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.

Staphylococcal Enterotoxin P Predicts Bacteremia in Hospitalized Patients Colonized With Methicillin-Resistant Staphylococcus aureus

Abstract: (See the editorial commentary by Stevenson and Wang on pages 488–90.) Staphylococcus aureus is a major cause of healthcare-associated infections [1], and patients are often colonized with this bacterium before developing invasive disease [2, 3]. Increasing carriage of methicillin-resistant S. aureus (MRSA), an antibiotic-resistant strain, has resulted in a doubling of MRSA-related hospitalizations, including up to 56 000 US hospitalizations per year for MRSA bacteremia [4–6]. Overall, nearly 19 000 patients die annually in US hospitals from MRSA infections [7]. MRSA carriage in the United States is at least 7% in general hospital populations [8] and as high as 24% in intensive care units (ICUs) [9]. The risk of MRSA infection in the year following colonization is as high as 33%, with 18% being primary bloodstream infections [10]. Nasal carriers of MRSA versus methicillin-susceptible S. aureus (MSSA) have a 4 times higher incidence of bacteremia, with >80% of cases involving an identical strain in the nares and the blood [3, 11, 12]. In addition, the mortality for bacteremia is 2 times higher with MRSA as compared to MSSA [13]. Both host and pathogen factors play a role in the development of MRSA infections. Host factors include prolonged hospitalization [14–17], advanced age [10, 14], intravenous catheterization [15, 17–19], mechanical ventilation [18, 20, 21], antibiotic exposure [17, 21], soft-tissue wounds [15, 19], and chronic diseases, such as diabetes, renal insufficiency, cancer, and malnutrition [10, 18, 22]. Pathogen factors predicting MRSA bacteremia are the subject of ongoing debate [23]. Studies accounting for epidemiologic factors of the host in addition to genetic variation in different MRSA strains are lacking. We therefore sought to look at combined host and pathogen factors in a prospective cohort.

Correction: Disruption of the nuclear hormone receptor RORα in staggerer mice

Abstract: Nature 379, 736-739 (1996) THE labelling of Fig. 3a and b is incorrect: rostral is to the upper left and the fourth ventricle is seen as a triangular space above and to the right of the cerebellum. The RORotl cDNA sequence has been submitted to GenBank, accession number U53228.

Populations of latent Mycobacterium tuberculosis lack a cell wall: Isolation, visualization, and whole-genome characterization

Abstract: Objective/Background Mycobacterium tuberculosis (MTB) causes active tuberculosis (TB) in only a small percentage of infected people. In most cases, the infection is clinically latent, where bacilli can persist in human hosts for years without causing disease. Surprisingly, the biology of such persister cells is largely unknown. This study describes the isolation, identification, and whole-genome sequencing (WGS) of latent TB bacilli after 782 days (26 months) of latency (the ability of MTB bacilli to lie persistent). Methods The in vitro double-stress model of latency (oxygen and nutrition) was designed for MTB culture. After 26 months of latency, MTB cells that persisted were isolated and investigated under light and atomic force microscopy. Spoligotyping and WGS were performed to verify the identity of the strain. Results We established a culture medium in which MTB bacilli arrest their growth, reduce their size (0.3–0.1 μm), lose their acid fastness (85–90%) and change their shape. Spoligopatterns of latent cells were identical to original H 37 R v , with differences observed at spacers two and 14. WGS revealed only a few genetic changes relative to the already published H 37 R v reference genome. Among these was a large 2064-bp insertion (RvD6), which was originally detected in both H 37 R a and CDC1551, but not H 37 R v . Conclusion Here, we show cell-wall free cells of MTB bacilli in their latent state, and the biological adaptation of these cells was more phenotypic in nature than genomic. These cell-wall free cells represent a good model for understanding the nature of TB latency.

Extensive global movement of multidrug-resistant M. tuberculosis strains revealed by whole-genome analysis

Abstract: Background: While the international spread of multidrug-resistant (MDR) Mycobacterium tuberculosis strains is an acknowledged public health threat, a broad and more comprehensive examination of the global spread of MDR-tuberculosis (TB) using whole-genome sequencing has not yet been performed. Methods: In a global dataset of 5310 M. tuberculosis whole-genome sequences isolated from five continents, we performed a phylogenetic analysis to identify and characterise clades of MDR-TB with respect to geographic dispersion. Results: Extensive international dissemination of MDR-TB was observed, with identification of 32 migrant MDR-TB clades with descendants isolated in 17 unique countries. Relatively recent movement of strains from both Beijing and non-Beijing lineages indicated successful global spread of varied genetic backgrounds. Migrant MDR-TB clade members shared relatively recent common ancestry, with a median estimate of divergence of 13-27 years. Migrant extensively drug-resistant (XDR)-TB clades were not observed, although development of XDR-TB within migratory MDR-TB clades was common. Conclusions: Application of genomic techniques to investigate global MDR migration patterns revealed extensive global spread of MDR clades between countries of varying TB burden. Further expansion of genomic studies to incorporate isolates from diverse global settings into a single analysis, as well as data sharing platforms that facilitate genomic data sharing across country lines, may allow for future epidemiological analyses to monitor for international transmission of MDR-TB. In addition, efforts to perform routine whole-genome sequencing on all newly identified M. tuberculosis, like in England, will serve to better our understanding of the transmission dynamics of MDR-TB globally.

Draft Genome Sequence of the Cellulolytic Fungus Chaetomium globosum.

Abstract: Chaetomium globosum is a filamentous fungus typically isolated from cellulosic substrates. This species also causes superficial infections of humans and, more rarely, can cause cerebral infections. ...

Initial sequencing and analysis of the human genome.

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.

The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data

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.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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。

SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing

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.

Full-length transcriptome assembly from RNA-Seq data without a reference genome.

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.