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Find video protocols related to scientific articles indexed in Pubmed.
Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage.
Science
PUBLISHED: 01-25-2014
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Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.
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Aging as accelerated accumulation of somatic variants: whole-genome sequencing of centenarian and middle-aged monozygotic twin pairs.
Twin Res Hum Genet
PUBLISHED: 11-04-2013
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It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins.
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The zebrafish reference genome sequence and its relationship to the human genome.
Kerstin Howe, Matthew D Clark, Carlos F Torroja, James Torrance, Camille Berthelot, Matthieu Muffato, John E Collins, Sean Humphray, Karen McLaren, Lucy Matthews, Stuart McLaren, Ian Sealy, Mario Caccamo, Carol Churcher, Carol Scott, Jeffrey C Barrett, Romke Koch, Gerd-Jörg Rauch, Simon White, William Chow, Britt Kilian, Leonor T Quintais, José A Guerra-Assunção, Yi Zhou, Yong Gu, Jennifer Yen, Jan-Hinnerk Vogel, Tina Eyre, Seth Redmond, Ruby Banerjee, Jianxiang Chi, Beiyuan Fu, Elizabeth Langley, Sean F Maguire, Gavin K Laird, David Lloyd, Emma Kenyon, Sarah Donaldson, Harminder Sehra, Jeff Almeida-King, Jane Loveland, Stephen Trevanion, Matt Jones, Mike Quail, Dave Willey, Adrienne Hunt, John Burton, Sarah Sims, Kirsten McLay, Bob Plumb, Joy Davis, Chris Clee, Karen Oliver, Richard Clark, Clare Riddle, David Elliot, David Eliott, Glen Threadgold, Glenn Harden, Darren Ware, Sharmin Begum, Beverley Mortimore, Beverly Mortimer, Giselle Kerry, Paul Heath, Benjamin Phillimore, Alan Tracey, Nicole Corby, Matthew Dunn, Christopher Johnson, Jonathan Wood, Susan Clark, Sarah Pelan, Guy Griffiths, Michelle Smith, Rebecca Glithero, Philip Howden, Nicholas Barker, Christine Lloyd, Christopher Stevens, Joanna Harley, Karen Holt, Georgios Panagiotidis, Jamieson Lovell, Helen Beasley, Carl Henderson, Daria Gordon, Katherine Auger, Deborah Wright, Joanna Collins, Claire Raisen, Lauren Dyer, Kenric Leung, Lauren Robertson, Kirsty Ambridge, Daniel Leongamornlert, Sarah McGuire, Ruth Gilderthorp, Coline Griffiths, Deepa Manthravadi, Sarah Nichol, Gary Barker, Siobhan Whitehead, Michael Kay, Jacqueline Brown, Clare Murnane, Emma Gray, Matthew Humphries, Neil Sycamore, Darren Barker, David Saunders, Justene Wallis, Anne Babbage, Sian Hammond, Maryam Mashreghi-Mohammadi, Lucy Barr, Sancha Martin, Paul Wray, Andrew Ellington, Nicholas Matthews, Matthew Ellwood, Rebecca Woodmansey, Graham Clark, James D Cooper, James Cooper, Anthony Tromans, Darren Grafham, Carl Skuce, Richard Pandian, Robert Andrews, Elliot Harrison, Andrew Kimberley, Jane Garnett, Nigel Fosker, Rebekah Hall, Patrick Garner, Daniel Kelly, Christine Bird, Sophie Palmer, Ines Gehring, Andrea Berger, Christopher M Dooley, Zübeyde Ersan-Ürün, Cigdem Eser, Horst Geiger, Maria Geisler, Lena Karotki, Anette Kirn, Judith Konantz, Martina Konantz, Martina Oberländer, Silke Rudolph-Geiger, Mathias Teucke, Christa Lanz, Günter Raddatz, Kazutoyo Osoegawa, Baoli Zhu, Amanda Rapp, Sara Widaa, Cordelia Langford, Fengtang Yang, Stephan C Schuster, Nigel P Carter, Jennifer Harrow, Zemin Ning, Javier Herrero, Steve M J Searle, Anton Enright, Robert Geisler, Ronald H A Plasterk, Charles Lee, Monte Westerfield, Pieter J de Jong, Leonard I Zon, John H Postlethwait, Christiane Nüsslein-Volhard, Tim J P Hubbard, Hugues Roest Crollius, Jane Rogers, Derek L Stemple.
Nature
PUBLISHED: 03-21-2013
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Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
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The draft genome of the fast-growing non-timber forest species moso bamboo (Phyllostachys heterocycla).
Nat. Genet.
PUBLISHED: 02-01-2013
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Bamboo represents the only major lineage of grasses that is native to forests and is one of the most important non-timber forest products in the world. However, no species in the Bambusoideae subfamily has been sequenced. Here, we report a high-quality draft genome sequence of moso bamboo (P. heterocycla var. pubescens). The 2.05-Gb assembly covers 95% of the genomic region. Gene prediction modeling identified 31,987 genes, most of which are supported by cDNA and deep RNA sequencing data. Analyses of clustered gene families and gene collinearity show that bamboo underwent whole-genome duplication 7-12 million years ago. Identification of gene families that are key in cell wall biosynthesis suggests that the whole-genome duplication event generated more gene duplicates involved in bamboo shoot development. RNA sequencing analysis of bamboo flowering tissues suggests a potential connection between drought-responsive and flowering genes.
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The piggyBac transposon displays local and distant reintegration preferences and can cause mutations at noncanonical integration sites.
Mol. Cell. Biol.
PUBLISHED: 01-28-2013
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The DNA transposon piggyBac is widely used as a tool in mammalian experimental systems for transgenesis, mutagenesis, and genome engineering. We have characterized genome-wide insertion site preferences of piggyBac by sequencing a large set of integration sites arising from transposition from two separate genomic loci and a plasmid donor in mouse embryonic stem cells. We found that piggyBac preferentially integrates locally to the excision site when mobilized from a chromosomal location and identified other nonlocal regions of the genome with elevated insertion frequencies. piggyBac insertions were associated with expressed genes and markers of open chromatin structure and were excluded from heterochromatin. At the nucleotide level, piggyBac prefers to insert into TA-rich regions within a broader GC-rich context. We also found that piggyBac can insert into sites other than its known TTAA insertion site at a low frequency (2%). Such insertions introduce mismatches that are repaired with signatures of host cell repair pathways. Transposons could be mobilized from plasmids with the observed noncanonical flanking regions, indicating that piggyBac could generate point mutations in the genome.
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Genetic basis of Y-linked hearing impairment.
Am. J. Hum. Genet.
PUBLISHED: 01-24-2013
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A single Mendelian trait has been mapped to the human Y chromosome: Y-linked hearing impairment. The molecular basis of this disorder is unknown. Here, we report the detailed characterization of the DFNY1 Y chromosome and its comparison with a closely related Y chromosome from an unaffected branch of the family. The DFNY1 chromosome carries a complex rearrangement, including duplication of several noncontiguous segments of the Y chromosome and insertion of ?160 kb of DNA from chromosome 1, in the pericentric region of Yp. This segment of chromosome 1 is derived entirely from within a known hearing impairment locus, DFNA49. We suggest that a third copy of one or more genes from the shared segment of chromosome 1 might be responsible for the hearing-loss phenotype.
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Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species.
Gigascience
PUBLISHED: 01-23-2013
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The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly.
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Mobilization of giant piggyBac transposons in the mouse genome.
Nucleic Acids Res.
PUBLISHED: 09-24-2011
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The development of technologies that allow the stable delivery of large genomic DNA fragments in mammalian systems is important for genetic studies as well as for applications in gene therapy. DNA transposons have emerged as flexible and efficient molecular vehicles to mediate stable cargo transfer. However, the ability to carry DNA fragments >10 kb is limited in most DNA transposons. Here, we show that the DNA transposon piggyBac can mobilize 100-kb DNA fragments in mouse embryonic stem (ES) cells, making it the only known transposon with such a large cargo capacity. The integrity of the cargo is maintained during transposition, the copy number can be controlled and the inserted giant transposons express the genomic cargo. Furthermore, these 100-kb transposons can also be excised from the genome without leaving a footprint. The development of piggyBac as a large cargo vector will facilitate a wider range of genetic and genomic applications.
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Assemblathon 1: a competitive assessment of de novo short read assembly methods.
Genome Res.
PUBLISHED: 09-16-2011
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Low-cost short read sequencing technology has revolutionized genomics, though it is only just becoming practical for the high-quality de novo assembly of a novel large genome. We describe the Assemblathon 1 competition, which aimed to comprehensively assess the state of the art in de novo assembly methods when applied to current sequencing technologies. In a collaborative effort, teams were asked to assemble a simulated Illumina HiSeq data set of an unknown, simulated diploid genome. A total of 41 assemblies from 17 different groups were received. Novel haplotype aware assessments of coverage, contiguity, structure, base calling, and copy number were made. We establish that within this benchmark: (1) It is possible to assemble the genome to a high level of coverage and accuracy, and that (2) large differences exist between the assemblies, suggesting room for further improvements in current methods. The simulated benchmark, including the correct answer, the assemblies, and the code that was used to evaluate the assemblies is now public and freely available from http://www.assemblathon.org/.
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Exploration of signals of positive selection derived from genotype-based human genome scans using re-sequencing data.
Hum. Genet.
PUBLISHED: 08-07-2011
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We have investigated whether regions of the genome showing signs of positive selection in scans based on haplotype structure also show evidence of positive selection when sequence-based tests are applied, whether the target of selection can be localized more precisely, and whether such extra evidence can lead to increased biological insights. We used two tools: simulations under neutrality or selection, and experimental investigation of two regions identified by the HapMap2 project as putatively selected in human populations. Simulations suggested that neutral and selected regions should be readily distinguished and that it should be possible to localize the selected variant to within 40 kb at least half of the time. Re-sequencing of two ~300 kb regions (chr4:158Mb and chr10:22Mb) lacking known targets of selection in HapMap CHB individuals provided strong evidence for positive selection within each and suggested the micro-RNA gene hsa-miR-548c as the best candidate target in one region, and changes in regulation of the sperm protein gene SPAG6 in the other.
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PoolHap: inferring haplotype frequencies from pooled samples by next generation sequencing.
PLoS ONE
PUBLISHED: 01-05-2011
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With the advance of next-generation sequencing (NGS) technologies, increasingly ambitious applications are becoming feasible. A particularly powerful one is the sequencing of polymorphic, pooled samples. The pool can be naturally occurring, as in the case of multiple pathogen strains in a blood sample, multiple types of cells in a cancerous tissue sample, or multiple isoforms of mRNA in a cell. In these cases, its difficult or impossible to partition the subtypes experimentally before sequencing, and those subtype frequencies must hence be inferred. In addition, investigators may occasionally want to artificially pool the sample of a large number of individuals for reasons of cost-efficiency, e.g., when carrying out genetic mapping using bulked segregant analysis. Here we describe PoolHap, a computational tool for inferring haplotype frequencies from pooled samples when haplotypes are known. The key insight into why PoolHap works is that the large number of SNPs that come with genome-wide coverage can compensate for the uneven coverage across the genome. The performance of PoolHap is illustrated and discussed using simulated and real data. We show that PoolHap is able to accurately estimate the proportions of haplotypes with less than 2% error for 34-strain mixtures with 2X total coverage Arabidopsis thaliana whole genome polymorphism data. This method should facilitate greater biological insight into heterogeneous samples that are difficult or impossible to isolate experimentally. Software and users manual are freely available at http://arabidopsis.gmi.oeaw.ac.at/quan/poolhap/.
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Out of the sequencer and into the wiki as we face new challenges in genome informatics.
Genome Biol.
PUBLISHED: 10-28-2010
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A report on the joint Cold Spring Harbor Laboratory/Wellcome Trust Conference Genome Informatics, 15-19 September 2010, Hinxton, Cambridge, UK.
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International network of cancer genome projects.
, Thomas J Hudson, Warwick Anderson, Axel Artez, Anna D Barker, Cindy Bell, Rosa R Bernabé, M K Bhan, Fabien Calvo, Iiro Eerola, Daniela S Gerhard, Alan Guttmacher, Mark Guyer, Fiona M Hemsley, Jennifer L Jennings, David Kerr, Peter Klatt, Patrik Kolar, Jun Kusada, David P Lane, Frank Laplace, Lu Youyong, Gerd Nettekoven, Brad Ozenberger, Jane Peterson, T S Rao, Jacques Remacle, Alan J Schafer, Tatsuhiro Shibata, Michael R Stratton, Joseph G Vockley, Koichi Watanabe, Huanming Yang, Matthew M F Yuen, Bartha M Knoppers, Martin Bobrow, Anne Cambon-Thomsen, Lynn G Dressler, Stephanie O M Dyke, Yann Joly, Kazuto Kato, Karen L Kennedy, Pilar Nicolás, Michael J Parker, Emmanuelle Rial-Sebbag, Carlos M Romeo-Casabona, Kenna M Shaw, Susan Wallace, Georgia L Wiesner, Nikolajs Zeps, Peter Lichter, Andrew V Biankin, Christian Chabannon, Lynda Chin, Bruno Clément, Enrique De Alava, Françoise Degos, Martin L Ferguson, Peter Geary, D Neil Hayes, Amber L Johns, Arek Kasprzyk, Hidewaki Nakagawa, Robert Penny, Miguel A Piris, Rajiv Sarin, Aldo Scarpa, Marc van de Vijver, P Andrew Futreal, Hiroyuki Aburatani, Mònica Bayés, David D L Botwell, Peter J Campbell, Xavier Estivill, Sean M Grimmond, Ivo Gut, Martin Hirst, Carlos Lopez-Otin, Partha Majumder, Marco Marra, John D McPherson, Zemin Ning, Xose S Puente, Yijun Ruan, Hendrik G Stunnenberg, Harold Swerdlow, Victor E Velculescu, Richard K Wilson, Hong H Xue, Liu Yang, Paul T Spellman, Gary D Bader, Paul C Boutros, Paul Flicek, Gad Getz, Roderic Guigo, Guangwu Guo, David Haussler, Simon Heath, Tim J Hubbard, Tao Jiang, Steven M Jones, Qibin Li, Nuria López-Bigas, Ruibang Luo, Lakshmi Muthuswamy, B F Francis Ouellette, John V Pearson, Víctor Quesada, Benjamin J Raphael, Chris Sander, Terence P Speed, Lincoln D Stein, Joshua M Stuart, Jon W Teague, Yasushi Totoki, Tatsuhiko Tsunoda, Alfonso Valencia, David A Wheeler, Honglong Wu, Shancen Zhao, Guangyu Zhou, Mark Lathrop, Gilles Thomas, Teruhiko Yoshida, Myles Axton, Chris Gunter, Linda J Miller, Junjun Zhang, Syed A Haider, Jianxin Wang, Christina K Yung, Anthony Cros, Anthony Cross, Yong Liang, Saravanamuttu Gnaneshan, Jonathan Guberman, Jack Hsu, Don R C Chalmers, Karl W Hasel, Terry S H Kaan, William W Lowrance, Tohru Masui, Laura Lyman Rodriguez, Catherine Vergely, David D L Bowtell, Nicole Cloonan, Anna deFazio, James R Eshleman, Dariush Etemadmoghadam, Brooke B Gardiner, Brooke A Gardiner, James G Kench, Robert L Sutherland, Margaret A Tempero, Nicola J Waddell, Peter J Wilson, Steve Gallinger, Ming-Sound Tsao, Patricia A Shaw, Gloria M Petersen, Debabrata Mukhopadhyay, Ronald A DePinho, Sarah Thayer, Kamran Shazand, Timothy Beck, Michelle Sam, Lee Timms, Vanessa Ballin, Youyong Lu, Jiafu Ji, Xiuqing Zhang, Feng Chen, Xueda Hu, Qi Yang, Geng Tian, Lianhai Zhang, Xiaofang Xing, Xianghong Li, Zhenggang Zhu, Yingyan Yu, Jun Yu, Jörg Tost, Paul Brennan, Ivana Holcatova, David Zaridze, Alvis Brazma, Lars Egevard, Egor Prokhortchouk, Rosamonde Elizabeth Banks, Mathias Uhlén, Juris Viksna, Fredrik Ponten, Konstantin Skryabin, Ewan Birney, Ake Borg, Anne-Lise Børresen-Dale, Carlos Caldas, John A Foekens, Sancha Martin, Jorge S Reis-Filho, Andrea L Richardson, Christos Sotiriou, Giles Thoms, Laura van't Veer, Daniel Birnbaum, Hélène Blanché, Pascal Boucher, Sandrine Boyault, Jocelyne D Masson-Jacquemier, Iris Pauporté, Xavier Pivot, Anne Vincent-Salomon, Eric Tabone, Charles Theillet, Isabelle Treilleux, Paulette Bioulac-Sage, Thomas Decaens, Dominique Franco, Marta Gut, Didier Samuel, Jessica Zucman-Rossi, Roland Eils, Benedikt Brors, Jan O Korbel, Andrey Korshunov, Pablo Landgraf, Hans Lehrach, Stefan Pfister, Bernhard Radlwimmer, Guido Reifenberger, Michael D Taylor, Christof von Kalle, Partha P Majumder, Paolo Pederzoli, Rita A Lawlor, Massimo Delledonne, Alberto Bardelli, Thomas Gress, David Klimstra, Giuseppe Zamboni, Yusuke Nakamura, Satoru Miyano, Akihiro Fujimoto, Elias Campo, Silvia de Sanjosé, Emili Montserrat, Marcos Gonzalez-Díaz, Pedro Jares, Heinz Himmelbauer, Heinz Himmelbaue, Sílvia Beà, Samuel Aparicio, Douglas F Easton, Francis S Collins, Carolyn C Compton, Eric S Lander, Wylie Burke, Anthony R Green, Stanley R Hamilton, Olli P Kallioniemi, Timothy J Ley, Edison T Liu, Brandon J Wainwright.
Nature
PUBLISHED: 04-16-2010
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The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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A comprehensive catalogue of somatic mutations from a human cancer genome.
Nature
PUBLISHED: 07-30-2009
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All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.
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Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels.
Genome Biol.
PUBLISHED: 07-05-2009
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Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived strain A/J, and the Mus musculus castaneus derived strain CAST/Ei. We describe approaches for the accurate identification of nucleotide and structural variation in the genomes of vertebrate experimental organisms, and show how these techniques can be applied to help prioritize candidate genes within quantitative trait loci.
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HI: haplotype improver using paired-end short reads.
Bioinformatics
PUBLISHED: 07-01-2009
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We present a program to improve haplotype reconstruction by incorporating information from paired-end reads, and demonstrate its utility on simulated data. We find that given a fixed coverage, longer reads (implying fewer of them) are preferable.
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Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads.
Bioinformatics
PUBLISHED: 06-26-2009
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There is a strong demand in the genomic community to develop effective algorithms to reliably identify genomic variants. Indel detection using next-gen data is difficult and identification of long structural variations is extremely challenging.
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Amplification-free Illumina sequencing-library preparation facilitates improved mapping and assembly of (G+C)-biased genomes.
Nat. Methods
PUBLISHED: 02-17-2009
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Amplification artifacts introduced during library preparation for the Illumina Genome Analyzer increase the likelihood that an appreciable proportion of these sequences will be duplicates and cause an uneven distribution of read coverage across the targeted sequencing regions. As a consequence, these unfavorable features result in difficulties in genome assembly and variation analysis from the short reads, particularly when the sequences are from genomes with base compositions at the extremes of high or low G+C content. Here we present an amplification-free method of library preparation, in which the cluster amplification step, rather than the PCR, enriches for fully ligated template strands, reducing the incidence of duplicate sequences, improving read mapping and single nucleotide polymorphism calling and aiding de novo assembly. We illustrate this by generating and analyzing DNA sequences from extremely (G+C)-poor (Plasmodium falciparum), (G+C)-neutral (Escherichia coli) and (G+C)-rich (Bordetella pertussis) genomes.
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Assessing the gene space in draft genomes.
Nucleic Acids Res.
PUBLISHED: 02-04-2009
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Genome sequencing projects have been initiated for a wide range of eukaryotes. A few projects have reached completion, but most exist as draft assemblies. As one of the main reasons to sequence a genome is to obtain its catalog of genes, an important question is how complete or completable the catalog is in unfinished genomes. To answer this question, we have identified a set of core eukaryotic genes (CEGs), that are extremely highly conserved and which we believe are present in low copy numbers in higher eukaryotes. From an analysis of a phylogenetically diverse set of eukaryotic genome assemblies, we found that the proportion of CEGs mapped in draft genomes provides a useful metric for describing the gene space, and complements the commonly used N50 length and x-fold coverage values.
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The genome of the blood fluke Schistosoma mansoni.
Nature
PUBLISHED: 01-18-2009
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Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
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Next-generation sequencing and large genome assemblies.
Pharmacogenomics
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The next-generation sequencing (NGS) revolution has drastically reduced time and cost requirements for sequencing of large genomes, and also qualitatively changed the problem of assembly. This article reviews the state of the art in de novo genome assembly, paying particular attention to mammalian-sized genomes. The strengths and weaknesses of the main sequencing platforms are highlighted, leading to a discussion of assembly and the new challenges associated with NGS data. Current approaches to assembly are outlined and the various software packages available are introduced and compared. The question of whether quality assemblies can be produced using short-read NGS data alone, or whether it must be combined with more expensive sequencing techniques, is considered. Prospects for future assemblers and tests of assembly performance are also discussed.
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Expansion of CORE-SINEs in the genome of the Tasmanian devil.
BMC Genomics
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The genome of the carnivorous marsupial, the Tasmanian devil (Sarcophilus harrisii, Order: Dasyuromorphia), was sequenced in the hopes of finding a cure for or gaining a better understanding of the contagious devil facial tumor disease that is threatening the species survival. To better understand the Tasmanian devil genome, we screened it for transposable elements and investigated the dynamics of short interspersed element (SINE) retroposons.
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Insights into hominid evolution from the gorilla genome sequence.
Nature
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Gorillas are humans closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.
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Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer.
Cell
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The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.
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PASSion: a pattern growth algorithm-based pipeline for splice junction detection in paired-end RNA-Seq data.
Bioinformatics
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RNA-seq is a powerful technology for the study of transcriptome profiles that uses deep-sequencing technologies. Moreover, it may be used for cellular phenotyping and help establishing the etiology of diseases characterized by abnormal splicing patterns. In RNA-Seq, the exact nature of splicing events is buried in the reads that span exon-exon boundaries. The accurate and efficient mapping of these reads to the reference genome is a major challenge.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.