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1. Organ Size Control Is Dominant over Rb Family Inactivation to Restrict Proliferation In Vivo

Author

Ehmer, Ursula, Zmoos, Anne-Flore, Auerbach, Raymond K, Vaka, Dedeepya, Butte, Atul J, Kay, Mark A, and Sage, Julien

Subjects
Biochemistry and Cell Biology, Biological Sciences, Digestive Diseases, Cancer, Genetics, Liver Disease, 1.1 Normal biological development and functioning, Generic health relevance, ADP-Ribosylation Factors, Adaptor Proteins, Signal Transducing, Animals, Cell Cycle Proteins, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21, Genes, cdc, Hepatocytes, Liver, Mice, Organ Size, Phosphoproteins, Retinoblastoma-Like Protein p107, Retinoblastoma-Like Protein p130, Tumor Suppressor Protein p53, YAP-Signaling Proteins, Medical Physiology, Biological sciences
Abstract

In mammals, a cell's decision to divide is thought to be under the control of the Rb/E2F pathway. We previously found that inactivation of the Rb family of cell cycle inhibitors (Rb, p107, and p130) in quiescent liver progenitors leads to uncontrolled division and cancer initiation. Here, we show that, in contrast, deletion of the entire Rb gene family in mature hepatocytes is not sufficient for their long-term proliferation. The cell cycle block in Rb family mutant hepatocytes is independent of the Arf/p53/p21 checkpoint but can be abrogated upon decreasing liver size. At the molecular level, we identify YAP, a transcriptional regulator involved in organ size control, as a factor required for the sustained expression of cell cycle genes in hepatocytes. These experiments identify a higher level of regulation of the cell cycle in vivo in which signals regulating organ size are dominant regulators of the core cell cycle machinery.

Published
2014

3. Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project

Author

modENCODE Consortium, Gerstein, Mark B., Lu, Zhi John, Van Nostrand, Eric L., Cheng, Chao, Arshinoff, Bradley I., Liu, Tao, Yip, Kevin Y., Robilotto, Rebecca, Rechtsteiner, Andreas, Ikegami, Kohta, Alves, Pedro, Chateigner, Aurelien, Perry, Marc, Morris, Mitzi, Auerbach, Raymond K., Feng, Xin, Leng, Jing, Vielle, Anne, Niu, Wei, Rhrissorrakrai, Kahn, Agarwal, Ashish, Alexander, Roger P., Barber, Galt, Brdlik, Cathleen M., Brennan, Jennifer, Brouillet, Jeremy Jean, Carr, Adrian, Cheung, Ming-Sin, Clawson, Hiram, Contrino, Sergio, Dannenberg, Luke O., Dernburg, Abby F., Desai, Arshad, Dick, Lindsay, Dosé, Andréa C., Du, Jiang, Egelhofer, Thea, Ercan, Sevinc, Euskirchen, Ghia, Ewing, Brent, Feingold, Elise A., Gassmann, Reto, Good, Peter J., Green, Phil, Gullier, Francois, Gutwein, Michelle, Guyer, Mark S., Habegger, Lukas, Han, Ting, Henikoff, Jorja G., Henz, Stefan R., Hinrichs, Angie, Holster, Heather, Hyman, Tony, Iniguez, A. Leo, Janette, Judith, Jensen, Morten, Kato, Masaomi, Kent, W. James, Kephart, Ellen, Khivansara, Vishal, Khurana, Ekta, Kim, John K., Kolasinska-Zwierz, Paulina, Lai, Eric C., Latorre, Isabel, Leahey, Amber, Lewis, Suzanna, Lloyd, Paul, Lochovsky, Lucas, Lowdon, Rebecca F., Lubling, Yaniv, Lyne, Rachel, MacCoss, Michael, Mackowiak, Sebastian D., Mangone, Marco, McKay, Sheldon, Mecenas, Desirea, Merrihew, Gennifer, Miller, David M., Muroyama, Andrew, Murray, John I., Ooi, Siew-Loon, Pham, Hoang, Phippen, Taryn, Preston, Elica A., Rajewsky, Nikolaus, Rätsch, Gunnar, Rosenbaum, Heidi, Rozowsky, Joel, Rutherford, Kim, Ruzanov, Peter, Sarov, Mihail, Sasidharan, Rajkumar, Sboner, Andrea, Scheid, Paul, Segal, Eran, Shin, Hyunjin, Shou, Chong, Slack, Frank J., Slightam, Cindie, Smith, Richard, Spencer, William C., Stinson, E. O., Taing, Scott, Takasaki, Teruaki, Vafeados, Dionne, Voronina, Ksenia, Wang, Guilin, Washington, Nicole L., Whittle, Christina M., Wu, Beijing, Yan, Koon-Kiu, Zeller, Georg, Zha, Zheng, Zhong, Mei, Zhou, Xingliang, Ahringer, Julie, Strome, Susan, Gunsalus, Kristin C., Micklem, Gos, Liu, X. Shirley, Reinke, Valerie, Kim, Stuart K., Hillier, LaDeana W., Henikoff, Steven, Piano, Fabio, Snyder, Michael, Stein, Lincoln, Lieb, Jason D., and Waterston, Robert H.

Published
2010

5. An integrated encyclopedia of DNA elements in the human genome

Author

Dunham, Ian, Kundaje, Anshul, Aldred, Shelley F., Collins, Patrick J., Davis, Carrie A., Doyle, Francis, Epstein, Charles B., Frietze, Seth, Harrow, Jennifer, Kaul, Rajinder, Khatun, Jainab, Lajoie, Bryan R., Landt, Stephen G., Lee, Bum-Kyu, Pauli, Florencia, Rosenbloom, Kate R., Sabo, Peter, Safi, Alexias, Sanyal, Amartya, Shoresh, Noam, Simon, Jeremy M., Song, Lingyun, Trinklein, Nathan D., Altshuler, Robert C., Birney, Ewan, Brown, James B., Cheng, Chao, Djebali, Sarah, Dong, Xianjun, Ernst, Jason, Furey, Terrence S., Gerstein, Mark, Giardine, Belinda, Greven, Melissa, Hardison, Ross C., Harris, Robert S., Herrero, Javier, Hoffman, Michael M., Iyer, Sowmya, Kellis, Manolis, Kheradpour, Pouya, Lassmann, Timo, Li, Qunhua, Lin, Xinying, Marinov, Georgi K., Merkel, Angelika, Mortazavi, Ali, Parker, Stephen C. J., Reddy, Timothy E., Rozowsky, Joel, Schlesinger, Felix, Thurman, Robert E., Wang, Jie, Ward, Lucas D., Whitfield, Troy W., Wilder, Steven P., Wu, Weisheng, Xi, Hualin S., Yip, Kevin Y., Zhuang, Jiali, Bernstein, Bradley E., Green, Eric D., Gunter, Chris, Snyder, Michael, Pazin, Michael J., Lowdon, Rebecca F., Dillon, Laura A. L., Adams, Leslie B., Kelly, Caroline J., Zhang, Julia, Wexler, Judith R., Good, Peter J., Feingold, Elise A., Crawford, Gregory E., Dekker, Job, Elnitski, Laura, Farnham, Peggy J., Giddings, Morgan C., Gingeras, Thomas R., Guigo, Roderic, Hubbard, Timothy J., Kent, W. James, Lieb, Jason D., Margulies, Elliott H., Myers, Richard M., Stamatoyannopoulos, John A., Tenenbaum, Scott A., Weng, Zhiping, White, Kevin P., Wold, Barbara, Yu, Yanbao, Wrobel, John, Risk, Brian A., Gunawardena, Harsha P., Kuiper, Heather C., Maier, Christopher W., Xie, Ling, Chen, Xian, Mikkelsen, Tarjei S., Gillespie, Shawn, Goren, Alon, Ram, Oren, Zhang, Xiaolan, Wang, Li, Issner, Robbyn, Coyne, Michael J., Durham, Timothy, Ku, Manching, Truong, Thanh, Eaton, Matthew L., Dobin, Alex, Tanzer, Andrea, Lagarde, Julien, Lin, Wei, Xue, Chenghai, Williams, Brian A., Zaleski, Chris, Roder, Maik, Kokocinski, Felix, Abdelhamid, Rehab F., Alioto, Tyler, Antoshechkin, Igor, Baer, Michael T., Batut, Philippe, Bell, Ian, Bell, Kimberly, Chakrabortty, Sudipto, Chrast, Jacqueline, Curado, Joao, Derrien, Thomas, Drenkow, Jorg, Dumais, Erica, Dumais, Jackie, Duttagupta, Radha, Fastuca, Megan, Fejes-Toth, Kata, Ferreira, Pedro, Foissac, Sylvain, Fullwood, Melissa J., Gao, Hui, Gonzalez, David, Gordon, Assaf, Howald, Cedric, Jha, Sonali, Johnson, Rory, Kapranov, Philipp, King, Brandon, Kingswood, Colin, Li, Guoliang, Luo, Oscar J., Park, Eddie, Preall, Jonathan B., Presaud, Kimberly, Ribeca, Paolo, Robyr, Daniel, Ruan, Xiaoan, Sammeth, Michael, Sandhu, Kuljeet Singh, Schaeffer, Lorain, See, Lei-Hoon, Shahab, Atif, Skancke, Jorgen, Suzuki, Ana Maria, Takahashi, Hazuki, Tilgner, Hagen, Trout, Diane, Walters, Nathalie, Wang, Huaien, Hayashizaki, Yoshihide, Reymond, Alexandre, Antonarakis, Stylianos E., Hannon, Gregory J., Ruan, Yijun, Carninci, Piero, Sloan, Cricket A., Learned, Katrina, Malladi, Venkat S., Wong, Matthew C., Barber, Galt P., Cline, Melissa S., Dreszer, Timothy R., Heitner, Steven G., Karolchik, Donna, Kirkup, Vanessa M., Meyer, Laurence R., Long, Jeffrey C., Maddren, Morgan, Raney, Brian J., Grasfeder, Linda L., Giresi, Paul G., Battenhouse, Anna, Sheffield, Nathan C., Showers, Kimberly A., London, Darin, Bhinge, Akshay A., Shestak, Christopher, Schaner, Matthew R., Ki Kim, Seul, Zhang, Zhuzhu Z., Mieczkowski, Piotr A., Mieczkowska, Joanna O., Liu, Zheng, McDaniell, Ryan M., Ni, Yunyun, Rashid, Naim U., Kim, Min Jae, Adar, Sheera, Zhang, Zhancheng, Wang, Tianyuan, Winter, Deborah, Keefe, Damian, Iyer, Vishwanath R., Zheng, Meizhen, Wang, Ping, Gertz, Jason, Vielmetter, Jost, Partridge, E., Varley, Katherine E., Gasper, Clarke, Bansal, Anita, Pepke, Shirley, Jain, Preti, Amrhein, Henry, Bowling, Kevin M., Anaya, Michael, Cross, Marie K., Muratet, Michael A., Newberry, Kimberly M., McCue, Kenneth, Nesmith, Amy S., Fisher-Aylor, Katherine I., Pusey, Barbara, DeSalvo, Gilberto, Parker, Stephanie L., Balasubramanian, Sreeram, Davis, Nicholas S., Meadows, Sarah K., Eggleston, Tracy, Newberry, J. Scott, Levy, Shawn E., Absher, Devin M., Wong, Wing H., Blow, Matthew J., Visel, Axel, Pennachio, Len A., Petrykowska, Hanna M., Abyzov, Alexej, Aken, Bronwen, Barrell, Daniel, Barson, Gemma, Berry, Andrew, Bignell, Alexandra, Boychenko, Veronika, Bussotti, Giovanni, Davidson, Claire, Despacio-Reyes, Gloria, Diekhans, Mark, Ezkurdia, Iakes, Frankish, Adam, Gilbert, James, Gonzalez, Jose Manuel, Griffiths, Ed, Harte, Rachel, Hendrix, David A., Hunt, Toby, Jungreis, Irwin, Kay, Mike, Khurana, Ekta, Leng, Jing, Lin, Michael F., Loveland, Jane, Lu, Zhi, Manthravadi, Deepa, Mariotti, Marco, Mudge, Jonathan, Mukherjee, Gaurab, Notredame, Cedric, Pei, Baikang, Rodriguez, Jose Manuel, Saunders, Gary, Sboner, Andrea, Searle, Stephen, Sisu, Cristina, Snow, Catherine, Steward, Charlie, Tapanari, Electra, Tress, Michael L., van Baren, Marijke J., Washietl, Stefan, Wilming, Laurens, Zadissa, Amonida, Zhang, Zhengdong, Brent, Michael, Haussler, David, Valencia, Alfonso, Addleman, Nick, Alexander, Roger P., Auerbach, Raymond K., Balasubramanian, Suganthi, Bettinger, Keith, Bhardwaj, Nitin, Boyle, Alan P., Cao, Alina R., Cayting, Philip, Charos, Alexandra, Cheng, Yong, Eastman, Catharine, Euskirchen, Ghia, Fleming, Joseph D., Grubert, Fabian, Habegger, Lukas, Hariharan, Manoj, Harmanci, Arif, Iyengar, Sushma, Jin, Victor X., Karczewski, Konrad J., Kasowski, Maya, Lacroute, Phil, Lam, Hugo, Lamarre-Vincent, Nathan, Lian, Jin, Lindahl-Allen, Marianne, Min, Renqiang, Miotto, Benoit, Monahan, Hannah, Moqtaderi, Zarmik, Mu, Xinmeng J., Ouyang, Zhengqing, Patacsil, Dorrelyn, Raha, Debasish, Ramirez, Lucia, Reed, Brian, Shi, Minyi, Slifer, Teri, Witt, Heather, Wu, Linfeng, Xu, Xiaoqin, Yan, Koon-Kiu, Yang, Xinqiong, Struhl, Kevin, Weissman, Sherman M., Penalva, Luiz O., Karmakar, Subhradip, Bhanvadia, Raj R., Choudhury, Alina, Domanus, Marc, Ma, Lijia, Moran, Jennifer, Victorsen, Alec, Auer, Thomas, Centanin, Lazaro, Eichenlaub, Michael, Gruhl, Franziska, Heermann, Stephan, Hoeckendorf, Burkhard, Inoue, Daigo, Kellner, Tanja, Kirchmaier, Stephan, Mueller, Claudia, Reinhardt, Robert, Schertel, Lea, Schneider, Stephanie, Sinn, Rebecca, Wittbrodt, Beate, Wittbrodt, Jochen, Partridge, E. Christopher, Jain, Gaurav, Balasundaram, Gayathri, Bates, Daniel L., Byron, Rachel, Canfield, Theresa K., Diegel, Morgan J., Dunn, Douglas, Ebersol, Abigail K., Frum, Tristan, Garg, Kavita, Gist, Erica, Hansen, R. Scott, Boatman, Lisa, Haugen, Eric, Humbert, Richard, Johnson, Audra K., Johnson, Ericka M., Kutyavin, Tattyana V., Lee, Kristen, Lotakis, Dimitra, Maurano, Matthew T., Neph, Shane J., Neri, Fiedencio V., Nguyen, Eric D., Qu, Hongzhu, Reynolds, Alex P., Roach, Vaughn, Rynes, Eric, Sanchez, Minerva E., Sandstrom, Richard S., Shafer, Anthony O., Stergachis, Andrew B., Thomas, Sean, Vernot, Benjamin, Vierstra, Jeff, Vong, Shinny, Weaver, Molly A., Yan, Yongqi, Zhang, Miaohua, Akey, Joshua M., Bender, Michael, Dorschner, Michael O., Groudine, Mark, MacCoss, Michael J., Navas, Patrick, Stamatoyannopoulos, George, Beal, Kathryn, Brazma, Alvis, Flicek, Paul, Johnson, Nathan, Lukk, Margus, Luscombe, Nicholas M., Sobral, Daniel, Vaquerizas, Juan M., Batzoglou, Serafim, Sidow, Arend, Hussami, Nadine, Kyriazopoulou-Panagiotopoulou, Sofia, Libbrecht, Max W., Schaub, Marc A., Miller, Webb, Bickel, Peter J., Banfai, Balazs, Boley, Nathan P., Huang, Haiyan, Li, Jingyi Jessica, Noble, William Stafford, Bilmes, Jeffrey A., Buske, Orion J., Sahu, Avinash D., Kharchenko, Peter V., Park, Peter J., Baker, Dannon, Taylor, James, and Lochovsky, Lucas

Subjects
Research, Genetic research, Transcription (Genetics) -- Research, Human genome -- Research, Genetic transcription -- Research
Abstract

Author(s): The ENCODE Project Consortium; Overall coordination (data analysis coordination); Ian Dunham [2]; Anshul Kundaje [3, 82]; Data production leads (data production); Shelley F. Aldred [4]; Patrick J. Collins [4]; [...], The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Published
2012
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6. Phylogeography of Francisella tularensis: global expansion of a highly fit clone

Author

Vogler, Amy J., Birdsell, Dawn, Price, Lance B., Bowers, Jolene R., Beckstrom-Sternberg, Stephen M., Auerbach, Raymond K., Beckstrom-Sternberg, James S., Johansson, Anders, Clare, Ashley, Buchhagen, Jordan L., Petersen, Jeannine M., Pearson, Talima, Vaissaire, Josee, Dempsey, Michael P., Foxall, Paul, Engelthaler, David M., Wagner, David M., and Keim, Paul

Subjects
Francisella tularensis -- Genetic aspects, Phylogeny -- Research, Biological sciences
Abstract

Francisella tularensis contains several highly pathogenic subspecies, including Francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. The phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (SNP) analysis, high-density microarray SNP genotyping, and real-time-PCR-based canonical SNP (canSNP) assays. Almost 30,000 SNPs were identified among 13 whole genomes for phylogenetic analysis. We selected 1,655 SNPs to genotype 95 isolates on a high-density microarray platform. Finally, 23 clade- and subclade-specific canSNPs were identified and used to genotype 496 isolates to establish global geographic genetic patterns. We confirm previous findings concerning the four subspecies and two Francisella tularensis subsp. tularensis subpopulations and identify additional structure within these groups. We identify 11 subclades within F. tularensis subsp. holarctica, including a new, genetically distinct subclade that appears intermediate between Japanese F. tularensis subsp. holarctica isolates and the common F. tularensis subsp. holarctica isolates associated with the radiation event (the B radiation) wherein this subspecies spread throughout the northern hemisphere. Phylogenetic analyses suggest a North American origin for this B-radiation clade and multiple dispersal events between North America and Eurasia. These findings indicate a complex transmission history for F. tularensis subsp. holarctica.

Published
2009

7. A horizontal gene transfer event defines two distinct groups within Burkholderia pseudomallei that have dissimilar geographic distributions

Author

Tuanyok, Apichai, Auerbach, Raymond K., Brettin, Thomas S., Bruce, David C., Munk, A. Christine, Detter, J. Chris, Pearson, Talima, Hornstra, Heidie, Sermswan, Rasana W., Wuthiekanun, Vanaporn, Peacock, Sharon J., Currie, Bart J., Keim, Paul, and Wagner, David M.

Subjects
Bacterial genetics -- Research, Gram-negative bacteria -- Genetic aspects, Gram-negative bacteria -- Distribution, Gram-negative bacteria -- Varieties, Genetic transformation -- Research, Company distribution practices, Biological sciences
Abstract

Burkholderia pseudomallei is the etiologic agent of melioidosis. Many disease manifestations are associated with melioidosis, and the mechanisms causing this variation are unknown; genomic differences among strains offer one explanation. We compared the genome sequences of two strains of B. pseudomallei: the original reference strain K96243 from Thailand and strain MSHR305 from Australia. We identified a variable homologous region between the two strains. This region was previously identified in comparisons of the genome of B. pseudomallei strain K96243 with the genome of strain E264 from the closely related B. thailandensis. In that comparison, K96243 was shown to possess a horizontally acquired Yersinia-like fimbrial (YLF) gene cluster. Here, we show that the homologous genomic region in B. pseudomallei strain 305 is similar to that previously identified in B. thailandensis strain E264. We have named this region in B. pseudomallei strain 305 the B. thailandensis-like flagellum and chemotaxis (BTFC) gene cluster. We screened for these different genomic components across additional genome sequences and 571 B. pseudomallei DNA extracts obtained from regions of endemicity. These alternate genomic states define two distinct groups within B. pseudomallei: all strains contained either the BTFC gene cluster (group BTFC) or the YLF gene cluster (group YLF). These two groups have distinct geographic distributions: group BTFC is dominant in Australia, and group YLF is dominant in Thailand and elsewhere. In addition, clinical isolates are more likely to belong to group YLF, whereas environmental isolates are more likely to belong to group BTFC. These groups should be further characterized in an animal model.

Published
2007

8. Phenotypic and functional characterization of Bacillus anthracis biofilms

Author

Lee, Keehoon, Costerton, J.W., Ravel, Jacques, Auerbach, Raymond K., Wagner, David M., Keim, Paul, and Leid, Jeff G.

Subjects
Bacillus anthracis -- Research, Bacillus anthracis -- Health aspects, Microbial mats -- Health aspects, Microbial mats -- Research, Phenotype -- Research, Drug resistance in microorganisms -- Research, Biological sciences
Abstract

Biofilms, communities of micro-organisms attached to a surface, are responsible for many chronic diseases and are often associated with environmental reservoirs or lifestyles. Bacillus anthracis is a Gram-positive, endospore-forming bacterium and is the aetiological agent of pulmonary, gastrointestinal and cutaneous anthrax. Anthrax infections are part of the natural lifecycle of many ruminants in North America, including cattle and bison, and B. anthracis is thought to be a central part of this ecosystem. However, in endemic areas in which humans and livestock interact, chronic cases of cutaneous anthrax are commonly reported. This suggests that biofilms of B. anthracis exist in the environment and are part of the ecology associated with its lifecycle. Currently, there are few data that account for the importance of the biofilm mode of life in B. anthracis, yet biofilms have been characterized in other pathogenic and non-pathogenic Bacillus species, including Bacillus cereus and Bacillus subtilis, respectively. This study investigated the phenotypic and functional role of biofilms in B. anthracis. The results demonstrate that B. anthracis readily forms biofilms which are inherently resistant to commonly prescribed antibiotics, and that antibiotic resistance is not solely the function of sporulation.

Published
2007

10. Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project

Author

Gerstein, Mark B., Lu, Zhi John, Van Nostrand, Eric L., Cheng, Chao, Arshinoff, Bradley I., Liu, Tao, Yip, Kevin Y., Robilotto, Rebecca, Rechtsteiner, Andreas, Ikegami, Kohta, Alves, Pedro, Chateigner, Aurelien, Perry, Marc, Morris, Mitzi, Auerbach, Raymond K., Feng, Xin, Leng, Jing, Vielle, Anne, Niu, Wei, Rhrissorrakrai, Kahn, Agarwal, Ashish, Alexander, Roger P., Barber, Galt, Brdlik, Cathleen M., Brennan, Jennifer, Brouillet, Jeremy Jean, Carr, Adrian, Cheung, Ming-Sin, Clawson, Hiram, Contrino, Sergio, Dannenberg, Luke O., Dernburg, Abby F., Desai, Arshad, Dick, Lindsay, Dosé, Andréa C., Du, Jiang, Egelhofer, Thea, Ercan, Sevinc, Euskirchen, Ghia, Ewing, Brent, Feingold, Elise A., Gassmann, Reto, Good, Peter J., Green, Phil, Gullier, Francois, Gutwein, Michelle, Guyer, Mark S., Habegger, Lukas, Han, Ting, Henikoff, Jorja G., Henz, Stefan R., Hinrichs, Angie, Holster, Heather, Hyman, Tony, Iniguez, Leo A., Janette, Judith, Jensen, Morten, Kato, Masaomi, Kent, James W., Kephart, Ellen, Khivansara, Vishal, Khurana, Ekta, Kim, John K., Kolasinska-Zwierz, Paulina, Lai, Eric C., Latorre, Isabel, Leahey, Amber, Lewis, Suzanna, Lloyd, Paul, Lochovsky, Lucas, Lowdon, Rebecca F., Lubling, Yaniv, Lyne, Rachel, MacCoss, Michael, Mackowiak, Sebastian D., Mangone, Marco, McKay, Sheldon, Mecenas, Desirea, Merrihew, Gennifer, Miller, David M., III, Muroyama, Andrew, Murray, John I., Ooi, Siew-Loon, Pham, Hoang, Phippen, Taryn, Preston, Elicia A., Rajewsky, Nikolaus, Rätsch, Gunnar, Rosenbaum, Heidi, Rozowsky, Joel, Rutherford, Kim, Ruzanov, Peter, Sarov, Mihail, Sasidharan, Rajkumar, Sboner, Andrea, Scheid, Paul, Segal, Eran, Shin, Hyunjin, Shou, Chong, Slack, Frank J., Slightam, Cindie, Smith, Richard, Spencer, William C., Stinson, E. O., Taing, Scott, Takasaki, Teruaki, Vafeados, Dionne, Voronina, Ksenia, Wang, Guilin, Washington, Nicole L., Whittle, Christina M., Wu, Beijing, Yan, Koon-Kiu, Zeller, Georg, Zha, Zheng, Zhong, Mei, Zhou, Xingliang, Ahringer, Julie, Strome, Susan, Gunsalus, Kristin C., Micklem, Gos, Liu, Shirley X., Reinke, Valerie, Kim, Stuart K., Hillier, LaDeana W., Henikoff, Steven, Piano, Fabio, Snyder, Michael, Stein, Lincoln, Lieb, Jason D., and Waterston, Robert H.

Published
2010
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12. Francisella tularensis subsp. novicida isolated from a human in Arizona

Author

Birdsell Dawn N, Stewart Tasha, Vogler Amy J, Lawaczeck Elisabeth, Diggs Alisa, Sylvester Tammy L, Buchhagen Jordan L, Auerbach Raymond K, Keim Paul, and Wagner David M

Subjects
Medicine, Biology (General), QH301-705.5, Science (General), Q1-390
Abstract

Abstract Background Francisella tularensis is the etiologic agent of tularemia and is classified as a select agent by the Centers for Disease Control and Prevention. Currently four known subspecies of F. tularensis that differ in virulence and geographical distribution are recognized:tularensis (type A), holarctica (type B), mediasiatica, and novicida. Because of the Select Agent status and differences in virulence and geographical location, the molecular analysis of any clinical case of tularemia is of particular interest. We analyzed an unusual Francisella clinical isolate from a human infection in Arizona using multiple DNA-based approaches. Findings We report that the isolate is F. tularensis subsp. novicida, a subspecies that is rarely isolated. Conclusion The rarity of this novicida subspecies in clinical settings makes each case study important for our understanding of its role in disease and its genetic relationship with other F. tularensis subspecies.

Published
2009
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13. Efficient yeast ChIP-Seq using multiplex short-read DNA sequencing

Author

Yellman Christopher M, Gibson Theodore, Rozowsky Joel, Auerbach Raymond K, Euskirchen Ghia M, Lefrançois Philippe, Gerstein Mark, and Snyder Michael

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Short-read high-throughput DNA sequencing technologies provide new tools to answer biological questions. However, high cost and low throughput limit their widespread use, particularly in organisms with smaller genomes such as S. cerevisiae. Although ChIP-Seq in mammalian cell lines is replacing array-based ChIP-chip as the standard for transcription factor binding studies, ChIP-Seq in yeast is still underutilized compared to ChIP-chip. We developed a multiplex barcoding system that allows simultaneous sequencing and analysis of multiple samples using Illumina's platform. We applied this method to analyze the chromosomal distributions of three yeast DNA binding proteins (Ste12, Cse4 and RNA PolII) and a reference sample (input DNA) in a single experiment and demonstrate its utility for rapid and accurate results at reduced costs. Results We developed a barcoding ChIP-Seq method for the concurrent analysis of transcription factor binding sites in yeast. Our multiplex strategy generated high quality data that was indistinguishable from data obtained with non-barcoded libraries. None of the barcoded adapters induced differences relative to a non-barcoded adapter when applied to the same DNA sample. We used this method to map the binding sites for Cse4, Ste12 and Pol II throughout the yeast genome and we found 148 binding targets for Cse4, 823 targets for Ste12 and 2508 targets for PolII. Cse4 was strongly bound to all yeast centromeres as expected and the remaining non-centromeric targets correspond to highly expressed genes in rich media. The presence of Cse4 non-centromeric binding sites was not reported previously. Conclusion We designed a multiplex short-read DNA sequencing method to perform efficient ChIP-Seq in yeast and other small genome model organisms. This method produces accurate results with higher throughput and reduced cost. Given constant improvements in high-throughput sequencing technologies, increasing multiplexing will be possible to further decrease costs per sample and to accelerate the completion of large consortium projects such as modENCODE.

Published
2009
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14. Genomic islands from five strains of Burkholderia pseudomallei

Author

Nierman William C, Brettin Thomas S, Wuthiekanun Vanaporn, Mayo Mark, Beckstrom-Sternberg James S, Beckstrom-Sternberg Stephen M, Auerbach Raymond K, Leadem Benjamin R, Tuanyok Apichai, Peacock Sharon J, Currie Bart J, Wagner David M, and Keim Paul

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Burkholderia pseudomallei is the etiologic agent of melioidosis, a significant cause of morbidity and mortality where this infection is endemic. Genomic differences among strains of B. pseudomallei are predicted to be one of the major causes of the diverse clinical manifestations observed among patients with melioidosis. The purpose of this study was to examine the role of genomic islands (GIs) as sources of genomic diversity in this species. Results We found that genomic islands (GIs) vary greatly among B. pseudomallei strains. We identified 71 distinct GIs from the genome sequences of five reference strains of B. pseudomallei: K96243, 1710b, 1106a, MSHR668, and MSHR305. The genomic positions of these GIs are not random, as many of them are associated with tRNA gene loci. In particular, the 3' end sequences of tRNA genes are predicted to be involved in the integration of GIs. We propose the term "tRNA-mediated site-specific recombination" (tRNA-SSR) for this mechanism. In addition, we provide a GI nomenclature that is based upon integration hotspots identified here or previously described. Conclusion Our data suggest that acquisition of GIs is one of the major sources of genomic diversity within B. pseudomallei and the molecular mechanisms that facilitate horizontally-acquired GIs are common across multiple strains of B. pseudomallei. The differential presence of the 71 GIs across multiple strains demonstrates the importance of these mobile elements for shaping the genetic composition of individual strains and populations within this bacterial species.

Published
2008
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15. The In Silico Genotyper (ISG): an open-source pipeline to rapidly identify and annotate nucleotide variants for comparative genomics applications

Author

Sahl, Jason W, primary, Beckstrom-Sternberg, Stephen M, additional, Babic-Sternberg, James, additional, Gillece, John D, additional, Hepp, Crystal M, additional, Auerbach, Raymond K, additional, Tembe, Waibhav, additional, Wagner, David M, additional, Keim, Paul S, additional, and Pearson, Talima, additional

Published
2015
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16. Phylogeography of Francisella tularensis : global expansion of a highly fit clone

Author

Vogler, Amy J, Birdsell, Dawn, Price, Lance B, Bowers, Jolene R, Beckstrom-Sternberg, Stephen M, Auerbach, Raymond K, Beckstrom-Sternberg, James S, Johansson, Anders, Clare, Ashley, Buchhagen, Jordan L, Petersen, Jeannine M, Pearson, Talima, Vaissaire, Josée, Dempsey, Michael P, Foxall, Paul, Engelthaler, David M, Wagner, David M, Keim, Paul, Vogler, Amy J, Birdsell, Dawn, Price, Lance B, Bowers, Jolene R, Beckstrom-Sternberg, Stephen M, Auerbach, Raymond K, Beckstrom-Sternberg, James S, Johansson, Anders, Clare, Ashley, Buchhagen, Jordan L, Petersen, Jeannine M, Pearson, Talima, Vaissaire, Josée, Dempsey, Michael P, Foxall, Paul, Engelthaler, David M, Wagner, David M, and Keim, Paul

Abstract

Francisella tularensis contains several highly pathogenic subspecies, including Francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. The phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (SNP) analysis, high-density microarray SNP genotyping, and real-time-PCR-based canonical SNP (canSNP) assays. Almost 30,000 SNPs were identified among 13 whole genomes for phylogenetic analysis. We selected 1,655 SNPs to genotype 95 isolates on a high-density microarray platform. Finally, 23 clade- and subclade-specific canSNPs were identified and used to genotype 496 isolates to establish global geographic genetic patterns. We confirm previous findings concerning the four subspecies and two Francisella tularensis subsp. tularensis subpopulations and identify additional structure within these groups. We identify 11 subclades within F. tularensis subsp. holarctica, including a new, genetically distinct subclade that appears intermediate between Japanese F. tularensis subsp. holarctica isolates and the common F. tularensis subsp. holarctica isolates associated with the radiation event (the B radiation) wherein this subspecies spread throughout the northern hemisphere. Phylogenetic analyses suggest a North American origin for this B-radiation clade and multiple dispersal events between North America and Eurasia. These findings indicate a complex transmission history for F. tularensis subsp. holarctica.

Published
2009
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17. Genomic islands from five strains of Burkholderia pseudomallei

Author

Tuanyok, Apichai, Leadem, Benjamin R., Auerbach, Raymond K., Beckstrom-Sternberg, Stephen M., Beckstrom-Sternberg, James S., Mayo, Mark J., Wuthiekanun, Vanaporn, Brettin, Thomas S., Nierman, William C., Peacock, Sharon J., Currie, Bart J., Wagner, David M., Keim, Paul, Tuanyok, Apichai, Leadem, Benjamin R., Auerbach, Raymond K., Beckstrom-Sternberg, Stephen M., Beckstrom-Sternberg, James S., Mayo, Mark J., Wuthiekanun, Vanaporn, Brettin, Thomas S., Nierman, William C., Peacock, Sharon J., Currie, Bart J., Wagner, David M., and Keim, Paul

Abstract

Background: Burkholderia pseudomallei is the etiologic agent of melioidosis, a significant cause of morbidity and mortality where this infection is endemic. Genomic differences among strains of B. pseudomallei are predicted to be one of the major causes of the diverse clinical manifestations observed among patients with melioidosis. The purpose of this study was to examine the role of genomic islands (GIs) as sources of genomic diversity in this species.Results: We found that genomic islands (GIs) vary greatly among B. pseudomallei strains. We identified 71 distinct GIs from the genome sequences of five reference strains of B. pseudomallei: K96243, 1710b, 1106a, MSHR668, and MSHR305. The genomic positions of these GIs are not random, as many of them are associated with tRNA gene loci. In particular, the 3' end sequences of tRNA genes are predicted to be involved in the integration of GIs. We propose the term "tRNAmediated site-specific recombination" (tRNA-SSR) for this mechanism. In addition, we provide a GI nomenclature that is based upon integration hotspots identified here or previously described.Conclusion: Our data suggest that acquisition of GIs is one of the major sources of genomic diversity within B. pseudomallei and the molecular mechanisms that facilitate horizontally-acquired GIs are common across multiple strains of B. pseudomallei. The differential presence of the 71 GIs across multiple strains demonstrates the importance of these mobile elements for shaping the genetic composition of individual strains and populations within this bacterial species.

Published
2008

19. Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

Author

Li, Guoliang, primary, Ruan, Xiaoan, additional, Auerbach, Raymond K., additional, Sandhu, Kuljeet Singh, additional, Zheng, Meizhen, additional, Wang, Ping, additional, Poh, Huay Mei, additional, Goh, Yufen, additional, Lim, Joanne, additional, Zhang, Jingyao, additional, Sim, Hui Shan, additional, Peh, Su Qin, additional, Mulawadi, Fabianus Hendriyan, additional, Ong, Chin Thing, additional, Orlov, Yuriy L., additional, Hong, Shuzhen, additional, Zhang, Zhizhuo, additional, Landt, Steve, additional, Raha, Debasish, additional, Euskirchen, Ghia, additional, Wei, Chia-Lin, additional, Ge, Weihong, additional, Wang, Huaien, additional, Davis, Carrie, additional, Fisher-Aylor, Katherine I., additional, Mortazavi, Ali, additional, Gerstein, Mark, additional, Gingeras, Thomas, additional, Wold, Barbara, additional, Sun, Yi, additional, Fullwood, Melissa J., additional, Cheung, Edwin, additional, Liu, Edison, additional, Sung, Wing-Kin, additional, Snyder, Michael, additional, and Ruan, Yijun, additional

Published
2012
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24. Genomic islands from five strains of Burkholderia pseudomallei

Author

Tuanyok, Apichai, primary, Leadem, Benjamin R, additional, Auerbach, Raymond K, additional, Beckstrom-Sternberg, Stephen M, additional, Beckstrom-Sternberg, James S, additional, Mayo, Mark, additional, Wuthiekanun, Vanaporn, additional, Brettin, Thomas S, additional, Nierman, William C, additional, Peacock, Sharon J, additional, Currie, Bart J, additional, Wagner, David M, additional, and Keim, Paul, additional

Published
2008
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25. Assays for the rapid and specific identification of North American Yersinia pestis and the common laboratory strain CO92

Author

Vogler, Amy J., primary, Driebe, Elizabeth M., additional, Lee, Judy, additional, Auerbach, Raymond K., additional, Allender, Christopher J., additional, Stanley, Miles, additional, Kubota, Kristy, additional, Andersen, Gary L., additional, Radnedge, Lyndsay, additional, Worsham, Patricia L., additional, Keim, Paul, additional, and Wagner, David M., additional

Published
2008
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26. Complete Genomic Characterization of a Pathogenic A.II Strain of Francisella tularensis Subspecies tularensis

Author

Beckstrom-Sternberg, Stephen M., primary, Auerbach, Raymond K., additional, Godbole, Shubhada, additional, Pearson, John V., additional, Beckstrom-Sternberg, James S., additional, Deng, Zuoming, additional, Munk, Christine, additional, Kubota, Kristy, additional, Zhou, Yan, additional, Bruce, David, additional, Noronha, Jyothi, additional, Scheuermann, Richard H., additional, Wang, Aihui, additional, Wei, Xianying, additional, Wang, Jianjun, additional, Hao, Jicheng, additional, Wagner, David M., additional, Brettin, Thomas S., additional, Brown, Nancy, additional, Gilna, Paul, additional, and Keim, Paul S., additional

Published
2007
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27. Yersinia pestis Evolution on a Small Timescale: Comparison of Whole Genome Sequences from North America

Author

Auerbach, Raymond K., primary, Tuanyok, Apichai, additional, Probert, William S., additional, Kenefic, Leo, additional, Vogler, Amy J., additional, Bruce, David C., additional, Munk, Christine, additional, Brettin, Thomas S., additional, Eppinger, Mark, additional, Ravel, Jacques, additional, Wagner, David M., additional, and Keim, Paul, additional

Published
2007
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28. A North American Yersinia pestis Draft Genome Sequence: SNPs and Phylogenetic Analysis

Author

Touchman, Jeffrey W., primary, Wagner, David M., additional, Hao, Jicheng, additional, Mastrian, Stephen D., additional, Shah, Maulik K., additional, Vogler, Amy J., additional, Allender, Christopher J., additional, Clark, Erin A., additional, Benitez, Debbie S., additional, Youngkin, David J., additional, Girard, Jessica M., additional, Auerbach, Raymond K., additional, Beckstrom-Sternberg, Stephen M., additional, and Keim, Paul, additional

Published
2007
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29. Assays for the rapid and specific identification of North American Yersinia pestisand the common laboratory strain CO92

Author

Vogler, Amy J., Driebe, Elizabeth M., Lee, Judy, Auerbach, Raymond K., Allender, Christopher J., Stanley, Miles, Kubota, Kristy, Andersen, Gary L., Radnedge, Lyndsay, Worsham, Patricia L., Keim, Paul, and Wagner, David M.

Abstract

We present TaqMan-minor groove binding (MGB) assays for an SNP that separates the Yersinia pestis strain CO92 from all other strains and for another SNP that separates North American strains from all other global strains.

Published
2008
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30. Phenotypic and functional characterization of Bacillus anthracis biofilms.

Author

Keehoon Lee, Costerton, J. W., Ravel, Jacques, Auerbach, Raymond K., Wagner, David M., Keim, Paul, and Leid, Jeff G.

Subjects
*MICROBIOLOGY, *BACILLUS anthracis, *BIOFILMS, *BACILLUS (Bacteria), *PATHOGENIC microorganisms, *ANTHRAX, *BACTERIAL diseases
Abstract

The article presents microbiological research into Bacillus anthracis biofilms, or surface-attached communities of microorganisms that are responsible for chronic diseases. This Gram-positive endospore-forming bacterium is the aetiological agent of cutaneous, pulmonary, and gastrointestinal anthrax. Results indicate Bacillus anthracis biofilms are resistant to antiobiotics.

Published
2007
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31. Thriving in multidisciplinary research: advice for new bioinformatics students.

Author

Auerbach RK

Subjects
Algorithms, Computational Biology methods, Humans, Learning, Publishing standards, Workforce, Biomedical Engineering education, Computational Biology education, Interdisciplinary Communication, Students
Abstract

The sciences have seen a large increase in demand for students in bioinformatics and multidisciplinary fields in general. Many new educational programs have been created to satisfy this demand, but navigating these programs requires a non-traditional outlook and emphasizes working in teams of individuals with distinct yet complementary skill sets. Written from the perspective of a current bioinformatics student, this article seeks to offer advice to prospective and current students in bioinformatics regarding what to expect in their educational program, how multidisciplinary fields differ from more traditional paths, and decisions that they will face on the road to becoming successful, productive bioinformaticists.

Published
2012

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