65 posts · 35,548 views
Dan Koboldt blogs about human genetics, genomics, and DNA sequencing in the post-genome era.
Daniel Koboldt
65 posts
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- February 3, 2012
- 01:36 AM
- 42 views
Recurrent histone alterations in pediatric brain cancer
by Daniel Koboldt in Massgenomics
Brain tumors are a particularly deadly form of cancer, and the leading cause of cancer-related death in children. Two studies published this week in Nature journals applied next-generation sequencing to pediatric brain tumors, revealing a striking pattern of recurrent somatic mutations in H3F3A, a gene encoding the histone prorein H3.3. These are the first unbiased [...]... Read more »
Schwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DA, Tönjes M.... (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. PMID: 22286061
St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project, Wu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J, Qu C, Ding L, Huether R.... (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nature genetics. PMID: 22286216
- January 24, 2012
- 01:30 AM
- 209 views
The Current State of dbSNP
by Daniel Koboldt in Massgenomics
Less than a decade ago, the leading experts estimated that there were approximately 10 million SNPs in the human genome. Those were the early days of post-genome research, when “The SNP Consortium” was formed and began BAC overlap comparisons to routinely identify and report SNPs. Believe it or not, in my old lab there were [...]... Read more »
Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, & Sirotkin K. (2001) dbSNP: the NCBI database of genetic variation. Nucleic acids research, 29(1), 308-11. PMID: 11125122
- January 18, 2012
- 06:18 PM
- 66 views
Genomic Structural Variation: Methods & Protocols
by Daniel Koboldt in Massgenomics
The draft human genome sequence, completed more than a decade ago, was an important starting point for understanding genetic variation in humans. Intensive efforts to characterize single-nucleotide polymoprhisms (SNPs), and later the discovery of extensive copy number variation (CNV) and structural variation, have highlighted the complex and dynamic nature of the our genome. Earlier this [...]... Read more »
Levy RJ, Xu B, Gogos JA, & Karayiorgou M. (2012) Copy number variation and psychiatric disease risk. Methods in molecular biology (Clifton, N.J.), 97-113. PMID: 22228008
Johansson AC, & Feuk L. (2012) Characterizing and interpreting genetic variation from personal genome sequencing. Methods in molecular biology (Clifton, N.J.), 343-67. PMID: 22228021
Koboldt DC, Larson DE, Chen K, Ding L, & Wilson RK. (2012) Massively parallel sequencing approaches for characterization of structural variation. Methods in molecular biology (Clifton, N.J.), 369-84. PMID: 22228022
Marshall CR, & Scherer SW. (2012) Detection and characterization of copy number variation in autism spectrum disorder. Methods in molecular biology (Clifton, N.J.), 115-35. PMID: 22228009
- January 13, 2012
- 10:22 AM
- 80 views
A Tumor Evolved: Relapsed Acute Myeloid Leukemia
by Daniel Koboldt in Massgenomics
Acute myeloid leukemia (AML) is a cancer of myeloid blood cells, in which abnormal white blood cells accumulate in the bone marrow and interfere with normal blood cell production. This is a highly malignant tumor affecting 13,000 adults in the United States each year; if left untreated, it progresses rapidly and leads to death within [...]... Read more »
Ding, L., Ley, T., Larson, D., Miller, C., Koboldt, D., Welch, J., Ritchey, J., Young, M., Lamprecht, T., McLellan, M.... (2012) Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. DOI: 10.1038/nature10738
- January 12, 2012
- 01:21 AM
- 73 views
Genetic Basis of an Aggressive Pediatric Leukemia
by Daniel Koboldt in Massgenomics
Contents: Early T-cell ALL • Whole-genome Sequencing • Genetic Architecture of ETP-ALL • A Stem-cell Leukemia Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, comprising two forms: B-cell ALL (85% of cases) and T-cell ALL (15% of cases). In this week’s issue of Nature, Jinghui Zhang and colleagues report the whole-genome sequencing of [...]... Read more »
Zhang, J., Ding, L., Holmfeldt, L., Wu, G., Heatley, S., Payne-Turner, D., Easton, J., Chen, X., Wang, J., Rusch, M.... (2012) The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature, 481(7380), 157-163. DOI: 10.1038/nature10725
- January 5, 2012
- 01:53 PM
- 81 views
Cancer Genome and Exome Sequencing in 2011
by Daniel Koboldt in Massgenomics
As a follow-up to my previous post, Disease-causing Mutations Discovered by NGS in 2011, I’ve attempted to compile cancer genome and exome sequencing studies published last year. For this compilation, I’ve emphasized publications in which whole-genome or exome sequencing was employed to multiple tumors or cancer cell lines, with the goal of identifying significantly altered [...]... Read more »
Ding L, Wendl MC, Koboldt DC, & Mardis ER. (2010) Analysis of next-generation genomic data in cancer: accomplishments and challenges. Human molecular genetics, 19(R2). PMID: 20843826
- December 29, 2011
- 01:04 PM
- 75 views
Disease-causing Mutations Discovered by NGS in 2011
by Daniel Koboldt in Massgenomics
The number of human genetic diseases unraveled by next-generation sequencing skyrocketed this year. Several factors contributed to this growth, two of which were the ever-increasing throughput of sequencing instruments and widespread availability of commercial exome platforms. A number of large-scale initiatives to discovery disease genes by exome sequencing, particularly for Mendelian disorders, got off the [...]... Read more »
Shendure, J. (2011) Next-generation human genetics. Genome Biology, 12(9), 408. DOI: 10.1186/gb-2011-12-9-408
- December 15, 2011
- 09:58 AM
- 554 views
Recurrent splicing mutations in MDS and leukemia
by Daniel Koboldt in Massgenomics
Myelodysplastic syndrome (MDS, also called preleukemia) is a blood disorder characterized by ineffective production of myeloid cells, or leukocytes. The disorderly and ineffective production of blood cells from stem cells in the bone marrow results in low blood counts, or cytopenias. As many of 30% of MDS cases progress to full-blown, chemotherapy-resistant secondary AML. This [...]... Read more »
Graubert TA, Shen D, Ding L, Okeyo-Owuor T, Lunn CL, Shao J, Krysiak K, Harris CC, Koboldt DC, Larson DE.... (2011) Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nature genetics. PMID: 22158538
Quesada V, Conde L, Villamor N, Ordóñez GR, Jares P, Bassaganyas L, Ramsay AJ, Beà S, Pinyol M, Martínez-Trillos A.... (2011) Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nature genetics. PMID: 22158541
- December 8, 2011
- 06:13 PM
- 181 views
Somatic Mutation Detection in Whole Genome Sequencing Data
by Daniel Koboldt in Massgenomics
A paper online at Bioinformatics describes our flagship algorithm for detecting somatic point mutations in whole-genome sequencing of tumor samples. This freely available software package, called SomaticSniper, performs a Bayesian comparison of the genotype likelihoods in tumor and normal samples at every [covered] position in the genome. Overview Documentation Install The study includes a detailed [...]... Read more »
Larson, DE., Harris, CC., Chen, K., Koboldt, DC., Abbott, TE., Dooling, DJ., Ley, TJ., Mardis, ER., Wilson, RK., & Ding, L. (2011) SomaticSniper: Identification of Somatic Point Mutations in Whole Genome Sequencing Data. Bioinformatics, 1. info:/doi: 10.1093/bioinformatics/btr665
- November 29, 2011
- 06:03 PM
- 130 views
Prostate cancer exomes, and sequencing matched normals
by Daniel Koboldt in Massgenomics
A new study in PNAS from Jay Shendure’s group at the University of Washington describes exome sequencing of 23 prostate cancers. These tumors were derived from aggressive primary tumors or lethal metastases, and propagated in immunocompromised mice as xenografts. For most of the tumors, matched normal DNA was unavailable, so the authors developed a filtering [...]... Read more »
Kumar A, White TA, MacKenzie AP, Clegg N, Lee C, Dumpit RF, Coleman I, Ng SB, Salipante SJ, Rieder MJ.... (2011) Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers. Proceedings of the National Academy of Sciences of the United States of America, 108(41), 17087-92. PMID: 21949389
- October 26, 2011
- 12:09 PM
- 86 views
Major Exome Platforms Compared
by Daniel Koboldt in Massgenomics
A few recent studies have sought to compare commercial exome sequencing technologies. These kits, which selectively target coding regions for next-generation sequencing, have matured rapidly over the past couple of years. I like the recent study out of Michael Snyder’s lab (Stanford)the best. In it, the authors compared three major exome platforms – Agilent’s SureSelect [...]... Read more »
Clark MJ, Chen R, Lam HY, Karczewski KJ, Chen R, Euskirchen G, Butte AJ, & Snyder M. (2011) Performance comparison of exome DNA sequencing technologies. Nature biotechnology, 29(10), 908-14. PMID: 21947028
- September 16, 2011
- 11:32 AM
- 97 views
Whole-genome sequencing and clinical annotation
by Daniel Koboldt in Massgenomics
Next-generation sequencing has immense transformative potential for medicine in the coming decade. Rapid, economical whole-genome sequencing can provide a wealth of information useful for diagnosis, treatment, and even prevention of disease. Very soon (if not already), generating whole-genome sequencing data will be routine. The challenges will lie in accurate variant calling, phasing, annotation, and clinical [...]... Read more »
Frederick E. Dewey, Rong Chen, Sergio P. Cordero, Kelly E. Ormond, Colleen Caleshu, Konrad J. Karczewski, Michelle Whirl-Carrillo, Matthew T. Wheeler, Joel T. Dudley, Jake K. Byrnes, Omar E. Cornejo, Joshua W. Knowles, Mark Woon, Katrin Sangkuhl, Li Gong,, Madeleine P. Ball, Alexander W. Zaranek, Heidi L. Rehm, George M. Church, John S. West, Carlos D. Bustamante, Michael Snyder, Russ B. Altman, Teri E. Klein.... (2011) Phased whole genome genetic risk in a family quartet using a major allele reference sequence. PLoS Genetics, 7(9). info:/
- August 26, 2011
- 04:47 PM
- 378 views
A Guide for Deep Sequencing of Human Genomes
by Daniel Koboldt in Massgenomics
The incredible throughput of current second-generation sequencing platforms makes it possible to sequence a complete human genome to high coverage, with a single instrument run, in less than 2 weeks. As whole-genome sequencing becomes more routine, it is increasingly important to understand the accuracy of sequence-level analyses, such as SNP detection, and its relationship to [...]... Read more »
Ajay SS, Parker SC, Ozel Abaan H, Fuentes Fajardo KV, & Margulies EH. (2011) Accurate and comprehensive sequencing of personal genomes. Genome research. PMID: 21771779
- August 9, 2011
- 11:59 AM
- 372 views
NOTCH tumor suppression in HNSCC
by Daniel Koboldt in Massgenomics
More than half a million new cases of head and neck squamous cell carcinoma (HNSCC) will occur in 2011, making it the 6th most common malignancy in the world. Two studies online at the journal Science survey the mutational landscape of this deadly cancer, which has a mortality rate of ~50%. They report frequent mutation [...]... Read more »
Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence M, Sougnez C, McKenna A.... (2011) The Mutational Landscape of Head and Neck Squamous Cell Carcinoma. Science (New York, N.Y.). PMID: 21798893
Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J.... (2011) Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1. Science (New York, N.Y.). PMID: 21798897
- June 10, 2011
- 12:28 PM
- 360 views
Recurrent mutations in chronic lymphocytic leukemia
by Daniel Koboldt in Massgenomics
A study published online at Nature reports the identification of three recurrently mutated genes by whole-genome sequencing of four cases with chronic lymphocytic leukemia (CLL). This is the most common adult leukemia in western nations, with two major subtypes distinguished by somatic hypermutation of the immunoglobulin heavy chain (IgH) variable region. Led by [...]... Read more »
Puente XS, Pinyol M, Quesada V, Conde L, Ordóñez GR, Villamor N, Escaramis G, Jares P, Beà S, González-Díaz M.... (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature. PMID: 21642962
Mardis, E., Ding, L., Dooling, D., Larson, D., McLellan, M., Chen, K., Koboldt, D., Fulton, R., Delehaunty, K., McGrath, S.... (2009) Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome. New England Journal of Medicine, 361(11), 1058-1066. DOI: 10.1056/NEJMoa0903840
Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M.... (2008) DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature, 456(7218), 66-72. PMID: 18987736
- May 27, 2011
- 01:30 PM
- 553 views
A virus-associated liver cancer genome
by Daniel Koboldt in Massgenomics
In Nature Genetics last month, Yasushi Totoki and colleagues present the high-resolution characterization of hepatocellular carcinoma (HCC), the third most frequent cause of cancer-related death worldwide. The authors performed whole-genome sequencing (Illumina 2×50 bp) of the primary tumor (36x) and matched lymphocytes (28x) from a Japanese male with hepatitis C virus-positive liver cancer.
The epidemiology of [...]... Read more »
Totoki Y, Tatsuno K, Yamamoto S, Arai Y, Hosoda F, Ishikawa S, Tsutsumi S, Sonoda K, Totsuka H, Shirakihara T.... (2011) High-resolution characterization of a hepatocellular carcinoma genome. Nature genetics, 43(5), 464-9. PMID: 21499249
Wei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J, Davis S, NISC Comparative Sequencing Program, Stemke-Hale K, Davies MA.... (2011) Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nature genetics, 43(5), 442-6. PMID: 21499247
- May 13, 2011
- 12:53 PM
- 545 views
Inflammation, Genetic Instability, and Cancer
by Daniel Koboldt in Massgenomics
Inflammation was first linked to cancer in the 1863 by Rudolf Virchow, who observed that inflammatory cells were present in tumor biopsy specimens, and tumors often developed at sites of chronic inflammation. Investigations into this connection waned over the next century, and only recently have seen a resurgence of interest. A slew of new evidence [...]... Read more »
David W. Kamp, Emily Shacter, Sigmund A. Weitzman. (2011) Chronic Inflammation and Cancer: The Role of the Mitochondria. ONCOLOGY, 25(5). info:/
Colotta F, Allavena P, Sica A, Garlanda C, & Mantovani A. (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis, 30(7), 1073-81. PMID: 19468060
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) Cancer-related inflammation. Nature, 454(7203), 436-444. DOI: 10.1038/nature07205
- April 28, 2011
- 10:58 AM
- 560 views
Genome sequencing of multiple myeloma
by Daniel Koboldt in Massgenomics
A recent study in Nature reports an initial view of the genome of multiple myeloma (MMY), an incurable cancer of plasma cells (B cells) in the blood. Though it is the second most common hematological malignancy, MMY remains poorly understood. Some 40% of cases harbor structural alterations that place genes in [...]... Read more »
Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP, Ahmann GJ, Adli M.... (2011) Initial genome sequencing and analysis of multiple myeloma. Nature, 471(7339), 467-72. PMID: 21430775
- April 22, 2011
- 10:46 AM
- 545 views
Whole-Genome Sequencing for Cancer Patients
by Daniel Koboldt in Massgenomics
Two studies published in JAMA reveal the power of whole-genome sequencing improve the diagnosis and treatment of cancer. Both are from collaborations of the Genome Institute and the School of Medicine at Washington University in St. Louis, Missouri. First, Link and colleagues report the identification of a novel cancer susceptibility mutation (a 3-kbp deletion in [...]... Read more »
Link DC, Schuettpelz LG, Shen D, Wang J, Walter MJ, Kulkarni S, Payton JE, Ivanovich J, Goodfellow PJ, Le Beau M.... (2011) Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA : the journal of the American Medical Association, 305(15), 1568-76. PMID: 21505135
Welch JS, Westervelt P, Ding L, Larson DE, Klco JM, Kulkarni S, Wallis J, Chen K, Payton JE, Fulton RS.... (2011) Use of whole-genome sequencing to diagnose a cryptic fusion oncogene. JAMA : the journal of the American Medical Association, 305(15), 1577-84. PMID: 21505136
- April 1, 2011
- 12:55 PM
- 672 views
The Cancer Methylome by MeDIP-Seq
by Daniel Koboldt in Massgenomics
Human cancers are driven by genetic and epigenetic changes to the genome of healthy cells. We often think about acquired mutations as the key drivers of tumor development and growth. Most studies empowered by next-gen sequencing have focused on identifying these changes. Yet aberrant DNA methylation - hypermethylation of tumor suppressor genes and hypomethylation of [...]... Read more »
Feber A, Wilson GA, Zhang L, Presneau N, Idowu B, Down TA, Rakyan VK, Noon LA, Lloyd AC, Stupka E.... (2011) Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors. Genome research. PMID: 21324880
Down TA, Rakyan VK, Turner DJ, Flicek P, Li H, Kulesha E, Gräf S, Johnson N, Herrero J, Tomazou EM.... (2008) A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis. Nature biotechnology, 26(7), 779-85. PMID: 18612301
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