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.

Endurance, refuge, and reemergence of dengue virus type 2, Puerto Rico, 1986-2007.

Abstract: Epidemic dengue fever (DF) and the emergence of dengue hemorrhagic fever (DHF) in the Americas are associated with increased endemicity and cocirculation of the 4 dengue virus (DENV) serotypes, 1–4 (1). These increases have been particularly evident in Puerto Rico, where transmission increased during the past 25 years (2–4). The first DHF epidemics in the Americas occurred in the 1980s and were caused by the Asian/American genotype of DENV-2, then new to the region, which rapidly replaced the American genotype (5–7). This replacement has been linked to a potential to cause higher viremia and severe illness (8–10). Introduction of DENV-3 in the mid 1990s and increased human population and travel further fostered larger and more frequent DF and DHF epidemics in the region (11–13). Although all 4 DENV serotypes circulate on the island, DENV-2 circulated continuously for 25 years. Previously, a partial sequence analysis from 74 DENV-2 isolates collected in Puerto Rico during 7 years throughout a 14-year period (1987–2001) showed a DENV-2 lineage evolving through a series of turnover events (14). A lineage replacement in 1994 appeared to be associated with a foreign virus but only 3 other reintroductions were found, all linked to the 1998 epidemic, the largest in Puerto Rico history (14). This was a turning point in the epidemiology of dengue, with DENV-2 (and DENV-1 and -4) rapidly declining during the expansion of DENV-3. However, transmission of DENV-2 persisted at low levels during 1999–2003 and increased thereafter. This serotype turnover offers new opportunities to study the evolution of DENV-2. Our analysis illustrates the genetic composition and population diversity of DENV-2 throughout 22 consecutive years of sampling in Puerto Rico and may explain the evolutionary resilience and long-term establishment of this virus.

Mouse Molecular Cytogenetic Resource: 157 BACs Link the Chromosomal and Genetic Maps

Abstract: The achievements of the human and mouse genome projects provide increasing numbers of genes and phenotype-associated mutations (DeBry and Seldin 1996; Schuler et al. 1996). Linking the normal and mutant forms of the genes with their functions remains one of biology’s great challenges. To do this the DNA sequence must be defined ultimately with respect to the chromosomal location of the genes, a task that is facilitated by the many disease models available for study in the mouse. Although the genetic map of the mouse provides a powerful tool to link mutations and diseases with the genes (Dietrich et al. 1996), cytogenetic analysis is essential to define genes associated with chromosomal rearrangements. Molecular cytogenetic analysis, which has been exploited widely for localizing cloned genes, genomic sequences, and disease-related chromosomal rearrangements in the human, has not proven as useful in murine genetics. Whereas human genes and breakpoints can be rapidly and accurately mapped cytogenetically (X.-N. Chen, S. Mitchell, Z.-G. Sun, D. Noya, S. Ma, G.S. Sekhon, K. Thompson, W.T. Hsu, P. Wong, N. Wang et al., unpubl.), the common morphology and less distinct landmarks of mouse chromosomes have combined with the lack of molecular cytogenetic markers to hamper similar analyses in the mouse. To bridge the gap between molecular and cytological methods, previous studies have developed a number of reagents for mouse chromosome identification. These include whole-chromosome reagents (Breneman et al. 1993; Weier et al. 1994; Rabbitts et al. 1995; Liyanage et al. 1996; Xiao et al. 1996) and cosmid or P1 clones used with repeat-sequence-based alternatives to dye-based banding techniques (Boyle et al. 1990). Additionally, mouse yeast artificial chromosome (YAC) and P1 clones have been used to generate chromosome-specific probes through FISH and DAPI counterstaining (Mongelard et al. 1996; Shi et al. 1997). This report combines the products of the mouse genome project with molecular cytogenetic techniques to generate a new set of reagents, bacterial artificial chromosome (BAC) clones with a subset linked to centromeric and telomeric genetic markers. These serve to identify mouse chromosomes 1–19 and X, to fluorescently tag the ends of their genetic maps, and to define multiple band landmarks on each chromosome with unique BACs. The stability of BAC clones, the ease of BAC DNA purification, and the strong fluorescence in situ hybridization (FISH) signals resulting from the large insert size, make them superior molecular cytogenetic reagents (Korenberg and Chen 1995; X-.N. Chen, S. Mitchell, Z.-G. Sun, D. Noya, S. Ma, G.S. Sekhon, K. Thompson, W.T. Hsu, P. Wong, N. Wang et al., unpubl.). By including BAC clones that span each chromosome and contain markers from the ends of the genetic maps, the collection serves to integrate cytogenetic, genetic, and physical maps. The availability of such probes extends mouse analysis to interphase, and facilitates the rapid definition of chromosomal rearrangements and their associated candidate genes.

Fluid Spatial Dynamics of West Nile Virus in the United States: Rapid Spread in a Permissive Host Environment

Abstract: The introduction of West Nile virus (WNV) into North America in 1999 is a classic example of viral emergence in a new environment, with its subsequent dispersion across the continent having a major impact on local bird populations. Despite the importance of this epizootic, the pattern, dynamics, and determinants of WNV spread in its natural hosts remain uncertain. In particular, it is unclear whether the virus encountered major barriers to transmission, or spread in an unconstrained manner, and if specific viral lineages were favored over others indicative of intrinsic differences in fitness. To address these key questions in WNV evolution and ecology, we sequenced the complete genomes of approximately 300 avian isolates sampled across the United States between 2001 and 2012. Phylogenetic analysis revealed a relatively star-like tree structure, indicative of explosive viral spread in the United States, although with some replacement of viral genotypes through time. These data are striking in that viral sequences exhibit relatively limited clustering according to geographic region, particularly for those viruses sampled from birds, and no strong phylogenetic association with well-sampled avian species. The genome sequence data analyzed here also contain relatively little evidence for adaptive evolution, particularly of structural proteins, suggesting that most viral lineages are of similar fitness and that WNV is well adapted to the ecology of mosquito vectors and diverse avian hosts in the United States. In sum, the molecular evolution of WNV in North America depicts a largely unfettered expansion within a permissive host and geographic population with little evidence of major adaptive barriers. IMPORTANCE How viruses spread in new host and geographic environments is central to understanding the emergence and evolution of novel infectious diseases and for predicting their likely impact. The emergence of the vector-borne West Nile virus (WNV) in North America in 1999 represents a classic example of this process. Using approximately 300 new viral genomes sampled from wild birds, we show that WNV experienced an explosive spread with little geographical or host constraints within birds and relatively low levels of adaptive evolution. From its introduction into the state of New York, WNV spread across the United States, reaching California and Florida within 4 years, a migration that is clearly reflected in our genomic sequence data, and with a general absence of distinct geographical clusters of bird viruses. However, some geographically distinct viral lineages were found to circulate in mosquitoes, likely reflecting their limited long-distance movement compared to avian species.

Mobile genes in the human microbiome are structured from global to individual scales

Abstract: Recent work has underscored the importance of the microbiome in human health, and has largely attributed differences in phenotype to differences in the species present among individuals. However, mobile genes can confer profoundly different phenotypes on different strains of the same species. Little is known about the function and distribution of mobile genes in the human microbiome, and in particular whether the gene pool is globally homogenous or constrained by human population structure. Here, we investigate this question by comparing the mobile genes found in the microbiomes of 81 metropolitan North Americans with those of 172 agrarian Fiji islanders using a combination of single-cell genomics and metagenomics. We find large differences in mobile gene content between the Fijian and North American microbiomes, with functional variation that mirrors known dietary differences such as the excess of plant-based starch degradation genes found in Fijian individuals. Notably, we also observed differences between the mobile gene pools of neighbouring Fijian villages, even though microbiome composition across villages is similar. Finally, we observe high rates of recombination leading to individual-specific mobile elements, suggesting that the abundance of some genes may reflect environmental selection rather than dispersal limitation. Together, these data support the hypothesis that human activities and behaviours provide selective pressures that shape mobile gene pools, and that acquisition of mobile genes is important for colonizing specific human populations.

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.