, Knijnenburg, Koboldt, Daniel C., Christie, Kovar, Roger, Kramer, Richard, Kreisberg, Raju, Kucherlapati, Marc, Ladanyi, Lander, Eric S., Larson, David E., Lawrence, Michael S., Darlene, Lee, Eunjung, Lee, Semin, Lee, William, Lee, Kjong Van Lehmann, Kalle, Leinonen, Ler aas, Kristen M., Seth, Lerner, Levine, Douglas A., Lora, Lewis, Ley, Timothy J., Haiyan I., Li, Jun, Li, Wei, Li, Han, Liang, Lichtenberg, Tara M., Jake, Lin, Ling, Lin, Pei, Lin, Wen bin Liu, Yingchun, Liu, Yuexin, Liu, Lorenzi, Philip L., Charles, Lu, Yiling, Lu, Luquette, Love lace J., Singer, Ma, Magrini, Vincent J., Mahadeshwar, Harshad S., Mardis, Elaine R., Adam, Margolin, Marra, Marco A., Michael, Mayo, Cynthia, Mcallister, Mcguire, Sean E., Mcmichael, Joshua F., James, Melott, Shaowu, Meng, Matthew, Meyerson, Mieczkowski, Piotr A., Miller, Christopher A., Miller, Martin L., Michael, Miller, Moore, Richard A., Margaret, Morgan, Donna, Morton, Mose, Lisle E., Mungall, Andrew J., Donna, Muzny, Lam, Nguyen, Noble, Michael S., Houtan, Noushmehr, Michelle, O’Laughlin, Ojesina, Akinyemi I., Tai Hsien Ou Yang, Brad, Ozenberger, Angeliki, Pantazi, Michael, Parfenov, Park, Peter J., Parker, Joel S., Evan, Paull, Chandra Sekhar Pedamallu, Todd, Pihl, Craig, Pohl, David, Pot, Alexei, Protopopov, Teresa, Przytycka, Amie Raden baugh, Ramirez, Nilsa C., Ricardo, Ramirez, Gunnar Ra, ̈ tsch, Jeffrey, Reid, Xiao jia Ren, Boris, Reva, Reynolds, Sheila M., Rhie, Suhn K., Jeffrey, Roach, Hector, Rovira, Michael, Ryan, Gordon, Saksena, Sofie, Salama, Chris, Sander, Netty, Santoso, Schein, Jacqueline E., Heather, Schmidt, Nikolaus, Schultz, Schumacher, Steven E., Jonathan, Seidman, Yasin, Senbabaoglu, Sahil, Seth, Saman tha Sharpe, Ronglai, Shen, Margi, Sheth, Yan, Shi, Ilya, Shmulevich, Silva, Grace O., Simons, Janae V., Rileen, Sinha, Payal, Sipahimalani, Smith, Scott M., Sofia, Heidi J., Artem, Sokolov, Soloway, Mathew G., Xingzhi, Song, Carrie Soug nez, Paul, Spellman, Louis, Staudt, Chip, Stewart, Petar, Stojanov, Xiaoping, Su, Onur Sumer, S., Yichao, Sun, Teresa, Swatloski, Barbara, Tabak, Angela, Tam, Donghui, Tan, Jiabin, Tang, Roy, Tarnuzzer, Taylor, Barry S., Nina, Thiessen, Ves teinn Thorsson, Timothy Triche, J. r., Van Den Berg, David J., Vandin, Fabio, Varhol, Richard J., Vaske, Charles J., Umadevi, Veluvolu, Roeland, Verhaak, Doug, Voet, Jason, Walker, Wallis, John W., Peter, Waltman, Yunhu, Wan, Min, Wang, Wenyi, Wang, Zhining, Wang, Scot, Waring, Nils, Weinhold, Weisenberger, Daniel J., Wendl, Michael C., David, Wheeler, Wilkerson, Matthew D., Wilson, Richard K., Lisa, Wise, Andrew, Wong, Chang Jiun Wu, Chia Chin Wu, Hsin Ta Wu, Junyuan, Wu, Todd, Wylie, Liu, Xi, Ruibin, Xi, Zheng, Xia, Andrew W., Xu, Yang, Da, Liming, Yang, Lixing, Yang, Yang, Yang, Jun, Yao, Rong, Yao, Kai, Ye, Ko suke Yoshihara, Yuan, Yuan, Yung, Alfred K., Travis, Zack, Dong, Zeng, Jean Claude Zenklusen, Hailei, Zhang, Jianhua, Zhang, Nianxiang, Zhang, Qunyuan, Zhang, Wei, Zhang, Wei, Zhao, Siyuan, Zheng, Jing, Zhu, Erik, Zmuda, and Lihua, Zou

Subjects
Genetics and Molecular Biology (all), Cluster Analysis, Humans, Neoplasms, Transcriptome, Biochemistry, Genetics and Molecular Biology (all), Extramural, Biochemistry, Genetics and Molecular Biology(all), Cancer, Computational biology, Disease, Biology, medicine.disease, Bioinformatics, Biochemistry, General Biochemistry, Genetics and Molecular Biology, Article, 3. Good health, Molecular classification, TP63, CLUSTERS (ANÁLISE), medicine, Head and neck, Gene
Abstract

Summary Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.

Published
2014
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12. The Cancer Genome Atlas Pan-Cancer analysis project

Author

Qunyuan Zhang, B. Arman Aksoy, Fabio Vandin, Eric A. Collisson, Larsson Omberg, S. Onur Sumer, John A. Demchok, Sven Nelander, Vladislav Uzunangelov, Michael C. Wendl, Roger Kramer, John W. Wallis, Brian Craft, Angeliki Pantazi, Leng Han, W. K. Alfred Yung, Brad Ozenberger, Philip L. Lorenzi, James G. Herman, Andy Chu, Sahil Seth, Richard A. Gibbs, Angela Hadjipanayis, Hector Rovira, Peter W. Laird, Inanc Birol, Richard K. Wilson, James Cleland, Peter J. Park, Jiashan Zhang, Payal Sipahimalani, Stanley R. Hamilton, Liming Yang, Seth Lerner, Amie Radenbaugh, Barry S. Taylor, Carrie Hirst, David Tamborero, Stephen B. Baylin, Gad Getz, Tanja Davidsen, Miruna Balasundaram, Cheng Fan, Yuan Yuan, Kristian Cibulskis, Yan Shi, Angela Tam, Divya Kalra, Chris Sander, Scott Abbott, Catrina Fronick, Margi Sheth, Chip Stewart, Angela N. Brooks, Noreen Dhalla, Lam Nguyen, Hui Shen, Travis I. Zack, Andrew J. Mungall, Artem Sokolov, Douglas A. Levine, Carrie Sougnez, Paul T. Spellman, Greg Eley, Deepti Dodda, Wenbin Liu, Michael B. Ryan, Liu Xi, Aaron D. Black, Rong Yao, Saianand Balu, Benjamin P. Berman, Raju Kucherlapati, James M. Melott, Xingzhi Song, Boris Reva, Huyen Dinh, David A. Pot, Michael D. McLellan, Kjong-Van Lehmann, Wenyi Wang, Petar Stojanov, Bradley McIntosh Broom, Timothy J. Ley, Da Yang, Mary Elizabeth Edgerton, Houtan Noushmehr, Mathew G. Soloway, Nina Thiessen, Zhenlin Ju, Mark D.M. Leiserson, Michael Parfenov, Laura van 't Veer, Scott L. Carter, Ludmila Danilova, Adrian Ally, Hailei Zhang, Ina Felau, Carmen Helsel, Kenneth Aldape, Teresia Kling, Charles Lu, Psalm Haseley, A. Gordon Robertson, Andrew Wei Xu, Jessica Frick, Benjamin Gross, Louis M. Staudt, Craig Pohl, Dimitris Anastassiou, Netty Santoso, Donna Muzny, Chad J. Creighton, Donghui Tan, Ryan Bressler, Andrew J. Wong, Barbara Tabak, Yasin Senbabaoglu, Daniel C. Koboldt, Darlene Lee, Doug Voet, Joonil Jung, Hollie A. Harper, Jianhua Zhang, Kyle Chang, Wei Zhao, Marc Ladanyi, Lisa Iype, Ricardo Ramirez, Ami S. Bhatt, Lisle E. Mose, Singer Ma, Abel Gonzalez-Perez, Jonathan G. Seidman, Kosuke Yoshihara, Denise M. Wolf, Corbin D. Jones, Patrik Johansson, Siyuan Zheng, André Kahles, Stacey Gabriel, John N. Weinstein, Han Liang, Samantha Sharpe, Steven E. Schumacher, Matthew Meyerson, D. Neil Hayes, David Haussler, Krishna L. Kanchi, Julie M. Gastier-Foster, Umadevi Veluvolu, Ari B. Kahn, Brady Bernard, Tod D. Casasent, Christopher A. Bristow, Akinyemi I. Ojesina, Sam Ng, Charles M. Perou, Moiz S. Bootwalla, Cyriac Kandoth, Lixing Yang, Joel S. Parker, Alan P. Hoyle, Timothy J. Triche, Dong Zeng, Sean E. McGuire, Christie Kovar, Kim D. Delehaunty, Juok Cho, Alexei Protopopov, Shaowu Meng, Ling Lin, Heather Schmidt, Nils Gehlenborg, Yuexin Liu, Elaine R. Mardis, Martin L. Miller, Jake Lin, Jason Walker, Lisa Wise, Suzanne S. Fei, Jacqueline E. Schein, Semin Lee, Christina Yau, Melisssa Cline, Tara M. Lichtenberg, David I. Heiman, Scot Waring, Richard A. Moore, Margaret B. Morgan, Robert S. Fulton, David E. Larson, Xiaoping Su, Kalle Leinonen, Samirkumar B. Amin, Joshua M. Stuart, J. Todd Auman, Rebecka Jörnsten, Rileen Sinha, Andrew D. Cherniack, Caleb F. Davis, Stephen J. Chanock, Nathan D. Dees, Adam Margolin, Haiyan I. Li, Yaron S.N. Butterfield, Daniel E. Carlin, Tai Hsien Ou Yang, Rameen Beroukhim, Vincent Magrini, Mark P. Hamilton, Grace O. Silva, Nils Weinhold, Harshad S. Mahadeshwar, Michael S. Lawrence, Eric Chuah, Jun Li, Wei Li, Robert A. Burton, Teresa M. Przytycka, Katherine A. Hoadley, Keith A. Baggerly, Sheila M. Reynolds, Daniel DiCara, Tom Bodenheimer, Charles J. Vaske, James M. Eldred, Richard Varhol, Mark A. Jensen, David W. Kane, Xiaojia Ren, Christopher A. Miller, Elizabeth Buda, Li Ding, Michael Mayo, Hsin-Ta Wu, Joelle Kalicki-Veizer, Shelley M. Herbrich, Eunjung Lee, Yingchun Liu, Joshua F. McMichael, Jennifer Drummond, Teresa Swatloski, Harshavardhan Doddapaneni, William Lee, Daniel J. Weisenberger, David A. Wheeler, Chia Chin Wu, Richard Kreisberg, Roeland Verhaak, Elena Helman, Piotr A. Mieczkowski, Mary Goldman, Ilya Shmulevich, Nikolaus Schultz, Min Wang, Lovelace J. Luquette, Marco A. Marra, Todd Pihl, Roy Tarnuzzer, Ronglai Shen, Donna Morton, Yichao Sun, Lawrence A. Donehower, Jun Yao, Theo A. Knijnenburg, Benjamin J. Raphael, Lora Lewis, Peter Waltman, Andrea Eakin, Martin Hirst, Jaegil Kim, Lihua Zou, Ranabir Guin, Yi Han, Scott M. Smith, Hoon Kim, Kristen M. Leraas, Heidi J. Sofia, Erik Zmuda, Matthew D. Wilkerson, Michelle O'Laughlin, Jianjiong Gao, Jeffrey G. Reid, Jing Zhu, Toshinori Hinoue, Gunnar Rätsch, Hye Jung E. Chun, Anders Jacobsen, Stephen C. Benz, Kenna R. Mills Shaw, Gordon B. Mills, Zhining Wang, Cynthia McAllister, Michael S. Noble, Christopher C. Benz, Rehan Akbani, Ruibin Xi, Nianxiang Zhang, Jay Bowen, Wei Zhang, Chandra Sekhar Pedamallu, Eric S. Lander, Yunhu Wan, David J. Dooling, Dong Yeon Cho, Preethi Gunaratne, Todd Wylie, Pei Lin, Chang-Jiun Wu, Jeffrey Roach, Scott Frazer, Samuel S. Freeman, Rachel Abbott, Zheng Xia, Lucinda Fulton, Kyle Ellrott, Nuria Lopez-Bigas, Yang Yang, Michael Miller, Nilsa C. Ramirez, Evan O. Paull, Janae V. Simons, Junyuan Wu, Lynda Chin, Gordon Saksena, Jiabin Tang, Vesteinn Thorsson, Robert A. Holt, Suhn K. Rhie, Steven J.M. Jones, Stuart R. Jeffreys, Giovanni Ciriello, Sofie R. Salama, Gideon Dresdner, Yiling Lu, Massachusetts Institute of Technology. Department of Biology, Lander, Eric S., and Park, Peter J.

Subjects
Genetics, medicine.medical_specialty, Genome, Gene Expression Profiling, Genomics, Computational biology, Biology, Humans, Neoplasms, Article, Analysis Project, Gene expression profiling, GENÉTICA MOLECULAR, Cancer genome, Genomic Profile, medicine, Medical genetics, Epigenetics
Abstract

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile., National Cancer Institute (U.S.), National Human Genome Research Institute (U.S.)

Published
2013

13. Evaluation of 16S rDNA-based community profiling for human microbiome research

Author

Michael Feldgarden, Shibu Yooseph, Divya Kalra, Theresa A. Hepburn, Navjeet Singh, Richard A. Gibbs, Shawn Leonard, Richard K. Wilson, Elizabeth L. Appelbaum, Niall J. Lennon, Hongyu Gao, Kathie A. Mihindukulasuriya, Bonnie P. Youmans, Lynn K. Carmichael, Yue Shang, Xiang Qin, Ashlee M. Earl, George M. Weinstock, Candace N. Farmer, Scott Anderson, Yu Hui A. Rogers, Erica Sodergren, Otis Hall, Georgia Giannoukos, Joseph F. Petrosino, Brian J. Haas, Todd Z. DeSantis, Kim C. Worley, Michelle O'Laughlin, Craig Pohl, Dawn Ciulla, Matthew C. Ross, Bruce W. Birren, Patrick D. Schloss, Rachel L. Erlich, Lucinda Fulton, Yanjiao Zhou, David J. Dooling, Toby Bloom, Donna M. Muzny, Katarzyna Wilczek-Boney, Leigh Aird, Sarah K. Highlander, Kelvin Li, Elaine R. Mardis, Dirk Gevers, Doyle V. Ward, Vincent Magrini, Keenan Ross, Vandita Joshi, Tulin Ayvaz, John Gill, Christie Kovar, Diana Tabbaa, Susanna Hamilton, Karen E. Nelson, Lora Lewis, Robert S. Fulton, Lisa Hemphill, Jonathan Crabtree, Cesar Arze, Jennifer R. Wortman, Barbara A. Methé, Cristyn Kells, Edward A. Belter, Laura Courtney, and Monika Bihan

Subjects
Ecological Metrics, lcsh:Medicine, Computational biology, Biology, Biochemistry, Microbiology, Microbial Ecology, 03 medical and health sciences, DNA amplification, RNA, Ribosomal, 16S, Humans, Profiling (information science), Genome Sequencing, lcsh:Science, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Bacteria, Ecology, 030306 microbiology, Bacterial Taxonomy, lcsh:R, Human microbiome, Computational Biology, Bayes Theorem, Species Diversity, Bacteriology, DNA, Genomics, Biodiversity, 16S ribosomal RNA, 3. Good health, Nucleic acids, Earth Microbiome Project, Metagenome, lcsh:Q, Metagenomics, Species Richness, Research Article, Human Microbiome Project
Abstract

The Human Microbiome Project will establish a reference data set for analysis of the microbiome of healthy adults by surveying multiple body sites from 300 people and generating data from over 12,000 samples. To characterize these samples, the participating sequencing centers evaluated and adopted 16S rDNA community profiling protocols for ABI 3730 and 454 FLX Titanium sequencing. In the course of establishing protocols, we examined the performance and error characteristics of each technology, and the relationship of sequence error to the utility of 16S rDNA regions for classification- and OTU-based analysis of community structure. The data production protocols used for this work are those used by the participating centers to produce 16S rDNA sequence for the Human Microbiome Project. Thus, these results can be informative for interpreting the large body of clinical 16S rDNA data produced for this project.

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. Comparative and demographic analysis of orang-utan genomes

Author

Matthew W. Hahn, Andreas Heger, Carolin Kosiol, Lisa Cook, Arindam RoyChoudhury, Arcadi Navarro, Catrina Fronick, Lin Chen, Devin P. Locke, Oliver A. Ryder, Olga Fernando, Tomas Vinar, Adam Siepel, Jian Ma, Jeremiah D. Degenhardt, Giuliano Della Valle, Brona Brejova, Oronzo Capozzi, Christie Kovar, Nicoletta Archidiacono, Lucinda Fulton, Jerilyn A. Walker, Albert J. Vilella, Domènec Farré, Julien Y. Dutheil, Xose S. Puente, Mikkel H. Schierup, Carlos Bustamante, George M. Weinstock, Lynne V. Nazareth, Can Alkan, Robert S. Fulton, Brian J. Raney, Mark A. Batzer, Tina Graves, Stephen M. J. Searle, Miriam K. Konkel, Yuko Yoshinaga, Donna M. Muzny, Mariano Rocchi, Carlos López-Otín, Bernard B. Suh, Thomas Mailund, Gonzalo R. Ordóñez, Robert Hubley, Claudio Casola, Huyen Dinh, Rui Faria, Joanne O. Nelson, Tomas Marques-Bonet, Vincent Magrini, Chris Markovic, Makedonka Mitreva, Zhengyuan Wang, Elaine R. Mardis, Arian F.A. Smit, Asger Hobolth, Javier Herrero, David Haussler, Pieter J. de Jong, Kim C. Worley, Heather Schmidt, Ryan N. Gutenkunst, Webb Miller, Yuan Chen, Richard Burhans, Gerton Lunter, Simon D. M. White, André L. Martins, Richard A. Gibbs, Wesley C. Warren, Richard K. Wilson, Patrick Minx, Elodie Gazave, Xin Ma, Daniel R. Schrider, Chris P. Ponting, Roberta Roberto, Shiaw-Pyng Yang, Víctor Quesada, Stefania Purgato, Evan E. Eichler, Andy Cree, Brygg Ullmer, Jeffrey Rogers, Fleur Darré, Robert S. Harris, Vikas Taliwal, Jeffrey M. Kidd, Craig Pohl, Aakrosh Ratan, Paul Flicek, Meritxell Oliva, Kim D. Delehaunty, LaDeana W. Hillier, Jennifer Hume, Stephen Meader, Ze Cheng, Asif T. Chinwalla, Heather A. Lawson, Gerald R. Fowler, National Human Genome Research Institute (US), National Institutes of Health (US), National Science Foundation (US), David and Lucile Packard Foundation, Cornell University, Medical Research Council (UK), European Commission, Ministerio de Ciencia e Innovación (España), Fundación Botín, Instituto Nacional de Bioinformática (España), Fundação para a Ciência e a Tecnologia (Portugal), Locke, Devin P, Hillier, Ladeana W., Warren, Wesley C., Worley, Kim C., Nazareth, Lynne V., Muzny, Donna M., Yang, Shiaw-Pyng, Wang, Zhengyuan, Chinwalla, Asif T., Minx, Pat, Mitreva, Makedonka, Cook, Lisa, Delehaunty, Kim D., Fronick, Catrina, Schmidt, Heather, Fulton, Lucinda A., Fulton, Robert S., Nelson, Joanne O., Magrini, Vincent, Pohl, Craig, Graves, Tina A., Markovic, Chri, Cree, Andy, Dinh, Huyen H., Hume, Jennifer, Kovar, Christie L., Fowler, Gerald R., Lunter, Gerton, Meader, Stephen, Heger, Andrea, Ponting, Chris P., Marques-Bonet, Toma, Alkan, Can, Chen, Lin, Cheng, Ze, Kidd, Jeffrey M., Eichler, Evan E., White, Simon, Searle, Stephen, Vilella, Albert J., Chen, Yuan, Flicek, Paul, Ma, Jian, Raney, Brian, Suh, Bernard, Burhans, Richard, Herrero, Javier, Haussler, David, Faria, Rui, Fernando, Olga, Darré, Fleur, Farré, Doménec, Gazave, Elodie, Oliva, Meritxell, Navarro, Arcadi, Roberto, Roberta, Capozzi, Oronzo, Archidiacono, Nicoletta, Della Valle, Giuliano, Purgato, Stefania, Rocchi, Mariano, Konkel, Miriam K., Walker, Jerilyn A., Ullmer, Brygg, Batzer, Mark A., Smit, Arian F. A., Hubley, Robert, Casola, Claudio, Schrider, Daniel R., Hahn, Matthew W., Quesada, Victor, Puente, Xose S., Ordõez, Gonzalo R., Ĺpez-Otín, Carlo, Vinar, Toma, Brejova, Brona, Ratan, Aakrosh, Harris, Robert S., Miller, Webb, Kosiol, Carolin, Lawson, Heather A., Taliwal, Vika, Martins, André L., Siepel, Adam, Roychoudhury, Arindam, Ma, Xin, Degenhardt, Jeremiah, Bustamante, Carlos D., Gutenkunst, Ryan N., Mailund, Thoma, Dutheil, Julien Y., Hobolth, Asger, Schierup, Mikkel H., Ryder, Oliver A., Yoshinaga, Yuko, De Jong, Pieter J., Weinstock, George M., Rogers, Jeffrey, Mardis, Elaine R., Gibbs, Richard A., and Wilson, Richard K.

Subjects
Male, Pongo abelii, Genetic Speciation, Population, Population Dynamics, Centromere, Zoology, Biology, Southeast asian, Chromosome, Genome, Chromosomes, Article, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Pongo pygmaeus, Effective population size, Cerebrosides, Species Specificity, Animals, Humans, education, Phylogeny, 030304 developmental biology, Comparative genomics, Cerebroside, Gene Rearrangement, Population Density, 0303 health sciences, education.field_of_study, Population Dynamic, Multidisciplinary, Animal, Medicine (all), Genetic Variation, Gene rearrangement, 3. Good health, Genetics, Population, Evolutionary biology, Female, Pongo pygmaeu, 030217 neurology & neurosurgery, Human
Abstract

5 páginas, 5 figuras, 2 tablas.-- This paper is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike Licence, and is freely available to all readers atwww.nature.com/nature.-- et al., ‘Orang-utan’ is derived from a Malay term meaning ‘man of the forest’ and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal1, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (Ne) expanded exponentially relative to the ancestral Ne after the split, while Bornean Ne declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts., The orang-utan genome project was funded by the National Human Genome Research Institute (NHGRI), including grantsU54HG003079 (R.K.W.) and U54 HG003273 (R.A.G), with further support from National Institutes of Health R01 GM59290 (M.A.B.), PO1 AG022064 (M.A.B.), HG002385 (E.E.E.) and HG002238 (W.M.), National Science Foundation DBI-0644111 (A.S. and B.B.), David and Lucile Packard Foundation(A.S., V.T. and T.V.),CornellUniversity Provost’s Fellowship (A.L.M.), UK Medical Research Council (C.P.P., G.L., S.M. and A.H.), Marie Curie Fellowship (T.M.-B.), Ministerio de Ciencia e Innovación-Spain (MCI-Spain) and Fundación M. Botín (V.Q., X.S.P., G.R.O. and C.L.-O.), MCI-Spain BFU2006-15413-C02-01 and BFU2009-13409-C02-02 (A.N.), Spanish National Institute for Bioinformatics (INAB) and Fundação para a Ciência e a Tecnologia (Portugal), SFRH/BPD/26384/2006(R.F.) and SFRH/BD/15856/2005 (O.F.), PRIN and CEGBA (M.R., N.A. and G.D.V.), and the Commission of the European Communities IRG-224885 (T.V.), IRG-231025 (B.B.).

Published
2011
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16. A catalog of reference genomes from the human microbiome

Author

Dirk Gevers, Doyle V. Ward, Sean M. Sykes, Justin Johnson, Michael Fitzgerald, Jessica B. Hostetler, Sarah Young, Dianhui Zhu, Jason R. Miller, Chinnappa D. Kodira, Aaron M. Berlin, Erica Sodergren, Michael G. Surette, Matthew D. Pearson, Asif T. Chinwalla, Ashlee M. Earl, Michael Feldgarden, Kim C. Worley, Christian J. Buhay, Lisa Hemphill, Manolito Torralba, Xiang Qin, Jonathan H. Badger, Clint Howarth, Marcus Gillis, Candace N. Farmer, Karen E. Nelson, Bruce W. Birren, Richard A. Gibbs, Sandra W. Clifton, Mike Holder, Aye Wollam, Carsten Russ, Wesley C. Warren, Brian J. Haas, Michelle G. Giglio, Qiang Xu, Richard K. Wilson, Patrick Minx, Scott Durkin, Chad Nusbaum, Craig Pohl, Robert S. Fulton, Steve Ferriera, Chandri N. Yandava, Sharvari Gujja, Qiandong Zeng, Ramana Madupu, Victor Markowitz, Joshua Orvis, Andrew Cree, Chad Tomlinson, Donna M. Muzny, Vandita Joshi, Amrita Pati, Christie Kovar, Theresa A. Hepburn, Nikos C. Kyrpides, Kymberlie H. Pepin, Douglas B. Rusch, Granger G. Sutton, Amr Abouellleil, Konstantinos Liolios, Sarah K. Highlander, Yan Ding, Jamison McCorrison, George M. Weinstock, Kris A. Wetterstrand, Emma Allen-Vercoe, Teena Mehta, Lucinda Fulton, Katarzyna Wilczek-Boney, Makedonka Mitreva, Lei Chen, Joseph F. Petrosino, Heather Huot Creasy, Shannon Dugan, Lan Zhang, Owen White, Robert L. Strausberg, Jennifer R. Wortman, Jonathan Crabtree, and Barbara A. Methé

Subjects
Sequence analysis, Respiratory System, Urogenital System, Biology, Genome, Article, Bacterial Proteins, Phylogenetics, Genome, Archaeal, Databases, Genetic, Humans, Microbiome, Gene, Phylogeny, Skin, Genetics, Mouth, Multidisciplinary, Bacteria, Human microbiome, Computational Biology, Genetic Variation, Biodiversity, Sequence Analysis, DNA, Gastrointestinal Tract, Metagenomics, Genes, Bacterial, Metagenome, Peptides, Genome, Bacterial, Reference genome
Abstract

The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97%) were unique. In addition, this set of microbial genomes allows for approximately 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented.

Published
2010

17. Recurring mutations found by sequencing an acute myeloid leukemia genome

Author

Li Ding, Anthony M. Brummett, Peter Westervelt, Jason Walker, Ken Chen, Jonathan K. Schindler, Mark A. Watson, Jerry S. Reed, Timothy J. Ley, Lynn K. Carmichael, Kim D. Delehaunty, Craig Pohl, Daniel C. Link, John W. Wallis, Michael D. McLellan, Jacqueline E. Payton, Richard K. Wilson, Rhonda E. Ries, Heather Schmidt, Tammi L. Vickery, Sean McGrath, Jolynda V. Ivy, Chris Harris, David E. Larson, Sharon Heath, Eric M. Clark, Devin P. Locke, Rick Meyer, Joelle Kalicki, Vincent Magrini, Scott M. Smith, Jody S. Robinson, Yuzhu Tang, Todd Wylie, Rakesh Nagarajan, Carrie A. Haipek, Adam F. Dukes, Madeline E. Wiechert, Gabriel E. Sanderson, Feiyu Du, Michael H. Tomasson, David J. Dooling, Glendoria Elliott, William D. Shannon, Rachel Abbott, Lucinda Fulton, John F. DiPersio, Joshua F. McMichael, Jack Baty, Xiaoqi Shi, Joshua Peck, Timothy A. Graubert, Ling Lin, Elaine R. Mardis, Robert S. Fulton, James M. Eldred, Matthew J. Walter, and Daniel C. Koboldt

Subjects
Adult, Male, DNA Mutational Analysis, Enasidenib, Biology, medicine.disease_cause, Genome, Article, Gene Frequency, medicine, Humans, Point Mutation, Gene, Allele frequency, Genetics, Mutation, Genome, Human, Point mutation, Myeloid leukemia, General Medicine, Sequence Analysis, DNA, Middle Aged, Isocitrate Dehydrogenase, Leukemia, Myeloid, Acute, Human genome, Female, Nucleophosmin
Abstract

The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known.We used massively parallel DNA sequencing to obtain a very high level of coverage (approximately 98%) of a primary, cytogenetically normal, de novo genome for AML with minimal maturation (AML-M1) and a matched normal skin genome.We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome. All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample. Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested. Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 gene, was present in 15 of 187 additional AML genomes tested and was strongly associated with normal cytogenetic status; it was present in 13 of 80 cytogenetically normal samples (16%). The other was a nongenic mutation in a genomic region with regulatory potential and conservation in higher mammals; we detected it in one additional AML tumor. The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis.By comparing the sequences of tumor and skin genomes of a patient with AML-M1, we have identified recurring mutations that may be relevant for pathogenesis.

Published
2009

18. Somatic mutations affect key pathways in lung adenocarcinoma

Author

Aldi T. Kraja, Brian H. Dunford-Shore, Tittu Mathew, Otis Hall, Barbara A. Weir, Timothy Fennell, William Pao, Jack A. Roth, Alicia Hawes, Heidi Greulich, Steven E. Scherer, Xiaoqi Shi, Giovanni Tonon, Manuel L. Gonzalez-Garay, Yuzhu Tang, Mark B. Orringer, Qunyuan Zhang, Bruce E. Johnson, Li Ding, David G. Beer, Amit Dutt, Margaret R. Spitz, Carrie A. Haipek, Michael A. Province, Yiming Zhu, Liuda Ziaugra, Lucian R. Chirieac, Ken Chen, Rachel Abbott, William D. Travis, George M. Weinstock, Harold E. Varmus, Lucinda Fulton, Daniel C. Koboldt, Kristian Cibulskis, Carrie Sougnez, Christopher S. Sawyer, Richard A. Gibbs, Bradley A. Ozenberger, Thomas J. Giordano, Heather Schmidt, Ling Lin, Jennifer Baldwin, Elaine R. Mardis, Rick Meyer, Tracie L. Miner, David E. Larson, Ignacio I. Wistuba, Jiqiang Yao, Margaret Morgan, Andrew C. Chang, Akihiko Yoshizawa, Shalini N. Jhangiani, Xiaojun Zhao, David A. Wheeler, Stephen R. Broderick, Jody S. Robinson, Kerstin Clerc, Eric S. Lander, Richard K. Wilson, Ginger A. Fewell, Hua Shen, David J. Dooling, Robert S. Fulton, Aleksandar Milosavljevic, John R. Osborne, Gad Getz, Donna M. Muzny, Yanru Ren, Wendy Winckler, Roman K. Thomas, Mark A. Watson, Peter J. Good, Sacha N. Sander, Megan Hanna, Michael D. McLellan, Ginger A. Metcalf, Brian Ng, Michael C. Wendl, Lora Lewis, Seth D. Crosby, Michael C. Zody, Matthew Meyerson, Robert C. Onofrio, Michael S. Lawrence, Marc Ladanyi, Aniko Sabo, Craig Pohl, Stacey Gabriel, Tammi L. Vickery, Ding, L, Getz, G, Wheeler, Da, Mardis, Ea, Mclellan, Md, Cibulskis, K, Sougnez, C, Greulich, H, Muzny, Dm, Morgan, Mb, Fulton, L, Fulton, R, Zhang, Q, Wendl, Mc, Lawrence, M, Larson, De, Chen, K, Dooling, Dj, Sabo, A, Hawes, Ac, Shen, H, Jhangiani, Sh, Lewis, Lr, Hall, O, Zhu, Y, Mathew, T, Ren, Y, Yao, J, Scherer, Se, Clerc, K, Metcalf, Ga, Ng, B, Milosavljevic, A, Gonzalez-Garay, Ml, Osborne, Jr, Meyer, R, Shi, X, Tang, Y, Koboldt, Dc, Lin, L, Abbott, R, Miner, Tl, Pohl, C, Fewell, G, Haipek, C, Schmidt, H, Dunford-Shore, Bh, Kraja, A, Crosby, Sd, Sawyer, C, Vickery, T, Sander, S, Robinson, J, Winckler, W, Baldwin, J, Chirieac, Lr, Dutt, A, Fennell, T, Hanna, M, Johnson, Be, Onofrio, Rc, Thomas, Rk, Tonon, G, Weir, Ba, Zhao, X, Ziaugra, L, Zody, Mc, Giordano, T, Orringer, Mb, Roth, Ja, Spitz, Mr, Wistuba, Ii, Ozenberger, B, Good, Pj, Chang, Ac, Beer, Dg, Watson, Ma, Ladanyi, M, Broderick, S, Yoshizawa, A, Travis, Wd, Pao, W, Province, Ma, Weinstock, Gm, Varmus, He, Gabriel, Sb, Lander, E, Gibbs, Ra, Meyerson, M, and Wilson, Rk.

Subjects
Male, Genetics, Mutation, Lung Neoplasms, Multidisciplinary, Tumor suppressor gene, DNA repair, Gene Dosage, Adenocarcinoma, Bronchiolo-Alveolar, Biology, medicine.disease, medicine.disease_cause, Article, Gene Expression Regulation, Neoplastic, Germline mutation, Proto-Oncogenes, medicine, Humans, Adenocarcinoma, Female, Genes, Tumor Suppressor, Carcinogenesis, Lung cancer, Gene
Abstract

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.

Published
2008

19. Design and implementation of a generalized laboratory data model

Author

LaDeana W. Hillier, David J. Dooling, Mike Nhan, Shin Leong, Kevin Crouse, Lynn K. Carmichael, Michael C. Wendl, Todd G. Hepler, Benjamin J. Oberkfell, Craig Pohl, Scott M. Smith, Elaine R. Mardis, Asif T. Chinwalla, and Richard K. Wilson

Subjects
Databases, Factual, Computer science, 030303 biophysics, Information Storage and Retrieval, lcsh:Computer applications to medicine. Medical informatics, computer.software_genre, Biochemistry, User-Computer Interface, 03 medical and health sciences, Structural Biology, Schema (psychology), Information system, lcsh:QH301-705.5, Molecular Biology, 030304 developmental biology, 0303 health sciences, Application programming interface, Database, business.industry, Methodology Article, Applied Mathematics, Computational Biology, Models, Theoretical, Computer Science Applications, Management information systems, Workflow, lcsh:Biology (General), Data model, lcsh:R858-859.7, Database Management Systems, Laboratories, Software engineering, business, computer, Workflow management system
Abstract

Background Investigators in the biological sciences continue to exploit laboratory automation methods and have dramatically increased the rates at which they can generate data. In many environments, the methods themselves also evolve in a rapid and fluid manner. These observations point to the importance of robust information management systems in the modern laboratory. Designing and implementing such systems is non-trivial and it appears that in many cases a database project ultimately proves unserviceable. Results We describe a general modeling framework for laboratory data and its implementation as an information management system. The model utilizes several abstraction techniques, focusing especially on the concepts of inheritance and meta-data. Traditional approaches commingle event-oriented data with regular entity data in ad hoc ways. Instead, we define distinct regular entity and event schemas, but fully integrate these via a standardized interface. The design allows straightforward definition of a "processing pipeline" as a sequence of events, obviating the need for separate workflow management systems. A layer above the event-oriented schema integrates events into a workflow by defining "processing directives", which act as automated project managers of items in the system. Directives can be added or modified in an almost trivial fashion, i.e., without the need for schema modification or re-certification of applications. Association between regular entities and events is managed via simple "many-to-many" relationships. We describe the programming interface, as well as techniques for handling input/output, process control, and state transitions. Conclusion The implementation described here has served as the Washington University Genome Sequencing Center's primary information system for several years. It handles all transactions underlying a throughput rate of about 9 million sequencing reactions of various kinds per month and has handily weathered a number of major pipeline reconfigurations. The basic data model can be readily adapted to other high-volume processing environments.

Published
2007
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20. Initial sequence of the chimpanzee genome and comparison with the human genome

Author

Xose S. Puente, Edward J. Kulbokasl, Tina Graves, Lucinda L. Fulton, Xiaoqiu Huang, Wolfgang Enard, Tracie L. Miner, Peer Bork, Arian F.A. Smit, Mario Ventura, Ge Liu, Eray Tüzün, Jean L. Chang, W. James Kent, Daniel J. Richter, Robert H. Waterston, Maryellen Ruvolo, Sante Gnerre, Toshiyuki Hayakawa, David B. Jaffe, Ines Hellmann, Svante Pääbo, Ajit Varki, Gloria Velasco, Carlos López-Otín, Asif T. Chinwalla, Orna Man, Gustavo Glusman, Catrina Fronick, Katherine S. Pollard, Tarjei S. Mikkelsen, Craig Pohl, Nick Patterson, Scott M. Smith, Kateryna D. Makova, Jonathan Butler, William E. Nash, Mariano Rocchi, Pieter J. de Jong, Ze Cheng, Evan E. Eichler, Hongkai Ji, Mikita Suyama, Tasha K. Altheide, Kerstin Lindblad-Toh, Yoav Gilad, Kay Prüfer, James E. Taylor, Karen E. Hayden, Joanne O. Nelson, Mary Claire King, Evan Mauceli, Michael C. Wendl, Ming K. Lee, David Reich, Richard K. Wilson, Eric S. Lander, Nicoletta Archidiacono, Kimberley D. Delehaunty, Shiaw-Pyng Yang, Kate R. Rosenbloom, LaDeana W. Hillier, Michael C. Zody, John W. Wallis, David Torrents, Stephen F. Schaffner, and Elaine R. Mardis

Subjects
Genome evolution, Time Factors, Pan troglodytes, Biology, ENCODE, Genome, Chimpanzee genome project, Evolution, Molecular, Alu Elements, biology.animal, Animals, Humans, Disease, Alleles, Phylogeny, Whole genome sequencing, Genetics, Recombination, Genetic, Base Composition, Multidisciplinary, Polymorphism, Genetic, Genome, Human, Computational Biology, Genome project, Genomics, Sequence Analysis, DNA, Telomere, Evolutionary biology, Mutagenesis, DNA Transposable Elements, Common chimpanzee, Reference genome
Abstract

Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences that have accumulated since the human and chimpanzee species diverged from our common ancestor, constituting approximately thirty-five million single-nucleotide changes, five million insertion/deletion events, and various chromosomal rearrangements. We use this catalogue to explore the magnitude and regional variation of mutational forces shaping these two genomes, and the strength of positive and negative selection acting on their genes. In particular, we find that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles. We also use the chimpanzee genome as an outgroup to investigate human population genetics and identify signatures of selective sweeps in recent human evolution.

Published
2005

21. Generation and annotation of the DNA sequences of human chromosomes 2 and 4

Author

Xinwei She, Sara Dauphin-Kohlberg, Robert H. Waterston, Patricia Wohldmann, Joelle Kalicki, Ivan Ovcharenko, Shawn Leonard, Scott Kruchowski, Ernest Goyea, William Haakenson, Scott Abbott, Catrina Fronick, Aniko Sabo, Maria Cedroni, Edward A. Belter, Hui Du, Asif T. Chinwalla, Kelly Mead, Michael C. Wendl, Rachel Maupin, Amber Isak, David R. Cox, Tamberlyn Bieri, LaDeana W. Hillier, Lee Trani, Neenu Grewal, Aye Mon Tin-Wollam, Rick Meyer, Lachlan G. Oddy, Lucinda Fulton, Li Ding, Richard M. Myers, Neha Shah, Colin Kremitzki, Tracie L. Miner, Holland Bradshaw-Cordum, Tina Graves, Glendoria Elliott, Matthew T. Hickenbotham, Wesley C. Warren, Mandeep Sekhon, Anu Desai, Jason Carter, Thomas Erb, Webb Miller, Prashant R. Sinha, Richard K. Wilson, Krista Haglund, John Spieth, Craig Pohl, Lisa Cook, John Douglas Mcpherson, Patrick Minx, Susan M. Rock, Ginger A. Fewell, Thomas A. Jones, Michael C. Becker, Yoram Shotland, Chunyan Wang, Jason Waligorski, Kyung Kim, Nicolas Berkowicz, Amy Kozlowicz-Reilly, Johar Ali, Xiaoqiu Huang, Shiaw Pyng Yang, Sean R. Eddy, Mikita Suyama, Francesca D. Ciccarelli, Martin Yoakum, John W. Wallis, Kristine M. Wylie, Maxim Radionenko, Donald Williams, Richard Harkins, Terrence S. Furey, Jacqueline E. Snider, Michael D. McLellan, Andrea Holmes, Shunfang Hou, Johanna Thompson, Andrew Van Brunt, Hui Sun, Teresa Davidson, Rekha Meyer, Feiyu Du, Jennifer Randall-Maher, Chad Tomlinson, Jon R. Armstrong, Robert S. Fulton, William E. Nash, Philip Ozersky, Marc Cotton, Sandra W. Clifton, Elisa Izaurralde, Lauren Caruso, Joanne O. Nelson, James M. Eldred, Sharhonda Swearengen-Shahid, Marco A. Marra, Caryn Wagner-McPherson, Cindy Strong, David Torrents, Phil Latreille, Peer Bork, Elaine R. Mardis, Andrew Levy, Evan E. Eichler, Laura Courtney, Anthony R. Harris, Jeremy Schmutz, Christine Nguyen, Dan Layman, James Taylor, Matt Cordes, Joseph T. Strong, Kimberly D. Delehaunty, Kymberlie H. Pepin, Scott Martinka, Tony Gaige, Charlene Pearman, and John R. Osborne

Subjects
Primates, RNA, Untranslated, Centromere, Molecular Sequence Data, Biology, Euchromatin, Chromosome 16, Chromosome 19, Gene Duplication, Animals, Humans, RNA, Messenger, Conserved Sequence, Genetics, Expressed Sequence Tags, Recombination, Genetic, Base Composition, Multidisciplinary, Polymorphism, Genetic, Base Sequence, Genetic Variation, Proteins, Genomics, Sequence Analysis, DNA, Physical Chromosome Mapping, Chromosome 17 (human), Chromosome 4, Chromosome 3, Chromosomes, Human, Pair 2, CpG Islands, Chromosome 20, Chromosomes, Human, Pair 4, Chromosome 21, Chromosome 22, Pseudogenes
Abstract

Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.

Published
2004

22. Initial sequencing and comparative analysis of the mouse genome

Author

Laura Elnitski, David B. Jaffe, Jia Li, Marina Alexandersson, Michael J. Morgan, Shiaw Pyng Yang, Robert Baertsch, Claire M. Wade, John Tromp, Michael C. Zody, Terrence S. Furey, Emma Overton-Larty, Stephen D. Brown, Scott Schwartz, Diane M. Dunn, J. P. Leger, Kris A. Wetterstrand, David Torrents, Ratna Shownkeen, Brian Schultz, Kim C. Worley, Richard D. Emes, John Mayer, Tom Landers, Beverley Meredith, Carol Scott, R. J. Weber, Sean R. Eddy, David Kulp, Jun Kawai, J Bailey, Fan Hsu, Diana L. Kolbe, Kirsten McLay, Marc Botcherby, Richard Mott, Tracie L. Miner, Jill P. Mesirov, Cristyn Kells, Michael A. Quail, Melanie M. Wall, Alistair G. Rust, Josep F. Abril, Ian F Korf, Peter An, Roderic Guigó, Abel Ureta-Vidal, Evan Mauceli, L. Steven Johnson, Arian F.A. Smit, Arkadiusz Kasprzyk, Michael C. Wendl, Deanna M. Church, Francis S. Collins, Wayne N. Frankel, Pallavi Eswara, Bin Ma, Robert H. Waterston, Stylianos E. Antonarakis, Edward M. Rubin, John Douglas Mcpherson, Andrew Sheridan, Megan McCarthy, Ming Li, Colin N. Dewey, Justin Deri, Rosie Levine, Matthew Jones, Sheila Dodge, Richard R. Copley, Leo Goodstadt, Shan Yang, Donna Maglott, Jamey Wierzbowski, Nick Goldman, Evgeny M. Zdobnov, Simon G. Gregory, C M Clee, Steven Leonard, Elaine R. Mardis, Simon C. Potter, Sarah Sims, Richard A. Gibbs, Mark S. Guyer, Francesca Chiaromonte, Susan Lucas, Mark Diekhans, Steve Searle, Rachel Ainscough, Jane Peterson, Emmanouil T. Dermitzakis, Robert Nicol, Lucy Matthews, Guy Slater, Adam Felsenfeld, Karen Foley, Lucinda Fulton, Tim Hubbard, Richard K. Wilson, Deana W. LaHillier, W. Richard McCombie, Johanna Thompson, Robert David, John Attwood, Anthony P. West, Jane Rogers, Evan Keibler, Lisa Cook, Raju Kucherlapati, Steven Seaman, William E. Nash, Ian J. Jackson, Jonathan Singer, Axin Hua, Tina Graves, Ted Sharpe, Dudley Wyman, Bruce W. Birren, Stuart McLaren, David Willey, A Joy, Douglas Smith, Alexandre Reymond, Paul Flicek, Simon Cawley, Richa Agarwala, Diane Gage, Evanne Trevaskis, Ginger A. Fewell, Michael R. Brent, Tracy C. Ponce, W. James Kent, Timothy Holzer, Eduardo Eyras, Michael J. O’Connor, Webb Miller, Donna M. Muzny, Andrew von Niederhausern, Inna Dubchak, Eitan E. Winter, Catherine Ucla, Arne Stabenau, Michael N. Nhan, Piero Carninci, Michele Clamp, Pavel A. Pevzner, James Meldrim, Tim Cutts, R. D. Campbell, Joy Davies, Wratko Hlavina, Elinor K. Karlsson, David Haussler, John Burton, Peer Bork, Nicole Stange-Thomann, Mikita Suyama, Mark J. Daly, Ewan Birney, Edward J. Kulbokas, Craig Pohl, James C. Mullikin, Chad Nusbaum, Genís Parra, Jade P. Vinson, Yoshihide Hayashizaki, Sante Gnerre, Eric Berry, Daniel G. Brown, Asif T. Chinwalla, Emmanuel Mongin, Robert B. Weiss, Raymond Wheeler, Andrew Kirby, Yasushi Okazaki, Lior Pachter, Ross C. Hardison, Brian Spencer, Carol J. Bult, Joanne O. Nelson, Pankaj K. Agarwal, Darren Grafham, Gustavo Glusman, Thomas A. Jones, Glenn Tesler, Simon Whelan, James Cuff, Robert S. Fulton, K F Barlow, Jörg Schultz, Matthias S. Schwartz, Alex Poliakov, Jonathan Butler, Bruce A. Roe, Angela S. Hinrichs, Alan Coulson, Kate Montgomery, Eric D. Green, Stephan Beck, Val Curwen, Krishna M. Roskin, Robert W. Plumb, Chris P. Ponting, Ralph Santos, Victor Sapojnikov, Nicolas Bray, Kymberlie H. Pepin, Charles W. Sugnet, Olivier Couronne, Ivica Letunic, Sophie Williams, Kimberly D. Delehaunty, Kerstin Lindblad-Toh, Zemin Ning, Karen Oliver, Toby Bloom, Michael Kamal, Nicholas J. Dickens, Eric S. Lander, Christine Lloyd, Donna Karolchik, Adrienne Hunt, Antonarakis, Stylianos, Couronne, Olivier, Dermitzakis, Emmanouil, and Zdobnov, Evgeny

Subjects
RNA, Untranslated, Proteome, Untranslated/genetics, Genome, Transgenic, Repetitive Sequences, Mice, Models, Neoplasms, Conserved Sequence, ddc:616, Genetics, Mice, Knockout, Base Composition, Multidisciplinary, Sex Chromosomes, Pseudogenes/genetics, Genomics, Multigene Family/genetics, Physical Chromosome Mapping, Neoplasms/genetics, CpG Islands/genetics, Proteome/genetics, Genetic Variation/genetics, Multigene Family, Mice/classification/ genetics, Models, Animal, Conserved Sequence/genetics, Sequence Analysis, Pseudogenes, Human, Genome evolution, Evolution, Sequence analysis, Knockout, Quantitative Trait Loci, Mice, Transgenic, Sex Chromosomes/genetics, Computational biology, Biology, Synteny, Chromosomes, Evolution, Molecular, Nucleic Acid/genetics, Genetic, Species Specificity, Mammalian/ genetics, Animals, Humans, Genes/genetics, Selection, Genetic, Selection, Repetitive Sequences, Nucleic Acid, Comparative genomics, Animal, Genome, Human, Molecular, Genetic Variation, DNA, Sequence Analysis, DNA, Chromosomes, Mammalian, Gene Expression Regulation, Genes, Mutagenesis, RNA, Human genome, CpG Islands, Quantitative Trait Loci/genetics, Reference genome
Abstract

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

Published
2002

23. Correction: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

Author

Lindsay Robertson, Christian von Mering, David Torrents, Paul E. Boardman, Erik Axelsson, Pieter J. deJong, Darren K. Griffin, Ivan Ovcharenko, James K. Bonfield, Tina Graves, Hidetoshi Inoko, Cheryll Tickle, Tracie L. Miner, Kevin J. Beattie, Leo Goodstadt, David W. Burt, John W. Wallis, Richard P. M. A. Crooijmans, Marcia M. Miller, Zissimos Mourelatos, David Speed, Dan Layman, Robert L. Davies, Laura Elnitski, Michael N Romanov, Michael R. Brent, Francesca Chiaromonte, Svitlana Tyekucheva, Jun Wang, Susanne Kerje, Wesley C. Warren, J. J. Emerson, Sergi Castellano, Catrina Fronick, Mary E. Delany, Stuart McLaren, Eduardo Eyras, Kimberly D. Delehaunty, Takashi Shiina, Lucinda Fulton, Michael N. Nhan, Elaine R. Mardis, Mikael Brandström, Patrick Minx, LaDeana W. Hillier, Pavel A. Pevzner, John Douglas Mcpherson, Adam Siepel, David C. King, Lisa Stubbs, Ivica Letunic, Niclas Backström, Hiroshi Arakawa, Maxim Koriabine, Stephen M. J. Searle, Valerie Fillon, Gill Bejerano, Bob Paton, Glenn Tesler, Jessica Severin, Ze Cheng, Leif C. Andersson, Zhirong Bao, David Haussler, Roderic Guigó, Francisco Camara, Sandra W. Clifton, Robert Ivarie, Rick K. Wilson, James C. Kaufman, Mikhail Nefedov, Scott M. Smith, David Shteynberg, Anton Nekrutenko, Mikita Suyama, Jacqueline Smith, Susan Lucas, Arian F.A. Smit, Robert Castelo, Martien A. M. Groenen, Ewan Birney, William Brown, Shiaw-Pyng Yang, Karsten Skjoedt, Lina Jacobbson, Carol Scott, Paul Flicek, Webb Miller, Andrzej M. Kierzek, Yuri Bezzubov, Catherine M. Rondelli, David Morrice, Olivier Pourquié, Stylianos E. Antonarakis, Michael D. R. Croning, Catherine Ucla, Brian J. Raney, Jan Aerts, Jian Wang, Lachlan G. Oddy, Simon J. Hubbard, Peer Bork, Asif T. Chinwalla, Anusha Radakrishnan, Evgeny M. Zdobnov, Artemis G. Hatzigeorgiou, Hans Ellegren, Alain Vignal, Jean-Marie Buerstedde, Matthew T. Webster, Robert S. Harris, Lior Pachter, Henrik Kaessmann, Manyuan Long, Bin Liu, Colin Kremitzki, Pallavi Eswara, Jane Rogers, Evan E. Eichler, Darren Grafham, Jianbin He, D. Waddington, Laurie Gordon, Caleb Webber, W. James Kent, Sam Griffiths-Jones, Gane Ka-Shu Wong, Esther Betrán, Andrew H. Paterson, Sourav Chatterji, Jan J. van der Poel, Nicholas J. Dickens, Terrence S. Furey, Genís Parra, Ian M. Overton, Chris P. Ponting, Randolph B. Caldwell, Sofia Berlin, Isabelle Dupanloup, Rachel A. Harte, Eray Tuzun, Julio S. Masabanda, Matthew D. Francis, Elizabeth J. Huckle, Andy Law, Robert S. Fulton, Kateryna D. Makova, Jan Salomonsen, William E. Nash, Helen G. Tempest, Ross C. Hardison, Sean Humphray, Jerry B. Dodgson, James E. Taylor, Paul F. Cliften, Guillaume Bourque, Monique Rijnkels, Angie S. Hinrichs, Joanne O. Nelson, Josep F. Abril, Colin N. Dewey, Alexandre Reymond, Andrei Kouranov, Craig Pohl, Michael M. Hoffman, Jun Yu, Vincent Magrini, Jacqueline M. Bye, Huanming Yang, Abel Ureta-Vidal, Ruth Taylor, Laura M. Daniels, Shan Yang, Stuart A. Wilson, and Jennifer Randall-Maher

Subjects
Multidisciplinary, biology, Evolutionary biology, biology.animal, Perspective (graphical), Vertebrate, Erratum, Genome, Sequence (medicine)
Published
2005

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