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152. Molecular Detection of Minimal Residual Disease Precedes Morphological Relapse and Could be Used to Identify Relapse in Pediatric and Young Adult B-Cell Acute Lymphoblastic Leukemia Patients Treated with Tisagenlecleucel

Author

Pulsipher, Michael A., primary, Han, Xia, additional, Quigley, Máire, additional, Kari, Gabor, additional, Rives, Susana, additional, Laetsch, Theodore W., additional, Myers, Gary Douglas, additional, Hiramatsu, Hidefumi, additional, Yanik, Gregory A., additional, Qayed, Muna, additional, Driscoll, Timothy, additional, Boyer, Michael W., additional, Stefanski, Heather, additional, Büchner, Jochen, additional, Baruchel, Andre, additional, Bader, Peter, additional, Yi, Lan, additional, Kalfoglou, Creton, additional, Robins, Harlan, additional, Yusko, Erik, additional, Görgün, Güllü, additional, Bleickardt, Eric, additional, Wong, Stephane, additional, and Grupp, Stephan A., additional

Published
2018
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157. 4 Prehospital recognition and antibiotics for 999 patients with sepsis: protocol for a feasibility study

Author

Moore, Chris, primary, Bulger, Jenna, additional, Morgan, Matt, additional, Driscoll, Timothy, additional, Porter, Alison, additional, Islam, Saiful, additional, Smyth, Mike, additional, Perkins, Gavin, additional, Sewell, Bernadette, additional, Rainer, Timothy, additional, Nanayakkara, Prabath, additional, Okolie, Chukwudi, additional, Allen, Susan, additional, Fegan, Greg, additional, Davies, Jan, additional, Foster, Theresa, additional, Francis, Nick, additional, Gao Smith, Fang, additional, Ellis, Gemma, additional, Shanahan, Tracy, additional, Howe, Robin, additional, Ricketts, Samuel, additional, and Snooks, Helen, additional

Published
2018
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166. PATRIC, the bacterial bioinformatics database and analysis resource

Author

Wattam, Alice R., Abraham, David, Dalay, Oral, Disz, Terry L., Driscoll, Timothy, Gabbard, Joseph L., Gillespie, Joseph J., Gough, Roger, Hix, Deborah, Kenyon, Ronald, Machi, Dustin, Mao, Chunhong, Nordberg, Eric K., Olson, Robert, Overbeek, Ross, Pusch, Gordon D., Shukla, Maulik, Schulman, Julie, Stevens, Rick L., Sullivan, Daniel E., Vonstein, Veronika, Warren, Andrew, Will, Rebecca, Wilson, Meredith J.C., Yoo, Hyun Seung, Zhang, Chengdong, Zhang, Yan, Sobral, Bruno W., Wattam, Alice R., Abraham, David, Dalay, Oral, Disz, Terry L., Driscoll, Timothy, Gabbard, Joseph L., Gillespie, Joseph J., Gough, Roger, Hix, Deborah, Kenyon, Ronald, Machi, Dustin, Mao, Chunhong, Nordberg, Eric K., Olson, Robert, Overbeek, Ross, Pusch, Gordon D., Shukla, Maulik, Schulman, Julie, Stevens, Rick L., Sullivan, Daniel E., Vonstein, Veronika, Warren, Andrew, Will, Rebecca, Wilson, Meredith J.C., Yoo, Hyun Seung, Zhang, Chengdong, Zhang, Yan, and Sobral, Bruno W.

Abstract

The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e.g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10 000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue

Published
2017

171. Efficacy and Safety of CTL019 in the First US Phase II Multicenter Trial in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia: Results of an Interim Analysis

Author

Maude, Shannon L, primary, Pulsipher, Michael A, additional, Boyer, Michael W, additional, Grupp, Stephan A, additional, Davies, Stella M, additional, Phillips, Christine L, additional, Verneris, Michael R, additional, August, Keith J, additional, Schlis, Krysta, additional, Driscoll, Timothy A, additional, Mody, Rajen, additional, Capitini, Christian M, additional, June, Carl H, additional, Levine, Bruce L, additional, Wood, Patricia A, additional, Yi, Lan, additional, and Levine, John E, additional

Published
2016
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172. Conjugative Transposons and Their Cargo Genes Vary across Natural Populations of Rickettsia buchneri Infecting the Tick Ixodes scapularis.

Author

Hagen, Rachael, Verhoeve, Victoria I, Gillespie, Joseph J, and Driscoll, Timothy P

Subjects
RICKETTSIA, TRANSPOSONS, IXODES scapularis, INTRODUCED species, POLYMERASE chain reaction, ENDOPARASITES
Abstract

Rickettsia buchneri (formerly Rickettsia endosymbiont of Ixodes scapularis, or REIS) is an obligate intracellular endoparasite of the black-legged tick, the primary vector of Lyme disease in North America. It is noteworthy among the rickettsiae for its relatively large genome (1.8 Mb) and extraordinary proliferation of mobile genetic elements (MGEs), which comprise nearly 35% of its genome. Previous analysis of the R. buchneri genome identified several integrative conjugative elements named Rickettsiales amplified genomic elements (RAGEs); the composition of these RAGEs suggests that continued genomic invasions by MGEs facilitated the proliferation of rickettsial genes related to an intracellular lifestyle. In this study, we compare the genomic diversity at RAGE loci among sequenced rickettsiae that infect three related Ixodes spp. including two strains of R. buchneri and Rickettsia endosymbiont of Ixodes pacificus strain Humboldt, as well as a closely related species R. tamurae infecting Amblyomma testudinarium ticks. We further develop a novel multiplex droplet digital PCR assay and use it to quantify copy number ratios of chromosomal R. buchneri RAGE-A and RAGE-B to the single-copy gene gltA within natural populations of I. scapularis. Our results reveal substantial diversity among R. buchneri at these loci, both within individual ticks as well as in the I. scapularis population at large, demonstrating that genomic rearrangement of MGEs is an active process in these intracellular bacteria. [ABSTRACT FROM AUTHOR]

Published
2018
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173. Genomic insights into the Ixodes scapularis tick vector of Lyme disease

Author

Gulia-Nuss, Monika, Nuss, Andrew B., Meyer, Jason M., Sonenshine, Daniel E., Roe, R. Michael, Waterhouse, Robert M., Sattelle, David B., de la Fuente, Jose, Ribeiro, Jose M., Megy, Karine, Thimmapuram, Jyothi, Miller, Jason R., Walenz, Brian P., Koren, Sergey, Hostetler, Jessica B., Thiagarajan, Mathangi, Joardar, Vinita S., Hannick, Linda I., Bidwell, Shelby, Hammond, Martin P., Young, Sarah, Zeng, Qiandong, Abrudan, Jenica L., Almeida, Francisca C., Ayllon, Nieves, Bhide, Ketaki, Bissinger, Brooke W., Bonzon-Kulichenko, Elena, Buckingham, Steven D., Caffrey, Daniel R., Caimano, Melissa J., Croset, Vincent, Driscoll, Timothy, Gilbert, Don, Gillespie, Joseph J., Giraldo-Calderon, Gloria I., Grabowski, Jeffrey M., Jiang, David, Khalil, Sayed M. S., Kim, Donghun, Kocan, Katherine M., Koci, Juraj, Kuhn, Richard J., Kurtti, Timothy J., Lees, Kristin, Lang, Emma G., Kennedy, Ryan C., Kwon, Hyeogsun, Perera, Rushika, Qi, Yumin, Radolf, Justin D., Sakamoto, Joyce M., Sanchez-Gracia, Alejandro, Severo, Maiara S., Silverman, Neal, Simo, Ladislav, Tojo, Marta, Tornador, Cristian, Van Zee, Janice P., Vazquez, Jesus, Vieira, Filipe G., Villar, Margarita, Wespiser, Adam R., Yang, Yunlong, Zhu, Jiwei, Arensburger, Peter, Pietrantonio, Patricia V., Barker, Stephen C., Shao, Renfu, Zdobnov, Evgeny M., Hauser, Frank, Grimmelikhuijzen, Cornelis J. P., Park, Yoonseong, Rozas, Julio, Benton, Richard, Pedra, Joao H. F., Nelson, David R., Unger, Maria F., Tubio, Jose M. C., Tu, Zhijian Jake, Robertson, Hugh M., Shumway, Martin, Sutton, Granger, Wortman, Jennifer R., Lawson, Daniel, Wikel, Stephen K., Nene, Vishvanath M., Fraser, Claire M., Collins, Frank H., Birren, Bruce, Nelson, Karen E., Caler, Elisabet, Hill, Catherine A., Gulia-Nuss, Monika, Nuss, Andrew B., Meyer, Jason M., Sonenshine, Daniel E., Roe, R. Michael, Waterhouse, Robert M., Sattelle, David B., de la Fuente, Jose, Ribeiro, Jose M., Megy, Karine, Thimmapuram, Jyothi, Miller, Jason R., Walenz, Brian P., Koren, Sergey, Hostetler, Jessica B., Thiagarajan, Mathangi, Joardar, Vinita S., Hannick, Linda I., Bidwell, Shelby, Hammond, Martin P., Young, Sarah, Zeng, Qiandong, Abrudan, Jenica L., Almeida, Francisca C., Ayllon, Nieves, Bhide, Ketaki, Bissinger, Brooke W., Bonzon-Kulichenko, Elena, Buckingham, Steven D., Caffrey, Daniel R., Caimano, Melissa J., Croset, Vincent, Driscoll, Timothy, Gilbert, Don, Gillespie, Joseph J., Giraldo-Calderon, Gloria I., Grabowski, Jeffrey M., Jiang, David, Khalil, Sayed M. S., Kim, Donghun, Kocan, Katherine M., Koci, Juraj, Kuhn, Richard J., Kurtti, Timothy J., Lees, Kristin, Lang, Emma G., Kennedy, Ryan C., Kwon, Hyeogsun, Perera, Rushika, Qi, Yumin, Radolf, Justin D., Sakamoto, Joyce M., Sanchez-Gracia, Alejandro, Severo, Maiara S., Silverman, Neal, Simo, Ladislav, Tojo, Marta, Tornador, Cristian, Van Zee, Janice P., Vazquez, Jesus, Vieira, Filipe G., Villar, Margarita, Wespiser, Adam R., Yang, Yunlong, Zhu, Jiwei, Arensburger, Peter, Pietrantonio, Patricia V., Barker, Stephen C., Shao, Renfu, Zdobnov, Evgeny M., Hauser, Frank, Grimmelikhuijzen, Cornelis J. P., Park, Yoonseong, Rozas, Julio, Benton, Richard, Pedra, Joao H. F., Nelson, David R., Unger, Maria F., Tubio, Jose M. C., Tu, Zhijian Jake, Robertson, Hugh M., Shumway, Martin, Sutton, Granger, Wortman, Jennifer R., Lawson, Daniel, Wikel, Stephen K., Nene, Vishvanath M., Fraser, Claire M., Collins, Frank H., Birren, Bruce, Nelson, Karen E., Caler, Elisabet, and Hill, Catherine A.

Abstract

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing similar to 57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.

Published
2016
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174. Genomic insights into the Ixodes scapularis tick vector of Lyme disease

Author

Biochemistry, Fralin Life Sciences Institute, Gulia-Nuss, Monika, Nuss, Andrew B., Meyer, Jason M., Sonenshine, Daniel E., Roe, R. Michael, Waterhouse, Robert M., Sattelle, David B., de la Fuente, Jose, Ribeiro, Jose M., Megy, Karine, Thimmapuram, Jyothi, Miller, Jason R., Walenz, Brian P., Koren, Sergey, Hostetler, Jessica B., Thiagarajan, Mathangi, Joardar, Vinita S., Hannick, Linda I., Bidwell, Shelby, Hammond, Martin P., Young, Sarah, Zeng, Qiandong, Abrudan, Jenica L., Almeida, Francisca C., Ayllon, Nieves, Bhide, Ketaki, Bissinger, Brooke W., Bonzon-Kulichenko, Elena, Buckingham, Steven D., Caffrey, Daniel R., Caimano, Melissa J., Croset, Vincent, Driscoll, Timothy, Gilbert, Don, Gillespie, Joseph J., Giraldo-Calderon, Gloria I., Grabowski, Jeffrey M., Jiang, David, Khalil, Sayed M. S., Kim, Donghun, Kocan, Katherine M., Koci, Juraj, Kuhn, Richard J., Kurtti, Timothy J., Lees, Kristin, Lang, Emma G., Kennedy, Ryan C., Kwon, Hyeogsun, Perera, Rushika, Qi, Yumin, Radolf, Justin D., Sakamoto, Joyce M., Sanchez-Gracia, Alejandro, Severo, Maiara S., Silverman, Neal, Simo, Ladislav, Tojo, Marta, Tornador, Cristian, Van Zee, Janice P., Vazquez, Jesus, Vieira, Filipe G., Villar, Margarita, Wespiser, Adam R., Yang, Yunlong, Zhu, Jiwei, Arensburger, Peter, Pietrantonio, Patricia V., Barker, Stephen C., Shao, Renfu, Zdobnov, Evgeny M., Hauser, Frank, Grimmelikhuijzen, Cornelis J. P., Park, Yoonseong, Rozas, Julio, Benton, Richard, Pedra, Joao H. F., Nelson, David R., Unger, Maria F., Tubio, Jose M. C., Tu, Zhijian Jake, Robertson, Hugh M., Shumway, Martin, Sutton, Granger, Wortman, Jennifer R., Lawson, Daniel, Wikel, Stephen K., Nene, Vishvanath M., Fraser, Claire M., Collins, Frank H., Birren, Bruce, Nelson, Karen E., Caler, Elisabet, Hill, Catherine A., Biochemistry, Fralin Life Sciences Institute, Gulia-Nuss, Monika, Nuss, Andrew B., Meyer, Jason M., Sonenshine, Daniel E., Roe, R. Michael, Waterhouse, Robert M., Sattelle, David B., de la Fuente, Jose, Ribeiro, Jose M., Megy, Karine, Thimmapuram, Jyothi, Miller, Jason R., Walenz, Brian P., Koren, Sergey, Hostetler, Jessica B., Thiagarajan, Mathangi, Joardar, Vinita S., Hannick, Linda I., Bidwell, Shelby, Hammond, Martin P., Young, Sarah, Zeng, Qiandong, Abrudan, Jenica L., Almeida, Francisca C., Ayllon, Nieves, Bhide, Ketaki, Bissinger, Brooke W., Bonzon-Kulichenko, Elena, Buckingham, Steven D., Caffrey, Daniel R., Caimano, Melissa J., Croset, Vincent, Driscoll, Timothy, Gilbert, Don, Gillespie, Joseph J., Giraldo-Calderon, Gloria I., Grabowski, Jeffrey M., Jiang, David, Khalil, Sayed M. S., Kim, Donghun, Kocan, Katherine M., Koci, Juraj, Kuhn, Richard J., Kurtti, Timothy J., Lees, Kristin, Lang, Emma G., Kennedy, Ryan C., Kwon, Hyeogsun, Perera, Rushika, Qi, Yumin, Radolf, Justin D., Sakamoto, Joyce M., Sanchez-Gracia, Alejandro, Severo, Maiara S., Silverman, Neal, Simo, Ladislav, Tojo, Marta, Tornador, Cristian, Van Zee, Janice P., Vazquez, Jesus, Vieira, Filipe G., Villar, Margarita, Wespiser, Adam R., Yang, Yunlong, Zhu, Jiwei, Arensburger, Peter, Pietrantonio, Patricia V., Barker, Stephen C., Shao, Renfu, Zdobnov, Evgeny M., Hauser, Frank, Grimmelikhuijzen, Cornelis J. P., Park, Yoonseong, Rozas, Julio, Benton, Richard, Pedra, Joao H. F., Nelson, David R., Unger, Maria F., Tubio, Jose M. C., Tu, Zhijian Jake, Robertson, Hugh M., Shumway, Martin, Sutton, Granger, Wortman, Jennifer R., Lawson, Daniel, Wikel, Stephen K., Nene, Vishvanath M., Fraser, Claire M., Collins, Frank H., Birren, Bruce, Nelson, Karen E., Caler, Elisabet, and Hill, Catherine A.

Abstract

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing similar to 57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.

Published
2016

175. Genomic insights into the Ixodes scapularis tick vector of Lyme disease

Author

National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Australian Research Council, Ministerio de Ciencia e Innovación (España), National Science Foundation (US), Xunta de Galicia, European Commission, Department of Agriculture (US), Texas AgriLife Research, European Research Council, Swiss National Science Foundation, Boehringer Ingelheim Fonds, Fundação para a Ciência e a Tecnologia (Portugal), Lundbeck Foundation, Gulia-Nuss, Monika, Nuss, Andrew B., Meyer, Jason M., Sonenshine, Daniel E., Roe, R. Michael, Waterhouse, Robert M., Sattelle, David B., Fuente, José de la, Ribeiro, Jose M., Megy, Karine, Thimmapuram, Jyothi, Miller, Jason R., Walenz, Brian P., Koren, Sergey, Hostetler, Jessica B., Thiagarajan, Mathangi, Joardar, Vinita S., Hannick, Linda I., Bidwell, Shelby, Hammond, Martin P., Young, Sarah, Zeng, Qiandong, Abrudan, Jenica L., Almeida, Francisca C., Ayllón, Nieves, Bhide, Ketaki, Bissinger, Brooke W., Bonzón-Kulichenko, Elena, Buckingham, Steven D., Caffrey, Daniel R., Caimano, Melissa J., Croset, Vincent, Driscoll, Timothy, Gilbert, Don, Gillespie, Joseph J., Giraldo-Calderón, Gloria I., Grabowski, Jeffrey M., Jiang, David, Khalil, Sayed M .S., Kim, Donghun, Kocan, Katherine M., Koči, Juraj, Kuhn, Richard J., Kurtti, Timothy J., Lees, Kristin, Lang, Emma G., Kennedy, Ryan C., Kwon, Hyeogsun, Perera, Rushika, Qi, Yumin, Radolf, Justin D., Sakamoto, Joyce M., Sánchez-Gracia, Alejandro, Severo, Maiara S., Silverman, Neal, Šimo, Ladislav, Tojo, Marta, Tornador, Cristian, Van Zee, Janice P., Vázquez, Jesús, Vieira, Filipe G., Villar, Margarita, Wespiser, Adam R., Yang, Yunlong, Zhu, Jiwei, Arensburger, Peter, Pietrantonio, Patricia V., Barker, Stephen C., Shao, Renfu, Zdobnov, Evgeny M., Hauser, Frank, Grimmelikhuijzen, Cornelis J. P., Park, Yoonseong, Rozas, Julio, Benton, Richard, Pedra, Joao H. F., Nelson, David R., Unger, Maria F., Tubio, Jose M. C., Tu, Zhijian, Robertson, Hugh M., Shumway, Martin, Sutton, Granger, Wortman, Jennifer R., Lawson, Daniel, Wikel, Stephen K., Nene, Vishvanath M., Fraser, Claire M., Collins, Frank H., Birren, Bruce, Nelson, Karen E., Caler, Elisabet, Hill, Catherine A., National Institute of Allergy and Infectious Diseases (US), National Institutes of Health (US), Department of Health and Human Services (US), Australian Research Council, Ministerio de Ciencia e Innovación (España), National Science Foundation (US), Xunta de Galicia, European Commission, Department of Agriculture (US), Texas AgriLife Research, European Research Council, Swiss National Science Foundation, Boehringer Ingelheim Fonds, Fundação para a Ciência e a Tecnologia (Portugal), Lundbeck Foundation, Gulia-Nuss, Monika, Nuss, Andrew B., Meyer, Jason M., Sonenshine, Daniel E., Roe, R. Michael, Waterhouse, Robert M., Sattelle, David B., Fuente, José de la, Ribeiro, Jose M., Megy, Karine, Thimmapuram, Jyothi, Miller, Jason R., Walenz, Brian P., Koren, Sergey, Hostetler, Jessica B., Thiagarajan, Mathangi, Joardar, Vinita S., Hannick, Linda I., Bidwell, Shelby, Hammond, Martin P., Young, Sarah, Zeng, Qiandong, Abrudan, Jenica L., Almeida, Francisca C., Ayllón, Nieves, Bhide, Ketaki, Bissinger, Brooke W., Bonzón-Kulichenko, Elena, Buckingham, Steven D., Caffrey, Daniel R., Caimano, Melissa J., Croset, Vincent, Driscoll, Timothy, Gilbert, Don, Gillespie, Joseph J., Giraldo-Calderón, Gloria I., Grabowski, Jeffrey M., Jiang, David, Khalil, Sayed M .S., Kim, Donghun, Kocan, Katherine M., Koči, Juraj, Kuhn, Richard J., Kurtti, Timothy J., Lees, Kristin, Lang, Emma G., Kennedy, Ryan C., Kwon, Hyeogsun, Perera, Rushika, Qi, Yumin, Radolf, Justin D., Sakamoto, Joyce M., Sánchez-Gracia, Alejandro, Severo, Maiara S., Silverman, Neal, Šimo, Ladislav, Tojo, Marta, Tornador, Cristian, Van Zee, Janice P., Vázquez, Jesús, Vieira, Filipe G., Villar, Margarita, Wespiser, Adam R., Yang, Yunlong, Zhu, Jiwei, Arensburger, Peter, Pietrantonio, Patricia V., Barker, Stephen C., Shao, Renfu, Zdobnov, Evgeny M., Hauser, Frank, Grimmelikhuijzen, Cornelis J. P., Park, Yoonseong, Rozas, Julio, Benton, Richard, Pedra, Joao H. F., Nelson, David R., Unger, Maria F., Tubio, Jose M. C., Tu, Zhijian, Robertson, Hugh M., Shumway, Martin, Sutton, Granger, Wortman, Jennifer R., Lawson, Daniel, Wikel, Stephen K., Nene, Vishvanath M., Fraser, Claire M., Collins, Frank H., Birren, Bruce, Nelson, Karen E., Caler, Elisabet, and Hill, Catherine A.

Abstract

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.

Published
2016

176. Farm-related fatalities involving children in Australia, 1989-92

Author

Mitchell, Rebecca J., Franklin, Richard C., Driscoll, Timothy R., and Fragar, Lyn J.

Subjects
Children -- Patient outcomes, Rural children -- Accidents, Agriculture -- Accidents, Health
Abstract

Objective: To describe the types of and circumstances surrounding unintentional farm-related fatal injuries involving children aged less than 15 years in Australia. Methods: Information concerning 115 deaths were obtained from inspection of coronial files for the period 1989-92. Results: Children less than 15 years made up 20% of all unintentional farm-related fatalities in Australia, with children less than 5 years representing 63% of all child fatalities. The majority of children were fatally injured while bystanders to farm work and equipment used on the farm (including dams), with drowning the most common mechanism of the fatal incident for children aged both 5 years or less and 5-9 years. Vehicle accidents were common for children aged 10-14 years. Conclusions: Children are exposed to various hazards in the farming environment and as such are at risk of being injured. Implications: This study has highlighted a number of particular hazards for children on farms, with drowning, transport and tractor-related injuries of particular concern. A national strategy for child safety on farms has been developed by Farmsafe Australia aimed at providing a nationally co-ordinated plan for improving child safety on farms.

Published
2001

179. TheRickettsiatype IV secretion system: unrealized complexity mired by gene family expansion

Author

Gillespie, Joseph J., primary, Phan, Isabelle Q. H., additional, Driscoll, Timothy P., additional, Guillotte, Mark L., additional, Lehman, Stephanie S., additional, Rennoll-Bankert, Kristen E., additional, Subramanian, Sandhya, additional, Beier-Sexton, Magda, additional, Myler, Peter J., additional, Rahman, M. Sayeedur, additional, and Azad, Abdu F., additional

Published
2016
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183. Genomic insights into the Ixodes scapularis tick vector of Lyme disease

Author

Gulia-Nuss, Monika, primary, Nuss, Andrew B., additional, Meyer, Jason M., additional, Sonenshine, Daniel E., additional, Roe, R. Michael, additional, Waterhouse, Robert M., additional, Sattelle, David B., additional, de la Fuente, José, additional, Ribeiro, Jose M., additional, Megy, Karine, additional, Thimmapuram, Jyothi, additional, Miller, Jason R., additional, Walenz, Brian P., additional, Koren, Sergey, additional, Hostetler, Jessica B., additional, Thiagarajan, Mathangi, additional, Joardar, Vinita S., additional, Hannick, Linda I., additional, Bidwell, Shelby, additional, Hammond, Martin P., additional, Young, Sarah, additional, Zeng, Qiandong, additional, Abrudan, Jenica L., additional, Almeida, Francisca C., additional, Ayllón, Nieves, additional, Bhide, Ketaki, additional, Bissinger, Brooke W., additional, Bonzon-Kulichenko, Elena, additional, Buckingham, Steven D., additional, Caffrey, Daniel R., additional, Caimano, Melissa J., additional, Croset, Vincent, additional, Driscoll, Timothy, additional, Gilbert, Don, additional, Gillespie, Joseph J., additional, Giraldo-Calderón, Gloria I., additional, Grabowski, Jeffrey M., additional, Jiang, David, additional, Khalil, Sayed M. S., additional, Kim, Donghun, additional, Kocan, Katherine M., additional, Koči, Juraj, additional, Kuhn, Richard J., additional, Kurtti, Timothy J., additional, Lees, Kristin, additional, Lang, Emma G., additional, Kennedy, Ryan C., additional, Kwon, Hyeogsun, additional, Perera, Rushika, additional, Qi, Yumin, additional, Radolf, Justin D., additional, Sakamoto, Joyce M., additional, Sánchez-Gracia, Alejandro, additional, Severo, Maiara S., additional, Silverman, Neal, additional, Šimo, Ladislav, additional, Tojo, Marta, additional, Tornador, Cristian, additional, Van Zee, Janice P., additional, Vázquez, Jesús, additional, Vieira, Filipe G., additional, Villar, Margarita, additional, Wespiser, Adam R., additional, Yang, Yunlong, additional, Zhu, Jiwei, additional, Arensburger, Peter, additional, Pietrantonio, Patricia V., additional, Barker, Stephen C., additional, Shao, Renfu, additional, Zdobnov, Evgeny M., additional, Hauser, Frank, additional, Grimmelikhuijzen, Cornelis J. P., additional, Park, Yoonseong, additional, Rozas, Julio, additional, Benton, Richard, additional, Pedra, Joao H. F., additional, Nelson, David R., additional, Unger, Maria F., additional, Tubio, Jose M. C., additional, Tu, Zhijian, additional, Robertson, Hugh M., additional, Shumway, Martin, additional, Sutton, Granger, additional, Wortman, Jennifer R., additional, Lawson, Daniel, additional, Wikel, Stephen K., additional, Nene, Vishvanath M., additional, Fraser, Claire M., additional, Collins, Frank H., additional, Birren, Bruce, additional, Nelson, Karen E., additional, Caler, Elisabet, additional, and Hill, Catherine A., additional

Published
2016
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184. The Complete Genome Sequence of the Emerging Pathogen Mycobacterium haemophilum Explains Its Unique Culture Requirements

Author

Tufariello, JoAnn M., Kerantzas, Christopher A., Vilcheze, Catherine, Calder, R. Brent, Nordberg, Eric K., Fischer, Jack A., Hartman, Travis E., Yang, Eva, Driscoll, Timothy, Cole, Laura E., Sebra, Robert, Maqbool, Shahina B., Wattam, Alice R., Jacobs, William R. Jr., Tufariello, JoAnn M., Kerantzas, Christopher A., Vilcheze, Catherine, Calder, R. Brent, Nordberg, Eric K., Fischer, Jack A., Hartman, Travis E., Yang, Eva, Driscoll, Timothy, Cole, Laura E., Sebra, Robert, Maqbool, Shahina B., Wattam, Alice R., and Jacobs, William R. Jr.

Abstract

Mycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals. M. haemophilum exhibits a unique requirement for iron supplementation to support its growth in culture, but the basis for this property and how it may shape pathogenesis is unclear. Using a combination of Illumina, PacBio, and Sanger sequencing, the complete genome sequence of M. haemophilum was determined. Guided by this sequence, experiments were performed to define the basis for the unique growth requirements of M. haemophilum. We found that M. haemophilum, unlike many other mycobacteria, is unable to synthesize iron-binding siderophores known as mycobactins or to utilize ferri-mycobactins to support growth. These differences correlate with the absence of genes associated with mycobactin synthesis, secretion, and uptake. In agreement with the ability of heme to promote growth, we identified genes encoding heme uptake machinery. Consistent with its propensity to infect the skin, we show at the whole-genome level the genetic closeness of M. haemophilum with Mycobacterium leprae, an organism which cannot be cultivated in vitro, and we identify genes uniquely shared by these organisms. Finally, we identify means to express foreign genes in M. haemophilum. These data explain the unique culture requirements for this important pathogen, provide a foundation upon which the genome sequence can be exploited to improve diagnostics and therapeutics, and suggest use of M. haemophilum as a tool to elucidate functions of genes shared with M. leprae. IMPORTANCE Mycobacterium haemophilum is an emerging pathogen with an unknown natural reservoir that exhibits unique requirements for iron supplementation to grow in vitro. Understanding the basis for this iron requirement is important because it is fundamental to isolation of the organism from clinical samples and environmental sources. Defining the molecular basis for M.

Published
2015
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185. The Complete Genome Sequence of the Emerging Pathogen Mycobacterium haemophilum Explains Its Unique Culture Requirements

Author

Tufariello, JoAnn M., primary, Kerantzas, Christopher A., additional, Vilchèze, Catherine, additional, Calder, R. Brent, additional, Nordberg, Eric K., additional, Fischer, Jack A., additional, Hartman, Travis E., additional, Yang, Eva, additional, Driscoll, Timothy, additional, Cole, Laura E., additional, Sebra, Robert, additional, Maqbool, Shahina B., additional, Wattam, Alice R., additional, and Jacobs, William R., additional

Published
2015
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187. Host-Microbe Relations: A Phylogenomics-Driven Bioinformatic Approach to the Characterization of Microbial DNA from Heterogeneous Sequence Data

Author

Driscoll, Timothy, Animal and Poultry Sciences, Bevan, David R., Gillespie, Joe Michael, Marathe, Madhav Vishnu, and Murali, T. M.

Subjects
genomics, phylogenomics, genome-mining, bioinformatics, bacteria, lateral gene transfer, symbiosis, host-microbe interactions
Abstract

Plants and animals are characterized by intimate, enduring, often indispensable, and always complex associations with microbes. Therefore, it should come as no surprise that when the genome of a eukaryote is sequenced, a medley of bacterial sequences are produced as well. These sequences can be highly informative about the interactions between the eukaryote and its bacterial cohorts; unfortunately, they often comprise a vanishingly small constituent within a heterogeneous mixture of microbial and host sequences. Genomic analyses typically avoid the bacterial sequences in order to obtain a genome sequence for the host. Metagenomic analysis typically avoid the host sequences in order to analyze community composition and functional diversity of the bacterial component. This dissertation describes the development of a novel approach at the intersection of genomics and metagenomics, aimed at the extraction and characterization of bacterial sequences from heterogeneous sequence data using phylogenomic and bioinformatic tools. To achieve this objective, three interoperable workflows were constructed as modular computational pipelines, with built-in checkpoints for periodic interpretation and refinement. The MetaMiner workflow uses 16S small subunit rDNA analysis to enable the systematic discovery and classification of bacteria associated with a host genome sequencing project. Using this information, the ReadMiner workflow comprehensively extracts, assembles, and characterizes sequences that belong to a target microbe. Finally, AssemblySifter examines the genes and scaffolds of the eukaryotic genome for sequences associated with the target microbe. The combined information from these three workflows is used to systemically characterize a bacterial target of interest, including robust estimation of its phylogeny, assessment of its signature profile, and determination of its relationship to the associated eukaryote. This dissertation presents the development of the described methodology and its application to three eukaryotic genome projects. In the first study, the genomic sequences of a single, known endosymbiont was extracted from the genome sequencing data of its host. In the second study, a highly divergent endosymbiont was characterized from the assembled genome of its host. In the third study, genome sequences from a novel bacterium were extracted from both the raw sequencing data and assembled genome of a eukaryote that contained significant amounts of sequence from multiple competing bacteria. Taken together, these results demonstrate the usefulness of the described approach in singularly disparate situations, and strongly argue for a sophisticated, multifaceted, supervised approach to the characterization of host-associated microbes and their interactions. Ph. D.

Published
2013

188. Augmented Human Inspired Phase Variable Using a Canonical Dynamical System

Author

Driscoll, Timothy

Subjects
Biomedical, Electrical and Computer Engineering
Abstract

Accurately parameterizing human gait is highly important in the continued development of assistive robotics, including but not limited to lower limb prostheses and exoskeletons. Previous studies introduce the idea of time-invariant real-time gait parameterization via human-inspired phase variables. The phase represents the location or percent of the gait cycle the user has progressed through. This thesis proposes an alternative approach for determining the gait phase leveraging previous methods and a canonical dynamical system. Human subject experiments demonstrate the ability to accurately produce a phase variable corresponding to the human gait progression for various walking configurations. Configurations include changes in incline and speed. Results show an augmented real-time approach capable of adapting to different walking conditions.

Published
2023

197. PATRIC, the bacterial bioinformatics database and analysis resource

Author

Wattam, Alice R., Abraham, David, Dalay, Oral, Disz, Terry L., Driscoll, Timothy, Gabbard, Joseph L., Gillespie, Joseph J., Gough, Roger, Hix, Deborah, Kenyon, Ronald W., Machi, Dustin, Mao, Chunhong, Nordberg, Eric K., Olson, Robert, Overbeek, Ross, Pusch, Gordon D., Shukla, Maulik, Schulman, Julie, Stevens, Rick L., Sullivan, Daniel E., Vonstein, Veronika, Warren, Andrew S., Will, Rebecca, Wilson, Meredith J. C., Yoo, Hyunseung, Zhang, Chengdong, Zhang, Yan, Sobral, Bruno W., Wattam, Alice R., Abraham, David, Dalay, Oral, Disz, Terry L., Driscoll, Timothy, Gabbard, Joseph L., Gillespie, Joseph J., Gough, Roger, Hix, Deborah, Kenyon, Ronald W., Machi, Dustin, Mao, Chunhong, Nordberg, Eric K., Olson, Robert, Overbeek, Ross, Pusch, Gordon D., Shukla, Maulik, Schulman, Julie, Stevens, Rick L., Sullivan, Daniel E., Vonstein, Veronika, Warren, Andrew S., Will, Rebecca, Wilson, Meredith J. C., Yoo, Hyunseung, Zhang, Chengdong, Zhang, Yan, and Sobral, Bruno W.

Abstract

The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e. g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10 000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue.

Published
2014
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198. A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases.

Author

Parikh, Suhag H, Parikh, Suhag H, Mendizabal, Adam, Benjamin, Cara L, Komanduri, Krishna V, Antony, Jeyaraj, Petrovic, Aleksandra, Hale, Gregory, Driscoll, Timothy A, Martin, Paul L, Page, Kristin M, Flickinger, Ketti, Moffet, Jerelyn, Niedzwiecki, Donna, Kurtzberg, Joanne, Szabolcs, Paul, Parikh, Suhag H, Parikh, Suhag H, Mendizabal, Adam, Benjamin, Cara L, Komanduri, Krishna V, Antony, Jeyaraj, Petrovic, Aleksandra, Hale, Gregory, Driscoll, Timothy A, Martin, Paul L, Page, Kristin M, Flickinger, Ketti, Moffet, Jerelyn, Niedzwiecki, Donna, Kurtzberg, Joanne, and Szabolcs, Paul

Abstract

Reduced-intensity conditioning (RIC) regimens have the potential to decrease transplantation-related morbidity and mortality. However, engraftment failure has been prohibitively high after RIC unrelated umbilical cord blood transplantation (UCBT) in chemotherapy-naïve children with nonmalignant diseases (NMD). Twenty-two children with a median age of 2.8 years, many with severe comorbidities and prior viral infections, were enrolled in a novel RIC protocol consisting of hydroxyurea, alemtuzumab, fludarabine, melphalan, and thiotepa followed by single UCBT. Patients underwent transplantation for inherited metabolic disorders (n = 8), primary immunodeficiencies (n = 9), hemoglobinopathies (n = 4) and Diamond Blackfan anemia (n = 1). Most umbilical cord blood (UCB) units were HLA-mismatched with median infused total nucleated cell dose of 7.9 × 10(7)/kg. No serious organ toxicities were attributable to the regimen. The cumulative incidence of neutrophil engraftment was 86.4% (95% confidence interval [CI], 65% to 100%) in a median of 20 days, with the majority sustaining > 95% donor chimerism at 1 year. Cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV by day 180 was 27.3% (95% CI, 8.7% to 45.9%) and 13.6% (95 CI, 0% to 27.6%), respectively. Cumulative incidence of extensive chronic GVHD was 9.1% (95% CI, 0% to 20.8%). The primary causes of death were viral infections (n = 3), acute GVHD (n = 1) and transfusion reaction (n = 1). One-year overall and event-free survivals were 77.3% (95% CI, 53.7% to 89.8%) and 68.2% (95% CI, 44.6% to 83.4%) with 31 months median follow-up. This is the first RIC protocol demonstrating durable UCB engraftment in children with NMD. Future risk-based modifications of this regimen could decrease the incidence of viral infections. (www.clinicaltrials.gov/NCT00744692).

Published
2014

199. PATRIC, the bacterial bioinformatics database and analysis resource

Author

Fralin Life Sciences Institute, Industrial and Systems Engineering, Wattam, Alice R., Abraham, David, Dalay, Oral, Disz, Terry L., Driscoll, Timothy, Gabbard, Joseph L., Gillespie, Joseph J., Gough, Roger, Hix, Deborah, Kenyon, Ronald W., Machi, Dustin, Mao, Chunhong, Nordberg, Eric K., Olson, Robert, Overbeek, Ross, Pusch, Gordon D., Shukla, Maulik, Schulman, Julie, Stevens, Rick L., Sullivan, Daniel E., Vonstein, Veronika, Warren, Andrew S., Will, Rebecca, Wilson, Meredith J. C., Yoo, Hyunseung, Zhang, Chengdong, Zhang, Yan, Sobral, Bruno, Fralin Life Sciences Institute, Industrial and Systems Engineering, Wattam, Alice R., Abraham, David, Dalay, Oral, Disz, Terry L., Driscoll, Timothy, Gabbard, Joseph L., Gillespie, Joseph J., Gough, Roger, Hix, Deborah, Kenyon, Ronald W., Machi, Dustin, Mao, Chunhong, Nordberg, Eric K., Olson, Robert, Overbeek, Ross, Pusch, Gordon D., Shukla, Maulik, Schulman, Julie, Stevens, Rick L., Sullivan, Daniel E., Vonstein, Veronika, Warren, Andrew S., Will, Rebecca, Wilson, Meredith J. C., Yoo, Hyunseung, Zhang, Chengdong, Zhang, Yan, and Sobral, Bruno

Abstract

The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e. g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10 000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue.

Published
2014

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