76 posts · 51,259 views
Dan Koboldt is works in the medical genomics group of The Genome Center at Washington University.
Massgenomics
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- May 17, 2012
- 11:26 AM
- 52 views
Genomics, Open Access, and China
by Daniel Koboldt in Massgenomics
The associate editor of the journal Genomics has resigned, stating that he can no longer work for a system that puts profit over access to research. In an article in The Guardian, Winston Hide announced his resignation from “system that provides solid profits for the publisher while effectively denying colleagues in developing countries access to [...]... Read more »
Miller RD, Phillips MS, Jo I, Donaldson MA, Studebaker JF, Addleman N, Alfisi SV, Ankener WM, Bhatti HA, Callahan CE.... (2005) High-density single-nucleotide polymorphism maps of the human genome. Genomics, 86(2), 117-26. PMID: 15961272
- May 11, 2012
- 12:21 PM
- 284 views
Integrating copy number and gene expression data in breast cancer
by Daniel Koboldt in Massgenomics
A study in Nature reports the genomic and transcriptomic architecture of breast cancer from a survey of ~2,000 tumors. These samples were collected in Canada and the UK; what makes the collection particularly valuable is that they were fresh-frozen and clinically annotated, with long-term follow-up. Patients whose tumors were ER-negative and/or lymph-node-positive had received systematic chemotherapy, [...]... Read more »
Curtis, C., Shah, S., Chin, S., Turashvili, G., Rueda, O., Dunning, M., Speed, D., Lynch, A., Samarajiwa, S., Yuan, Y.... (2012) The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. DOI: 10.1038/nature10983
- April 27, 2012
- 12:55 PM
- 88 views
Comparison of Benchtop Sequencers
by Daniel Koboldt in Massgenomics
Working at a major genome center can skew one’s view of the scientific community. You forget, for example, that not every research lab has access to dozens of next-gen sequencers churning out data and an entire building of computing infrastructure to help analyze it. In fact, there’s a very strong market for smaller, cheaper instruments [...]... Read more »
Loman NJ, Misra RV, Dallman TJ, Constantinidou C, Gharbia SE, Wain J, & Pallen MJ. (2012) Performance comparison of benchtop high-throughput sequencing platforms. Nature biotechnology. PMID: 22522955
- April 19, 2012
- 10:22 AM
- 78 views
The genetic architecture of triple-negative breast cancer
by Daniel Koboldt in Massgenomics
Triple-negative breast cancer (TNBC), a tumor type defined by its lack of estrogen receptor, progesterone receptor, and Her2 (ERBB2) amplification, accounts for 16% of breast cancers. This clinically defined tumor type overlaps substantially but not completely with “basal-like” breast cancer, a classification based upon gene expression signature. This is a highly heterogeneous disease with a [...]... Read more »
Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G.... (2012) The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. PMID: 22495314
- April 12, 2012
- 11:33 AM
- 265 views
Fast, Efficient Short Read Alignment with Gaps: Bowtie 2
by Daniel Koboldt in Massgenomics
I’ve always been a fan of Bowtie, one of the first algorithms to leverage Burrows-Wheeler Transform for short read alignment. When I first encountered it in 2008, it was incredibly fast. Faster than Maq and Novoalign, two of the early popular algorithms for read mapping. Perhaps more importantly, it was ultra memory-efficient, enabling one to [...]... Read more »
Langmead B, & Salzberg SL. (2012) Fast gapped-read alignment with Bowtie 2. Nature methods, 9(4), 357-9. PMID: 22388286
- March 30, 2012
- 11:35 AM
- 149 views
Tier 2: Searching for Functional Noncoding Variation
by Daniel Koboldt in Massgenomics
Next-gen sequencing has fundamentally changed the study of human, plant, and animal genetics. For many phenotypes, and inherited diseases in particular, developments in hybridization capture and sequencing technologies have enabled astonishing progress in identifying the variants underlying genetic disorders. Indeed, last year saw dozens of Mendelian diseases solved and numerous cancer types surveyed by exome [...]... Read more »
MacArthur DG, Balasubramanian S, Frankish A, Huang N, Morris J, Walter K, Jostins L, Habegger L, Pickrell JK, Montgomery SB.... (2012) A systematic survey of loss-of-function variants in human protein-coding genes. Science (New York, N.Y.), 335(6070), 823-8. PMID: 22344438
Herdewyn S, Zhao H, Moisse M, Race V, Matthijs G, Reumers J, Kusters B, Schelhaas HJ, van den Berg LH, Goris A.... (2012) Whole-genome sequencing reveals a coding non-pathogenic variant tagging a non-coding pathogenic hexanucleotide repeat expansion in C9orf72 as cause of amyotrophic lateral sclerosis. Human molecular genetics. PMID: 22343411
Spier I, Horpaopan S, Vogt S, Uhlhaas S, Morak M, Stienen D, Draaken M, Ludwig M, Holinski-Feder E, Nöthen MM.... (2012) Deep intronic APC mutations explain a substantial proportion of patients with familial or early onset adenomatous polyposis. Human mutation. PMID: 22431159
- March 14, 2012
- 05:17 PM
- 257 views
Genetic Evolution of Secondary AML from MDS
by Daniel Koboldt in Massgenomics
Myelodysplastic syndromes (MDS) are a group of disorders of ineffective blood production and the most common cause of acquired bone marrow failure in adults. One-third of cases go on to develop secondary AML (sAML), yet there remains uncertainty among patients, insurers, and funding agencies about whether the myelodysplastic syndromes are actually cancers. A study online [...]... Read more »
Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K, Larson DE, McLellan MD, Dooling D, Abbott R.... (2012) Clonal architecture of secondary acute myeloid leukemia. New England Journal of Medicine. info:/
- March 2, 2012
- 11:32 AM
- 278 views
5 Things to Know About SAMtools Mpileup
by Daniel Koboldt in Massgenomics
Next-generation sequencing instruments might be considered a disruptive technology. The incredible throughput of these machines, even 4-5 years ago, clearly mandated the development of a new generation of algorithms and data formats capable of storing, processing, and analyzing huge amounts of sequence data. One key achievement in next-generation sequencing bioinformatics was the specification of sequence [...]... Read more »
Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, & 1000 Genome Project Data Processing Subgroup. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics (Oxford, England), 25(16), 2078-9. PMID: 19505943
- February 16, 2012
- 11:38 AM
- 331 views
Hypomethylation, repressive chromatin, and gene silencing in breast cancer
by Daniel Koboldt in Massgenomics
On the flight to Marco Island I took a stack of papers from Genome Research’s Cancer Issue. One of these is a study of epigenetics in breast cancer by Gary C. Hon and colleagues from the Ludwig Institute for Cancer Research. Hands down, this is one of the best papers I’ve read this year – [...]... Read more »
Hon, G., Hawkins, R., Caballero, O., Lo, C., Lister, R., Pelizzola, M., Valsesia, A., Ye, Z., Kuan, S., Edsall, L.... (2011) Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer. Genome Research, 22(2), 246-258. DOI: 10.1101/gr.125872.111
- February 9, 2012
- 10:38 AM
- 264 views
Immunoediting in Cancer by Exome Sequencing
by Daniel Koboldt in Massgenomics
Cancer immunoediting is a process by which the immune system controls the growth of nascent tumors and shapes their antigenic properties. It’s a sort of catch-22 of cancer biology; by protecting the host from development of cancer, the immune system ultimately selects for tumor cells that are resistant to its attack. Central to the concept [...]... Read more »
Matsushita, H., Vesely, M., Koboldt, D., Rickert, C., Uppaluri, R., Magrini, V., Arthur, C., White, J., Chen, Y., Shea, L.... (2012) Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature. DOI: 10.1038/nature10755
DuPage, M., Mazumdar, C., Schmidt, L., Cheung, A., & Jacks, T. (2012) Expression of tumour-specific antigens underlies cancer immunoediting. Nature. DOI: 10.1038/nature10803
- February 6, 2012
- 11:40 AM
- 713 views
Exome-based Copy Number Analysis with VarScan 2
by Daniel Koboldt in Massgenomics
Now online at Genome Research is the publication of VarScan 2, our in-house algorithm for simultaneous detection of somatic mutations and copy number alterations using exome sequence data from matched tumor-normal pairs. There are a number of reasons why exome-based copy number alteration (CNA) detection should not work. The hybridization process introduces biases, both between [...]... Read more »
Koboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD, Lin L, Miller CA, Mardis ER, Ding L, & Wilson RK. (2012) VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome research. PMID: 22300766
- February 3, 2012
- 01:36 AM
- 625 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
- 438 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
- 543 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
- 426 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
- 542 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
- 251 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
- 234 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
- 1,553 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
- 358 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
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