Research Topics
Genomes and Genes | Chad NusbaumSummaryAffiliation: Massachusetts Institute of Technology Country: USA Publications
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Publications
DNA sequence and analysis of human chromosome 8Chad Nusbaum
Broad Institute of MIT and Harvard, 320 Charles St, Cambridge, Massachusetts 02141, USA
Nature 439:331-5. 2006..The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution...
Genome-scale DNA methylation maps of pluripotent and differentiated cellsAlexander Meissner
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 454:766-70. 2008..More generally, the results establish reduced representation bisulphite sequencing as a powerful technology for epigenetic profiling of cell populations relevant to developmental biology, cancer and regenerative medicine...
Model-based analysis of ChIP-Seq (MACS)Yong Zhang
Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA
Genome Biol 9:R137. 2008..MACS also uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions. MACS compares favorably to existing ChIP-Seq peak-finding algorithms, and is freely available...
Short-term genome evolution of Listeria monocytogenes in a non-controlled environmentRenato H Orsi
Department of Food Science, Cornell University, Ithaca, NY, USA
BMC Genomics 9:539. 2008..While a genome sequence for the 1988 food isolate has been reported, we sequenced the genomes of the 1988 human isolate as well as a human and a food isolate from the 2000 outbreak to allow for comparative genome analyses...
DNA sequence and analysis of human chromosome 18Chad Nusbaum
Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, Massachusetts 02141, USA
Nature 437:551-5. 2005..This has important implications for the nature and roles of non-protein-coding sequence elements...
Analysis of the DNA sequence and duplication history of human chromosome 15Michael C Zody
Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, Massachusetts 02141, USA
Nature 440:671-5. 2006..Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome...
Integrative analysis of the melanoma transcriptomeMichael F Berger
The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Genome Res 20:413-27. 2010..Taken together, these results may indicate new avenues for target discovery in melanoma, while also providing a template for large-scale transcriptome studies across many tumor types...
Finished bacterial genomes from shotgun sequence dataFilipe J Ribeiro
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Genome Res 22:2270-7. 2012..Cost and time requirements are thus dramatically reduced...
Full-length transcriptome assembly from RNA-Seq data without a reference genomeManfred G Grabherr
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA
Nat Biotechnol 29:644-52. 2011..Our approach provides a unified solution for transcriptome reconstruction in any sample, especially in the absence of a reference genome...
High-quality draft assemblies of mammalian genomes from massively parallel sequence dataSante Gnerre
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Proc Natl Acad Sci U S A 108:1513-8. 2011..The ALLPATHS-LG program is available at http://www.broadinstitute.org/science/programs/genome-biology/crd...
Comprehensive comparative analysis of strand-specific RNA sequencing methodsJoshua Z Levin
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA
Nat Methods 7:709-15. 2010..Our analysis provides a comprehensive benchmark, and our computational pipeline is applicable for assessment of future protocols in other organisms...
Strand-specific RNA sequencing reveals extensive regulated long antisense transcripts that are conserved across yeast speciesMoran Yassour
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Genome Biol 11:R87. 2010..However, the functional role of antisense transcripts has been demonstrated only in a few cases and it has been suggested that most antisense transcripts may result from promiscuous bi-directional transcription in a dense genome...
Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencingAndreas Gnirke
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Biotechnol 27:182-9. 2009..One lane of Illumina sequence was sufficient to call high-confidence genotypes for 89% of the targeted exon space...
Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAsMitchell Guttman
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
Nat Biotechnol 28:503-10. 2010..Our results open the way to direct experimental manipulation of thousands of noncoding RNAs and demonstrate the power of ab initio reconstruction to render a comprehensive picture of mammalian transcriptomes...
Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cellsMichal Rabani
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
Nat Biotechnol 29:436-42. 2011..Certain transcripts, including those encoding cytokines and transcription factors, mature faster. Our study provides a quantitative approach to study the integrative process of RNA regulation...
A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammalsManuel Garber
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Mol Cell 47:810-22. 2012....
Analyzing and minimizing PCR amplification bias in Illumina sequencing librariesDaniel Aird
Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA
Genome Biol 12:R18. 2011..Our improved protocol significantly reduces amplification bias and minimizes the previously severe effects of PCR instrument and temperature ramp rate...
Quality scores and SNP detection in sequencing-by-synthesis systemsWilliam Brockman
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA
Genome Res 18:763-70. 2008..We demonstrate good specificity in single reads, and excellent specificity (no false positives in 215 kb of genome) in high-coverage data...
Paired-end sequencing of Fosmid libraries by IlluminaLouise J S Williams
Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA
Genome Res 22:2241-9. 2012..Our Fosill-powered assembly of the mouse genome has an N50 scaffold length of 17.0 Mb, rivaling the connectivity (16.9 Mb) of the Sanger-sequencing based draft assembly...
Hybrid selection for sequencing pathogen genomes from clinical samplesAlexandre Melnikov
Genome Sequencing and Analysis Program, Broad Institute, Cambridge, MA 02142, USA
Genome Biol 12:R73. 2011..This approach will enable efficient genome sequencing of pathogens from clinical samples, as well as sequencing of endosymbiotic organisms such as Wolbachia that live inside diverse metazoan phyla...
A scalable, fully automated process for construction of sequence-ready human exome targeted capture librariesSheila Fisher
Genome Sequencing Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA
Genome Biol 12:R1. 2011..Significant process improvements and a series of in-process quality control checkpoints are also added. These process improvements can also be used in a manual version of the protocol...
A high-resolution map of human evolutionary constraint using 29 mammalsKerstin Lindblad-Toh
Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 478:476-82. 2011..Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease...
Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcriptsJoshua Z Levin
Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, MA 02141, USA
Genome Biol 10:R115. 2009..Thus, targeted RNA-Seq produces an enhanced view of the molecular state of a set of "high interest" genes...
Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestansBrian J Haas
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA
Nature 461:393-8. 2009..infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential...
Closing gaps in the human genome using sequencing by synthesisManuel Garber
Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Genome Biol 10:R60. 2009..We present an approach for closing these gaps using 454 sequencing. As a proof of principle, we closed all three remaining non-structural gaps in chromosome 15...
High-resolution mapping of copy-number alterations with massively parallel sequencingDerek Y Chiang
Broad Institute, Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA
Nat Methods 6:99-103. 2009....
A scalable, fully automated process for construction of sequence-ready barcoded libraries for 454Niall J Lennon
Genome Sequencing Platform, Broad Institute of MIT and Harvard, 320 Charles St, Cambridge, MA 02141, USA
Genome Biol 11:R15. 2010..Using this methodology, one technician can create 96 sequence-ready 454 libraries in 2 days, a dramatic improvement over the standard method...
ALLPATHS 2: small genomes assembled accurately and with high continuity from short paired readsIain MacCallum
Broad Institute of MIT and Harvard, Charles Street, Cambridge, MA 02141, USA
Genome Biol 10:R103. 2009..Velvet and EULER-SR were less accurate. For example, for Escherichia coli, the fraction of 10-kb stretches that were perfect was 99.8% (ALLPATHS2), 68.7% (Velvet), and 42.1% (EULER-SR)...
DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineageMichael C Zody
Broad Institute of MIT and Harvard, 7 Cambridge Center, Massachusetts 02142, USA
Nature 440:1045-9. 2006..Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome...
Sensitive, specific polymorphism discovery in bacteria using massively parallel sequencingChad Nusbaum
Broad Institute of Massachusetts Institute of Technology and Harvard University, 320 Charles Street, Cambridge, MA 02141, USA
Nat Methods 6:67-9. 2009..VAAL also pinpointed a single mutation between Vibrio cholerae genomes, identifying an antibiotic's site of action by identifying sequence differences between drug-sensitive strains and drug-resistant derivatives...
Pacific biosciences sequencing technology for genotyping and variation discovery in human dataMauricio O Carneiro
Broad Institute of MIT and Harvard, Medical and Population Genetics Program, Cambridge, MA 02141, USA
BMC Genomics 13:375. 2012..With these potential advantages in mind, we here evaluate the utility of the Pacific Biosciences RS platform for human medical amplicon resequencing projects...
How deep is deep enough for RNA-Seq profiling of bacterial transcriptomes?Brian J Haas
Genome Sequencing and Analysis Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
BMC Genomics 13:734. 2012..A central challenge in designing RNA-Seq-based experiments is estimating a priori the number of reads per sample needed to detect and quantify thousands of individual transcripts with a large dynamic range of abundance...
Efficient and robust RNA-seq process for cultured bacteria and complex community transcriptomesGeorgia Giannoukos
Genome Sequencing and Analysis Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA
Genome Biol 13:R23. 2012..The resulting expression profiles were highly reproducible, enriched up to 40-fold for non-rRNA transcripts, and correlated well with profiles representing undepleted total RNA...
ALLPATHS: de novo assembly of whole-genome shotgun microreadsJonathan Butler
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA
Genome Res 18:810-20. 2008..We describe a general method for genome assembly that can be applied to all types of DNA sequence data, not only short read data, but also conventional sequence reads...
Mammalian microRNAs: experimental evaluation of novel and previously annotated genesH Rosaria Chiang
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
Genes Dev 24:992-1009. 2010....
Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencingAndrew Kirby
Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Nat Genet 45:299-303. 2013..These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing...
The genome sequence of the filamentous fungus Neurospora crassaJames E Galagan
Whitehead Institute Center for Genome Research, 320 Charles Street, Cambridge, Massachusetts 02141, USA
Nature 422:859-68. 2003..Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes...
Increasing ecological inference from high throughput sequencing of fungi in the environment through a tagging approachD Lee Taylor
Institute of Arctic Biology, 311 Irving I Building, University of Alaska, Fairbanks, AK 99775, USA, Broad Institute, Massachusetts Institute of Technology, 320 Charles Street, Cambridge, MA 02141, USA
Mol Ecol Resour 8:742-52. 2008..Similar results were obtained using UniFrac phylogenetic comparisons. Together, these results suggest that the pig-tagged primers can be used to increase ecological inference in high throughput sequencing projects on fungi...
Genome-wide maps of chromatin state in pluripotent and lineage-committed cellsTarjei S Mikkelsen
Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
Nature 448:553-60. 2007..This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations...
Assembly of polymorphic genomes: algorithms and application to Ciona savignyiJade P Vinson
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141 2023, USA
Genome Res 15:1127-35. 2005..Our method represented loci in a single copy more reliably and achieved greater contiguity than a conventional whole-genome assembly method...
Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegansJ Graham Ruby
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Cell 127:1193-207. 2006..The motif is conserved in other nematodes, presumably because of its importance for producing these diverse, autonomously expressed, small RNAs (dasRNAs)...
The genome of M. acetivorans reveals extensive metabolic and physiological diversityJames E Galagan
Whitehead Institute Center for Genome Research, Cambridge, Massachusetts 02141, USA
Genome Res 12:532-42. 2002..acetivorans a powerful model organism for the study of archaeal biology. [Sequence, data, annotations and analyses are available at http://www-genome.wi.mit.edu/.]..
The complete genome and proteome of Mycoplasma mobileJacob D Jaffe
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Genome Res 14:1447-61. 2004..The results of these analyses leave open the possibility that gliding motility might have arisen independently more than once in the mycoplasma lineage...
Initial sequencing and comparative analysis of the mouse genomeRobert H Waterston
Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
Nature 420:520-62. 2002....
Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotypeOlivier Jaillon
UMR 8030 Genoscope, , , 91057 Evry Cedex, France
Nature 431:946-57. 2004....
Human chromosome 11 DNA sequence and analysis including novel gene identificationTodd D Taylor
RIKEN Genomic Sciences Center, 1 7 22 Suehiro cho, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
Nature 440:497-500. 2006..5 million base pairs representing 99.8% coverage of the euchromatic sequence--provide scientists with a solid foundation for understanding the genetic basis of these disorders and other biological phenomena...
The genome sequence of the rice blast fungus Magnaporthe griseaRalph A Dean
Center for Integrated Fungal Research, North Carolina State University, Raleigh, North Carolina 27695, USA
Nature 434:980-6. 2005..The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation...
Uneven chromosome contraction and expansion in the maize genomeRemy Bruggmann
Munich Information Center for Protein Sequences MIPS, Institute for Bioinformatics, GSF Research Center for Environment and Health, D 85764 Neuherberg, Germany
Genome Res 16:1241-51. 2006..In addition, no differences in methylation of single genes and tandemly repeated gene copies have been detected. These results, therefore, provide new insights into the diploidization of polyploid species...
Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydisJörg Kämper
Department of Organismic Interactions, Max Planck Institute for Terrestrial Microbiology, Karl von Frisch Strasse, D 35043 Marburg, Germany
Nature 444:97-101. 2006..Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens...
Genome sequence of Aedes aegypti, a major arbovirus vectorVishvanath Nene
Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA
Science 316:1718-23. 2007..An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species...
Structure and architecture of the maize genomeGeorg Haberer
Munich Information Center for Protein Sequences, Institute for Bioinformatics, , D-85764 Neuherberg, Germany
Plant Physiol 139:1612-24. 2005..Our results indicate that much of the increase in genome size of maize relative to rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana) is attributable to an increase in number of both repetitive elements and genes...
The breakpoint region of the most common isochromosome, i(17q), in human neoplasia is characterized by a complex genomic architecture with large, palindromic, low-copy repeatsAikaterini Barbouti
Department of Clinical Genetics, Lund University Hospital, Lund, Sweden
Am J Hum Genet 74:1-10. 2004....
Mapping of Myxococcus xanthus social motility dsp mutations to the dif genesHope Lancero
Molecular Biology Institute and School of Dentistry, University of California Los Angeles, Los Angeles, CA 90095 1668, USA
J Bacteriol 184:1462-5. 2002..Another dsp allele contains a mutation in the sglK gene. About 36.6 kb around the dsp-dif locus was sequenced and annotated, and 50% of the genes are novel...
Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elementsJosee Dostie
Program in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605 0103, USA
Genome Res 16:1299-309. 2006..5C should be widely applicable for large-scale mapping of cis- and trans- interaction networks of genomic elements and for the study of higher-order chromosome structure...
