Jessica B. Hostetler

Bio: Jessica B. Hostetler is an academic researcher from Wellcome Trust Sanger Institute. The author has contributed to research in topics: Genome & Gene. The author has an hindex of 21, co-authored 29 publications receiving 5197 citations. Previous affiliations of Jessica B. Hostetler include J. Craig Venter Institute & TigerLogic.

The Genome of the African Trypanosome Trypanosoma brucei

Abstract: African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ∼900 pseudogenes and ∼1700 T. brucei–specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.

A Catalog of Reference Genomes from the Human Microbiome

Abstract: The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97%) were unique. In addition, this set of microbial genomes allows for approximately 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented.

Comparative Genomics of Plant-Associated Pseudomonas spp.: Insights into Diversity and Inheritance of Traits Involved in Multitrophic Interactions

Abstract: We provide here a comparative genome analysis of ten strains within the Pseudomonas fluorescens group including seven new genomic sequences. These strains exhibit a diverse spectrum of traits involved in biological control and other multitrophic interactions with plants, microbes, and insects. Multilocus sequence analysis placed the strains in three sub-clades, which was reinforced by high levels of synteny, size of core genomes, and relatedness of orthologous genes between strains within a sub-clade. The heterogeneity of the P. fluorescens group was reflected in the large size of its pan-genome, which makes up approximately 54% of the pan-genome of the genus as a whole, and a core genome representing only 45–52% of the genome of any individual strain. We discovered genes for traits that were not known previously in the strains, including genes for the biosynthesis of the siderophores achromobactin and pseudomonine and the antibiotic 2-hexyl-5-propyl-alkylresorcinol; novel bacteriocins; type II, III, and VI secretion systems; and insect toxins. Certain gene clusters, such as those for two type III secretion systems, are present only in specific sub-clades, suggesting vertical inheritance. Almost all of the genes associated with multitrophic interactions map to genomic regions present in only a subset of the strains or unique to a specific strain. To explore the evolutionary origin of these genes, we mapped their distributions relative to the locations of mobile genetic elements and repetitive extragenic palindromic (REP) elements in each genome. The mobile genetic elements and many strain-specific genes fall into regions devoid of REP elements (i.e., REP deserts) and regions displaying atypical tri-nucleotide composition, possibly indicating relatively recent acquisition of these loci. Collectively, the results of this study highlight the enormous heterogeneity of the P. fluorescens group and the importance of the variable genome in tailoring individual strains to their specific lifestyles and functional repertoire.

Genome Project Standards in a New Era of Sequencing

Abstract: A Joint Announcement on Genome Sequence Standards Genome project standards in a new era of sequencing P. S. G. Chain 1,2,3,4,22,* , D. V. Grafham 5,* , R. S. Fulton 6 , M. G. FitzGerald 7 , J. Hostetler 8 , D. Muzny 9 , J. C. Detter 1,10 , J. Ali 11 , B.Birren 7 , D. C. Bruce 1, 10 , C. Buhay 9 , J. R. Cole 3,4 , Y. Ding 9 , S. Dugan 9 , D. Field 12 , G. M. Garrity 3,4 , R. Gibbs 9 , T. Graves 6 , C. S. Han 1, 10 , S. H. Harrison 3 , S. Highlander 9 , P. Hugenholtz 1 , H. M. Khouri 13 , C. D. Kodira 7,23 , E. Kolker 14,15 , N. C. Kyrpides 1 , D. Lang 1,2 , A. Lapidus 1 , S. A. Malfatti 1,2 , V. Markowitz 16 , T. Metha 7 , K. E. Nelson 8 , J. Parkhill 5 , S. Pitluck 1 , X. Qin 9 , T. D. Read 17 , J. Schmutz 18 , S. Sozhamannan 19 , R. Strausberg 8 , G. Sutton 8 , N. R. Thomson 5 , J. M. Tiedje 3,4 , G. Weinstock 6 , A. Wollam 6 , and the entire GSC 20 and HMP Jumpstart 21 consortia. U.S. Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California 94550, USA Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA Center for Microbial Ecology, Michigan State University, East Lansing, Michigan 48824, USA The Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom The Genome Center, Washington University School of Medicine, St Louis, Missouri 63108, USA The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02141, USA J. Craig Venter Institute, Rockville, Maryland 20850, USA Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada Natural Environmental Research Council Centre for Ecology and Hydrology, Oxford, Oxfordshire OX1 3SR, UK National Center for Biotechnology Information, National Library of Medicine, Rockville, Maryland 20850, USA Seattle Children’s Hospital and Research Institute, Seattle, Washington 98101, USA Biomedical & Health Informatics Division, MEBI, University of Washington School of Medicine, Seattle, Washington 98195, USA Biological Data Management and Technology Center, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA Emory GRA Genomics Core, Emory University School of Medicine, Atlanta, Georgia 30322, USA HudsonAlpha Genome Sequencing Center, HudsonAlpha Institute, Huntsville, Alabama 35806, USA Biological Defense Research Directorate, Naval Medical Research Center, Silver Spring, Maryland 20910, USA Genomic Standards Consortium Human Microbiome Project Jumpstart Consortium Current address: Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA Current address: 454 Life Sciences, Branford, Connecticut 06405, USA *Address correspondence to Patrick Chain (pchain@lanl.gov) and Darren Grafham (dg1@sanger.ac.uk)

Genome Project Standards in a New Era of Sequencing

Abstract: For over a decade, genome sequences have adhered to only two standards that are relied on for purposes of sequence analysis by interested third parties (1, 2). However, ongoing developments in revolutionary sequencing technologies have resulted in a redefinition of traditional whole-genome sequencing that requires reevaluation of such standards. With commercially available 454 pyrosequencing (followed by Illumina, SOLiD, and now Helicos), there has been an explosion of genomes sequenced under the moniker “draft”; however, these can be very poor quality genomes (due to inherent errors in the sequencing technologies, and the inability of assembly programs to fully address these errors). Further, one can only infer that such draft genomes may be of poor quality by navigating through the databases to find the number and type of reads deposited in sequence trace repositories (and not all genomes have this available), or to identify the number of contigs or genome fragments deposited to the database. The difficulty in assessing the quality of such deposited genomes has created some havoc for genome analysis pipelines and has contributed to many wasted hours. Exponential leaps in raw sequencing capability and greatly reduced prices have further skewed the time- and cost-ratios of draft data generation versus the painstaking process of improving and finishing a genome. The result is an ever-widening gap between drafted and finished genomes that only promises to continue (see the figure, page 236); hence, there is an urgent need to distinguish good from poor data sets.

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。

Diet rapidly and reproducibly alters the human gut microbiome

Abstract: Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes

Abstract: Large-scale recovery of genomes from isolates, single cells, and metagenomic data has been made possible by advances in computational methods and substantial reductions in sequencing costs. Although this increasing breadth of draft genomes is providing key information regarding the evolutionary and functional diversity of microbial life, it has become impractical to finish all available reference genomes. Making robust biological inferences from draft genomes requires accurate estimates of their completeness and contamination. Current methods for assessing genome quality are ad hoc and generally make use of a limited number of “marker” genes conserved across all bacterial or archaeal genomes. Here we introduce CheckM, an automated method for assessing the quality of a genome using a broader set of marker genes specific to the position of a genome within a reference genome tree and information about the collocation of these genes. We demonstrate the effectiveness of CheckM using synthetic data and a wide range of isolate-, single-cell-, and metagenome-derived genomes. CheckM is shown to provide accurate estimates of genome completeness and contamination and to outperform existing approaches. Using CheckM, we identify a diverse range of errors currently impacting publicly available isolate genomes and demonstrate that genomes obtained from single cells and metagenomic data vary substantially in quality. In order to facilitate the use of draft genomes, we propose an objective measure of genome quality that can be used to select genomes suitable for specific gene- and genome-centric analyses of microbial communities.

Enterotypes of the human gut microbiome

Abstract: Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.