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Bruce W. Birren

Bio: Bruce W. Birren is an academic researcher from Broad Institute. The author has contributed to research in topics: Genome & Gene. The author has an hindex of 103, co-authored 205 publications receiving 113491 citations. Previous affiliations of Bruce W. Birren include Massachusetts Institute of Technology & California Institute of Technology.
Topics: Genome, Gene, Genomics, Population, Human genome


Papers
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Journal ArticleDOI
TL;DR: The BACs are shown how they provide molecular links for understanding human genomic duplications, meiosis, and evolution, as well as reagents for conducting genome-wide prenatal diagnosis at the molecular level and for detecting gene candidates associated with novel cancer breakpoints.
Abstract: Translating problems of human disease into the language of the human genome requires a unified resource that bridges DNA sequence through chromosome bands. Such a resource must link the three types of linear arrays that represent the human genome: database arrays (genetic and physical maps and ultimately DNA sequence), chromosome bands visible in single cells, and ordered clone arrays. Genome maps have been previously either STS-based, with marker order obtained using a combination of STS-content of large insert yeast artificial chromosome (YAC) clones, radiation hybrid (RH) mapping, and genetic mapping (Hudson et al. 1995; Deloukas et al. 1998), or BAC-based, with order obtained at 2–6 Mb through high resolution mapping by fluorescence in situ hybridization (FISH) with respect to human chromosome landmarks (Korenberg et al. 1992). During the course of these efforts, a strategy to integrate these maps was established. BACs are well suited for a permanent FISH-mapped and integrated clone resource in that they represent a stable and easily manipulated form of cloned DNA and produce bright, well defined signals on metaphase and interphase chromosome preparations (Korenberg and Chen 1995). We now report the construction of a genome-wide array of bacterial artificial chromosomes (BACs) that is integrated with the cytogenetic, genetic, and STS maps and characterized for homology to the remainder of the human genome by FISH.

65 citations

Book ChapterDOI
TL;DR: Both examples of findings from comparative analysis of fungal sequences are discussed, with a specific emphasis on yeast genomes, and on the analytical approaches taken to mine fungal genomes.
Abstract: The sequence of Saccharomyces cerevisiae enabled systematic genome-wide experimental approaches, demonstrating the power of having the complete genome of an organism The rapid impact of these methods on research in yeast mobilized an effort to expand genomic resources for other fungi The “fungal genome initiative” represents an organized genome sequencing effort to promote comparative and evolutionary studies across the fungal kingdom Through such an approach, scientists can not only better understand specific organisms but also illuminate the shared and unique aspects of fungal biology that underlie the importance of fungi in biomedical research, health, food production, and industry To date, assembled genomes for over 100 fungi are available in public databases, and many more sequencing projects are underway Here, we discuss both examples of findings from comparative analysis of fungal sequences, with a specific emphasis on yeast genomes, and on the analytical approaches taken to mine fungal genomes New sequencing methods are accelerating comparative studies of fungi by reducing the cost and difficulty of sequencing This has driven more common use of sequencing applications, such as to study genome-wide variation in populations or to deeply profile RNA transcripts These and further technological innovations will continue to be piloted in yeasts and other fungi, and will expand the applications of sequencing to study fungal biology

63 citations

Journal ArticleDOI
TL;DR: Investigation of the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples taken from 17 patients infected with DENV type 1 found clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host.
Abstract: Little is known about the rate at which genetic variation is generated within intrahost populations of dengue virus (DENV) and what implications this diversity has for dengue pathogenesis, disease severity, and host immunity. Previous studies of intrahost DENV variation have used a low frequency of sampling and/or experimental methods that do not fully account for errors generated through amplification and sequencing of viral RNAs. We investigated the extent and pattern of genetic diversity in sequence data in domain III (DIII) of the envelope (E) gene in serial plasma samples (n = 49) taken from 17 patients infected with DENV type 1 (DENV-1), totaling some 8,458 clones. Statistically rigorous approaches were employed to account for artifactual variants resulting from amplification and sequencing, which we suggest have played a major role in previous studies of intrahost genetic variation. Accordingly, nucleotide sequence diversities of viral populations were very low, with conservative estimates of the average levels of genetic diversity ranging from 0 to 0.0013. Despite such sequence conservation, we observed clear evidence for mixed infection, with the presence of multiple phylogenetically distinct lineages present within the same host, while the presence of stop codon mutations in some samples suggests the action of complementation. In contrast to some previous studies we observed no relationship between the extent and pattern of DENV-1 genetic diversity and disease severity, immune status, or level of viremia.

61 citations

Journal ArticleDOI
TL;DR: This research presents a new probabilistic approach to estimating the response of the immune system to EMTs using a simple, straightforward, and scalable approach called “spot-spot analysis”.
Abstract: Nat. Biotechnol. 35, 725–731 (2017); published online 8 August 2017; corrected after print 29 November 2017; corrected after print 7 December 2017 In the version of this article initially published, the following acknowledgment was omitted: A.L. was supported by the Russian Science Foundation (grantnumber 14-50-00069).

61 citations

Journal ArticleDOI
01 Feb 2009-Genetics
TL;DR: A set of single nucleotide polymorphisms (SNPs) between the reference Neurospora crassa strain Oak Ridge and the Mauriceville strain, of sufficient density to allow fine mapping of most loci, are discovered and validated.
Abstract: We report the discovery and validation of a set of single nucleotide polymorphisms (SNPs) between the reference Neurospora crassa strain Oak Ridge and the Mauriceville strain (FGSC 2555), of sufficient density to allow fine mapping of most loci. Sequencing of Mauriceville cDNAs and alignment to the completed genomic sequence of the Oak Ridge strain identified 19,087 putative SNPs. Of these, a subset was validated by cleaved amplified polymorphic sequence (CAPS), a simple and robust PCR-based assay that reliably distinguishes between SNP alleles. Experimental confirmation resulted in the development of 250 CAPS markers distributed evenly over the genome. To demonstrate the applicability of this map, we used bulked segregant analysis followed by interval mapping to locate the csp-1 mutation to a narrow region on LGI. Subsequently, we refined mapping resolution to 74 kbp by developing additional markers, resequenced the candidate gene, NCU02713.3, in the mutant background, and phenocopied the mutation by gene replacement in the WT strain. Together, these techniques demonstrate a generally applicable and straightforward approach for the isolation of novel genes from existing mutants. Data on both putative and validated SNPs are deposited in a customized public database at the Broad Institute, which encourages augmentation by community users.

59 citations


Cited by
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Journal ArticleDOI
Eric S. Lander1, Lauren Linton1, Bruce W. Birren1, Chad Nusbaum1  +245 moreInstitutions (29)
15 Feb 2001-Nature
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

22,269 citations

Journal ArticleDOI
TL;DR: The GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.
Abstract: Next-generation DNA sequencing (NGS) projects, such as the 1000 Genomes Project, are already revolutionizing our understanding of genetic variation among individuals. However, the massive data sets generated by NGS—the 1000 Genome pilot alone includes nearly five terabases—make writing feature-rich, efficient, and robust analysis tools difficult for even computationally sophisticated individuals. Indeed, many professionals are limited in the scope and the ease with which they can answer scientific questions by the complexity of accessing and manipulating the data produced by these machines. Here, we discuss our Genome Analysis Toolkit (GATK), a structured programming framework designed to ease the development of efficient and robust analysis tools for next-generation DNA sequencers using the functional programming philosophy of MapReduce. The GATK provides a small but rich set of data access patterns that encompass the majority of analysis tool needs. Separating specific analysis calculations from common data management infrastructure enables us to optimize the GATK framework for correctness, stability, and CPU and memory efficiency and to enable distributed and shared memory parallelization. We highlight the capabilities of the GATK by describing the implementation and application of robust, scale-tolerant tools like coverage calculators and single nucleotide polymorphism (SNP) calling. We conclude that the GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.

20,557 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies.
Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V−SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online (http://bioinf.spbau.ru/spades). It is distributed as open source software.

16,859 citations

Journal ArticleDOI
TL;DR: The Trinity method for de novo assembly of full-length transcripts and evaluate it on samples from fission yeast, mouse and whitefly, whose reference genome is not yet available, providing a unified solution for transcriptome reconstruction in any sample.
Abstract: Massively parallel sequencing of cDNA has enabled deep and efficient probing of transcriptomes. Current approaches for transcript reconstruction from such data often rely on aligning reads to a reference genome, and are thus unsuitable for samples with a partial or missing reference genome. Here we present the Trinity method for de novo assembly of full-length transcripts and evaluate it on samples from fission yeast, mouse and whitefly, whose reference genome is not yet available. By efficiently constructing and analyzing sets of de Bruijn graphs, Trinity fully reconstructs a large fraction of transcripts, including alternatively spliced isoforms and transcripts from recently duplicated genes. Compared with other de novo transcriptome assemblers, Trinity recovers more full-length transcripts across a broad range of expression levels, with a sensitivity similar to methods that rely on genome alignments. Our approach provides a unified solution for transcriptome reconstruction in any sample, especially in the absence of a reference genome.

15,665 citations