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1. Sequencing of Culex quinquefasciatus Establishes a Platform for Mosquito Comparative Genomics

Author

Arensburger, Peter, Megy, Karine, Waterhouse, Robert M., Abrudan, Jenica, Amedeo, Paolo, Antelo, Beatriz, Bartholomay, Lyric, Bidwell, Shelby, Caler, Elisabet, Camara, Francisco, Campbell, Corey L., Campbell, Kathryn S., Casola, Claudio, Castro, Marta T., Chandramouliswaran, Ishwar, Chapman, Sinéad B., Christley, Scott, Costas, Javier, Eisenstadt, Eric, Feschotte, Cedric, Fraser-Liggett, Claire, Guigo, Roderic, Haas, Brian, Hammond, Martin, Hansson, Bill S., Hemingway, Janet, Hill, Sharon R., Howarth, Clint, Ignell, Rickard, Kennedy, Ryan C., Kodira, Chinnappa D., Lobo, Neil F., Mao, Chunhong, Mayhew, George, Michel, Kristin, Mori, Akio, Liu, Nannan, Naveira, Horado, Nene, Vishvanath, Nguyen, Nam, Pearson, Matthew D., Pritham, Ellen J., Puiu, Daniela, Qi, Yumin, Ranson, Hilary, Ribeiro, Jose M. C., Roberston, Hugh M., Severson, David W., Shumway, Martin, Stanke, Mario, Strausberg, Robert L., Sun, Cheng, Sutton, Granger, Tubio, Jose Manuel C., Unger, Maria F., Vanlandingham, Dana L., Vilella, Albert J., White, Owen, White, Jared R., Wondji, Charles S., Wortman, Jennifer, Zdobnov, Evgeny M., Birren, Bruce, Christensen, Bruce M., Collins, Frank H., Cornel, Anthony, Dimopoulos, George, Hannick, Linda I., Higgs, Stephen, Lanzaro, Gregory C., Lawson, Daniel, Lee, Norman H., Muskavitch, Marc A. T., Raikhel, Alexander S., and Atkinson, Peter W.

Published
2010

2. Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa

Author

Cohen, Keira A., primary, Abeel, Thomas, additional, McGuire, Abigail Manson, additional, Desjardins, Christopher A., additional, Munsamy, Vanisha, additional, Shea, Terrance P., additional, Walker, Bruce J., additional, Bantubani, Nonkqubela, additional, Almeida, Deepak V., additional, Alvarado, Lucia, additional, Chapman, Sinead, additional, Mvelase, Nomonde R., additional, Duffy, Eamon Y., additional, Fitzgerald, Michael G., additional, Govender, Pamla, additional, Gujja, Sharvari, additional, Hamilton, Susanna, additional, Howarth, Clint, additional, Larimer, Jeffrey D., additional, Maharaj, Kasmheel, additional, Pearson, Matthew D., additional, Priest, Margaret E., additional, Zeng, Qiandong, additional, Padayatchi, Nesri, additional, Grosset, Jacques, additional, Young, Sarah K., additional, Wortman, Jennifer, additional, Mlisana, Koleka P., additional, O’Donnell, Max R., additional, Birren, Bruce W., additional, Bishai, William R., additional, Pym, Alexander S., additional, and Earl, Ashlee M., additional

Published
2015
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3. Comparative genomic characterization of Francisella tularensis strains belonging to low and high virulence subspecies

Author

Champion, Mia D, Zeng, Qiandong, Nix, Eli B, Nano, Francis E, Keim, Paul, Kodira, Chinnappa D, Borowsky, Mark, Young, Sarah, Koehrsen, Michael, Engels, Reinhard, Pearson, Matthew, Howarth, Clint, Larson, Lisa, White, Jared, Alvarado, Lucia, Forsman, Mats, Bearden, Scott W, Sjöstedt, Anders, Titball, Richard, Michell, Stephen L, Birren, Bruce, Galagan, James, Champion, Mia D, Zeng, Qiandong, Nix, Eli B, Nano, Francis E, Keim, Paul, Kodira, Chinnappa D, Borowsky, Mark, Young, Sarah, Koehrsen, Michael, Engels, Reinhard, Pearson, Matthew, Howarth, Clint, Larson, Lisa, White, Jared, Alvarado, Lucia, Forsman, Mats, Bearden, Scott W, Sjöstedt, Anders, Titball, Richard, Michell, Stephen L, Birren, Bruce, and Galagan, James

Abstract

Tularemia is a geographically widespread, severely debilitating, and occasionally lethal disease in humans. It is caused by infection by a gram-negative bacterium, Francisella tularensis. In order to better understand its potency as an etiological agent as well as its potential as a biological weapon, we have completed draft assemblies and report the first complete genomic characterization of five strains belonging to the following different Francisella subspecies (subsp.): the F. tularensis subsp. tularensis FSC033, F. tularensis subsp. holarctica FSC257 and FSC022, and F. tularensis subsp. novicida GA99-3548 and GA99-3549 strains. Here, we report the sequencing of these strains and comparative genomic analysis with recently available public Francisella sequences, including the rare F. tularensis subsp. mediasiatica FSC147 strain isolate from the Central Asian Region. We report evidence for the occurrence of large-scale rearrangement events in strains of the holarctica subspecies, supporting previous proposals that further phylogenetic subdivisions of the Type B clade are likely. We also find a significant enrichment of disrupted or absent ORFs proximal to predicted breakpoints in the FSC022 strain, including a genetic component of the Type I restriction-modification defense system. Many of the pseudogenes identified are also disrupted in the closely related rarely human pathogenic F. tularensis subsp. mediasiatica FSC147 strain, including modulator of drug activity B (mdaB) (FTT0961), which encodes a known NADPH quinone reductase involved in oxidative stress resistance. We have also identified genes exhibiting sequence similarity to effectors of the Type III (T3SS) and components of the Type IV secretion systems (T4SS). One of the genes, msrA2 (FTT1797c), is disrupted in F. tularensis subsp. mediasiatica and has recently been shown to mediate bacterial pathogen survival in host organisms. Our findings suggest that in addition to the duplication of the Francisella

Published
2009
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4. Comparative Genomic Characterization of Francisella tularensis Strains Belonging to Low and High Virulence Subspecies

Author

Champion, Mia D., primary, Zeng, Qiandong, additional, Nix, Eli B., additional, Nano, Francis E., additional, Keim, Paul, additional, Kodira, Chinnappa D., additional, Borowsky, Mark, additional, Young, Sarah, additional, Koehrsen, Michael, additional, Engels, Reinhard, additional, Pearson, Matthew, additional, Howarth, Clint, additional, Larson, Lisa, additional, White, Jared, additional, Alvarado, Lucia, additional, Forsman, Mats, additional, Bearden, Scott W., additional, Sjöstedt, Anders, additional, Titball, Richard, additional, Michell, Stephen L., additional, Birren, Bruce, additional, and Galagan, James, additional

Published
2009
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5. Coefficients.

Author

Howarth, Clint

Abstract

Presents the short story "Coefficients," by Clint Howarth.

Published
2005

6. Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosisfrom KwaZulu-Natal, South Africa

Author

Cohen, Keira A., Abeel, Thomas, McGuire, Abigail Manson, Desjardins, Christopher A., Munsamy, Vanisha, Shea, Terrance P., Walker, Bruce J., Bantubani, Nonkqubela, Almeida, Deepak V., Alvarado, Lucia, Chapman, Sinead, Mvelase, Nomonde R., Duffy, Eamon Y., Fitzgerald, Michael G., Govender, Pamla, Gujja, Sharvari, Hamilton, Susanna, Howarth, Clint, Larimer, Jeffrey D., Maharaj, Kasmheel, Pearson, Matthew D., Priest, Margaret E., Zeng, Qiandong, Padayatchi, Nesri, Grosset, Jacques, Young, Sarah K., Wortman, Jennifer, Mlisana, Koleka P., O’Donnell, Max R., Birren, Bruce W., Bishai, William R., Pym, Alexander S., and Earl, Ashlee M.

Abstract

The largest global outbreak of extensively drug-resistant (XDR) tuberculosis (TB) was identified in Tugela Ferry, KwaZulu-Natal (KZN), South Africa in 2005. The antecedents and timing of the emergence of drug resistance in this fatal epidemic XDR outbreak are unknown, and it is unclear whether drug resistance in this region continues to be driven by clonal spread or by the development of de novoresistance. A whole genome sequencing and drug susceptibility testing (DST) was performed on 337 clinical isolates of Mycobacterium tuberculosis(M.tb) collected in KZN from 2008 to 2013, in addition to three historical isolates, one of which was isolated during the Tugela Ferry outbreak. Using a variety of whole genome comparative approaches, 11 drug-resistant clones of M.tbcirculating from 2008 to 2013 were identified, including a 50-member clone of XDR M.tbthat was highly related to the Tugela Ferry XDR outbreak strain. It was calculated that the evolutionary trajectory from first-line drug resistance to XDR in this clone spanned more than four decades and began at the start of the antibiotic era. It was also observed that frequent de novoevolution of MDR and XDR was present, with 56 and 9 independent evolutions, respectively. Thus, ongoing amplification of drug-resistance in KwaZulu-Natal is driven by both clonal spread and de novoacquisition of resistance. In drug-resistant TB, isoniazid resistance was overwhelmingly the initial resistance mutation to be acquired, which would not be detected by current rapid molecular diagnostics that assess only rifampicin resistance.

Published
2015
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7. A catalog of reference genomes from the human microbiome.

Author

Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, Wortman JR, Rusch DB, Mitreva M, Sodergren E, Chinwalla AT, Feldgarden M, Gevers D, Haas BJ, Madupu R, Ward DV, Birren BW, Gibbs RA, Methe B, Petrosino JF, Strausberg RL, Sutton GG, White OR, Wilson RK, Durkin S, Giglio MG, Gujja S, Howarth C, Kodira CD, Kyrpides N, Mehta T, Muzny DM, Pearson M, Pepin K, Pati A, Qin X, Yandava C, Zeng Q, Zhang L, Berlin AM, Chen L, Hepburn TA, Johnson J, McCorrison J, Miller J, Minx P, Nusbaum C, Russ C, Sykes SM, Tomlinson CM, Young S, Warren WC, Badger J, Crabtree J, Markowitz VM, Orvis J, Cree A, Ferriera S, Fulton LL, Fulton RS, Gillis M, Hemphill LD, Joshi V, Kovar C, Torralba M, Wetterstrand KA, Abouellleil A, Wollam AM, Buhay CJ, Ding Y, Dugan S, FitzGerald MG, Holder M, Hostetler J, Clifton SW, Allen-Vercoe E, Earl AM, Farmer CN, Liolios K, Surette MG, Xu Q, Pohl C, Wilczek-Boney K, and Zhu D

Subjects
Bacteria classification, Bacteria genetics, Bacterial Proteins chemistry, Bacterial Proteins genetics, Biodiversity, Computational Biology, Databases, Genetic, Gastrointestinal Tract microbiology, Genes, Bacterial, Genetic Variation, Genome, Archaeal, Humans, Metagenomics methods, Metagenomics standards, Mouth microbiology, Peptides chemistry, Peptides genetics, Phylogeny, Respiratory System microbiology, Skin microbiology, Urogenital System microbiology, Genome, Bacterial, Metagenome genetics, Sequence Analysis, DNA standards
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.

Published
2010
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