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22 results on '"Maskeri, Baishali"'

1. A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope

Author

Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shiling, Legaspi, Richelle, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Mullikin, James, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, Young, Alice, Zhou, Tongqing, Zheng, Anqi, Baxa, Ulrich, Chuang, Gwo-Yu, Georgiev, Ivelin S., Kong, Rui, O’Dell, Sijy, Shahzad-ul-Hussan, Syed, Shen, Chen-Hsiang, Tsybovsky, Yaroslav, Bailer, Robert T., Gift, Syna K., Louder, Mark K., McKee, Krisha, Rawi, Reda, Stevenson, Catherine H., Stewart-Jones, Guillaume B.E., Taft, Justin D., Waltari, Eric, Yang, Yongping, Zhang, Baoshan, Shivatare, Sachin S., Shivatare, Vidya S., Lee, Chang-Chun D., Wu, Chung-Yi, Mullikin, James C., Bewley, Carole A., Burton, Dennis R., Polonis, Victoria R., Shapiro, Lawrence, Wong, Chi-Huey, Mascola, John R., Kwong, Peter D., and Wu, Xueling

Published
2018
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2. Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma

Author

Gartner, Jared J, Parker, Stephen CJ, Prickett, Todd D, Dutton-Regester, Ken, Stitzel, Michael L, Lin, Jimmy C, Davis, Sean, Simhadri, Vijaya L, Jha, Sujata, Katagiri, Nobuko, Gotea, Valer, Teer, Jamie K, Wei, Xiaomu, Morken, Mario A, Bhanot, Umesh K, Chen, Guo, Elnitski, Laura L, Davies, Michael A, Gershenwald, Jeffrey E, Carter, Hannah, Karchin, Rachel, Robinson, William, Robinson, Steven, Rosenberg, Steven A, Collins, Francis S, Parmigiani, Giovanni, Komar, Anton A, Kimchi-Sarfaty, Chava, Hayward, Nicholas K, Margulies, Elliott H, Samuels, Yardena, Becker, Jesse, Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Johnson, Taccara, Legaspi, Richelle, Lovett, Sean, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Mullikin, James, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, and Young, Alice

Subjects
Biotechnology, Human Genome, Genetics, Cancer, Prevention, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Aetiology, Generic health relevance, Apoptosis, Base Sequence, Blotting, Western, DNA Primers, Exome, Gene Expression Regulation, Genetic Vectors, Genome, Human, HEK293 Cells, Humans, Immunoprecipitation, Lentivirus, Melanoma, MicroRNAs, Molecular Sequence Data, Muscle Proteins, Mutation, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-bcl-2, RNA, Small Interfering, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA, Tumor Suppressor Protein p53, NISC Comparative Sequencing Program
Abstract

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671-5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies.

Published
2013

3. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection

Author

Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, Young, Alice, Wu, Xueling, Zhang, Zhenhai, Schramm, Chaim A., Joyce, M. Gordon, Do Kwon, Young, Zhou, Tongqing, Sheng, Zizhang, Zhang, Baoshan, O’Dell, Sijy, McKee, Krisha, Georgiev, Ivelin S., Chuang, Gwo-Yu, Longo, Nancy S., Lynch, Rebecca M., Saunders, Kevin O., Soto, Cinque, Srivatsan, Sanjay, Yang, Yongping, Bailer, Robert T., Louder, Mark K., Mullikin, James C., Connors, Mark, Kwong, Peter D., Mascola, John R., and Shapiro, Lawrence

Published
2015
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4. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease

Author

Kirino, Yohei, Zhou, Qing, Ishigatsubo, Yoshiaki, Mizuki, Nobuhisa, Tugal-Tutkun, Ilknur, Seyahi, Emire, Özyazgan, Yilmaz, Ugurlu, Serdal, Erer, Burak, Abaci, Neslihan, Ustek, Duran, Meguro, Akira, Ueda, Atsuhisa, Takeno, Mitsuhiro, Inoko, Hidetoshi, Ombrello, Michael J., Satorius, Colleen L., Maskeri, Baishali, Mullikin, James C., Sun, Hong-Wei, Gutierrez-Cruz, Gustavo, Kim, Yoonhee, Wilson, Alexander F., Kastner, Daniel L., Gül, Ahmet, and Remmers, Elaine F.

Published
2013

5. Biogeography and individuality shape function in the human skin metagenome

Author

Oh, Julia, Byrd, Allyson L., Deming, Clay, Conlan, Sean, Barnabas, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Ho, Shi-ling, Legaspi, Richelle, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Mullikin, James, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pamela, Vemulapalli, Meg, Young, Alice, Kong, Heidi H., and Segre, Julia A.

Published
2014
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6. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project

Author

Birney, Ewan, Stamatoyannopoulos, John A., Dutta, Anindya, Guigo, Roderic, Gingeras, Thomas R., Margulies, Elliott H., Weng, Zhiping, Snyder, Michael, Dermitzakis, Emmanouil T., Thurman, Robert E., Kuehn, Michael S., Taylor, Christopher M., Neph, Shane, Koch, Christoph M., Asthana, Saurabh, Malhotra, Ankit, Adzhubei, Ivan, Greenbaum, Jason A., Andrews, Robert M., Flicek, Paul, Boyle, Patrick J., Cao, Hua, Carter, Nigel P., Clelland, Gayle K., Davis, Sean, Day, Nathan, Dhami, Pawandeep, Dillon, Shane C., Dorschner, Michael O., Fiegler, Heike, Giresi, Paul G., Goldy, Jeff, Hawrylycz, Michael, Haydock, Andrew, Humbert, Richard, James, Keith D., Johnson, Brett E., Johnson, Ericka M., Frum, Tristan T., Rosenzweig, Elizabeth R., Karnani, Neerja, Lee, Kirsten, Lefebvre, Gregory C., Navas, Patrick A., Neri, Fidencio, Parker, Stephen C. J., Sabo, Peter J., Sandstrom, Richard, Shafer, Anthony, Vetrie, David, Weaver, Molly, Wilcox, Sarah, Yu1, Man, Collins, Francis S., Dekker, Job, Lieb, Jason D., Tullius, Thomas D., Crawford, Gregory E., Sunyaev, Shamil, Noble, William S., Dunham, Ian, Denoeud, France, Reymond, Alexandre, Kapranov, Philipp, Rozowsky, Joel, Zheng, Deyou, Castelo, Robert, Frankish, Adam, Harrow, Jennifer, Ghosh, Srinka, Sandelin, Albin, Hofacker, Ivo L., Baertsch, Robert, Keefe, Damian, Dike, Sujit, Cheng, Jill, Hirsch, Heather A., Sekinger, Edward A., Lagarde, Julien, Abril, Josep F., Shahab, Atif, Flamm, Christoph, Fried, Claudia, Hackermuller, Jorg, Hertel, Jana, Lindemeyer, Manja, Missal, Kristin, Tanzer, Andrea, Washietl, Stefan, Korbel, Jan, Emanuelsson, Olof, Pedersen, Jakob S., Holroyd, Nancy, Taylor, Ruth, Swarbreck, David, Matthews, Nicholas, Dickson, Mark C., Thomas, Daryl J., Weirauch, Matthew T., Gilbert, James, Drenkow, Jorg, Bell, Ian, Zhao, XiaoDong, Srinivasan, K.G., Sung, Wing-Kin, Ooi, Hong Sain, Chiu, Kuo Ping, Foissac, Sylvain, Alioto, Tyler, Brent, Michael, Pachter, Lior, Tress, Michael L., Valencia, Alfonso, Choo, Siew Woh, Choo, Chiou Yu, Ucla, Catherine, Manzano, Caroline, Wyss, Carine, Cheung, Evelyn, Clark, Taane G., Brown, James B., Ganesh, Madhavan, Patel, Sandeep, Tammana, Hari, Chrast, Jacqueline, Henrichsen, Charlotte N., Kai, Chikatoshi, Kawai, Jun, Nagalakshmi, Ugrappa, Wu, Jiaqian, Lian, Zheng, Lian, Jin, Newburger, Peter, Zhang, Xueqing, Bickel, Peter, Mattick, John S., Carninci, Piero, Hayashizaki, Yoshihide, Weissman, Sherman, Hubbard, Tim, Myers, Richard M., Rogers, Jane, Stadler, Peter F., Lowe, Todd M., Wei, Chia-Lin, Ruan, Yijun, Struhl, Kevin, Gerstein, Mark, Antonarakis, Stylianos E., Fu, Yutao, Green, Eric D., Karaoz, Ulaş, Siepel, Adam, Taylor, James, Liefer, Laura A., Wetterstrand, Kris A., Good, Peter J., Feingold, Elise A., Guyer, Mark S., Cooper, Gregory M., Asimenos, George, Dewey, Colin N., Hou, Minmei, Nikolaev, Sergey, Montoya-Burgos, Juan I., Loytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Huang, Haiyan, Zhang, Nancy R., Holmes, Ian, Mullikin, James C., Ureta-Vidal, Abel, Paten, Benedict, Seringhaus, Michael, Church, Deanna, Rosenbloom, Kate, Kent, W. James, Stone, Eric A., Batzoglou, Serafim, Goldman, Nick, Hardison, Ross C., Haussler, David, Miller, Webb, Sidow, Arend, Trinklein, Nathan D., Zhang, Zhengdong D., Barrera, Leah, Stuart, Rhona, King, David C., Ameur, Adam, Enroth, Stefan, Bieda, Mark C., Kim, Jonghwan, Bhinge, Akshay A., Jiang, Nan, Liu, Jun, Yao, Fei, Vega, Vinsensius B., Lee, Charlie W.H., Ng, Patrick, Yang, Annie, Moqtaderi, Zarmik, Zhu, Zhou, Xu, Xiaoqin, Squazzo, Sharon, Oberley, Matthew J., Inman, David, Singer, Michael A., Richmond, Todd A., Munn, Kyle J., Rada-Iglesias, Alvaro, Wallerman, Ola, Komorowski, Jan, Fowler, Joanna C., Couttet, Phillippe, Bruce, Alexander W., Dovey, Oliver M., Ellis, Peter D., Langford, Cordelia F., Nix, David A., Euskirchen, Ghia, Hartman, Stephen, Urban, Alexander E., Kraus, Peter, Van Calcar, Sara, Heintzman, Nate, Hoon Kim, Tae, Wang, Kun, Qu, Chunxu, Hon, Gary, Luna, Rosa, Glass, Christopher K., Rosenfeld, M. Geoff, Aldred, Shelley Force, Cooper, Sara J., Halees, Anason, Lin, Jane M., Shulha, Hennady P., Zhang, Xiaoling, Xu, Mousheng, Haidar, Jaafar N. S., Yu, Yong, Birney*, Ewan, Iyer, Vishwanath R., Green, Roland D., Wadelius, Claes, Farnham, Peggy J., Ren, Bing, Harte, Rachel A., Hinrichs, Angie S., Trumbower, Heather, Clawson, Hiram, Hillman-Jackson, Jennifer, Zweig, Ann S., Smith, Kayla, Thakkapallayil, Archana, Barber, Galt, Kuhn, Robert M., Karolchik, Donna, Armengol, Lluis, Bird, Christine P., de Bakker, Paul I. W., Kern, Andrew D., Lopez-Bigas, Nuria, Martin, Joel D., Stranger, Barbara E., Woodroffe, Abigail, Davydov, Eugene, Dimas, Antigone, Eyras, Eduardo, Hallgrimsdottir, Ingileif B., Huppert, Julian, Zody, Michael C., Abecasis, Goncalo R., Estivill, Xavier, Bouffard, Gerard G., Guan, Xiaobin, Hansen, Nancy F., Idol, Jacquelyn R., Maduro, Valerie V.B., Maskeri, Baishali, McDowell, Jennifer C., Park, Morgan, Thomas, Pamela J., Young, Alice C., Blakesley, Robert W., Baylor College of Medicine, Human Genome Sequencing Center, Muzny, Donna M., Sodergren, Erica, Wheeler, David A., Worley, Kim C., Jiang, Huaiyang, Weinstock, George M., Gibbs, Richard A., Graves, Tina, Fulton, Robert, Mardis, Elaine R., Wilson, Richard K., Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B., Chang, Jean L., Lindblad-Toh, Kerstin, Lander, Eric S., Koriabine, Maxim, Nefedov, Mikhail, Osoegawa, Kazutoyo, Yoshinaga, Yuko, Zhu, Baoli, and de Jong, Pieter J.

Abstract

Author(s): The ENCODE Project Consortium; Analysis Coordination; Ewan Birney (corresponding author) [1]; John A. Stamatoyannopoulos (corresponding author) [2]; Anindya Dutta (corresponding author) [3]; Roderic Guigó (corresponding author) [4, 5]; Thomas [...]

Published
2007
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7. Topographic diversity of fungal and bacterial communities in human skin

Author

Findley, Keisha, Oh, Julia, Yang, Joy, Conlan, Sean, Deming, Clayton, Meyer, Jennifer A., Schoenfeld, Deborah, Nomicos, Effie, Park, Morgan, Becker, Jesse, Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Johnson, Taccara, Legaspi, Richelle, Lovett, Sean, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Mullikin, James, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, Young, Alice, Kong, Heidi H., and Segre, Julia A.

Published
2013
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8. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

Author

Liao, Hua-Xin, Lynch, Rebecca, Zhou, Tongqing, Gao, Feng, Alam, S. Munir, Boyd, Scott D., Fire, Andrew Z., Roskin, Krishna M., Schramm, Chaim A., Zhang, Zhenhai, Zhu, Jiang, Shapiro, Lawrence, Becker, Jesse, Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Johnson, Taccara, Legaspi, Richelle, Lovett, Sean, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Mullikin, James, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, Young, Alice, Mullikin, James C., Gnanakaran, S., Hraber, Peter, Wiehe, Kevin, Kelsoe, Garnett, Yang, Guang, Xia, Shi-Mao, Montefiori, David C., Parks, Robert, Lloyd, Krissey E., Scearce, Richard M., Soderberg, Kelly A., Cohen, Myron, Kamanga, Gift, Louder, Mark K., Tran, Lillian M., Chen, Yue, Cai, Fangping, Chen, Sheri, Moquin, Stephanie, Du, Xiulian, Joyce, M. Gordon, Srivatsan, Sanjay, Zhang, Baoshan, Zheng, Anqi, Shaw, George M., Hahn, Beatrice H., Kepler, Thomas B., Korber, Bette T. M., Kwong, Peter D., Mascola, John R., and Haynes, Barton F.

Published
2013
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9. Effort required to finish shotgun-generated genome sequences differs significantly among vertebrates

Author

Stantripop Sirintorn, Schandler Karen, Ho Shi-Ling, Haghighi Payam, Coleman Holly, Barnabas Beatrice B, Brooks Shelise Y, Maskeri Baishali, McDowell Jennifer C, Gupta Jyoti, Hansen Nancy F, Blakesley Robert W, Vogt Jennifer L, Thomas Pamela J, Bouffard Gerard G, and Green Eric D

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

Abstract Background The approaches for shotgun-based sequencing of vertebrate genomes are now well-established, and have resulted in the generation of numerous draft whole-genome sequence assemblies. In contrast, the process of refining those assemblies to improve contiguity and increase accuracy (known as 'sequence finishing') remains tedious, labor-intensive, and expensive. As a result, the vast majority of vertebrate genome sequences generated to date remain at a draft stage. Results To date, our genome sequencing efforts have focused on comparative studies of targeted genomic regions, requiring sequence finishing of large blocks of orthologous sequence (average size 0.5-2 Mb) from various subsets of 75 vertebrates. This experience has provided a unique opportunity to compare the relative effort required to finish shotgun-generated genome sequence assemblies from different species, which we report here. Importantly, we found that the sequence assemblies generated for the same orthologous regions from various vertebrates show substantial variation with respect to misassemblies and, in particular, the frequency and characteristics of sequence gaps. As a consequence, the work required to finish different species' sequences varied greatly. Application of the same standardized methods for finishing provided a novel opportunity to "assay" characteristics of genome sequences among many vertebrate species. It is important to note that many of the problems we have encountered during sequence finishing reflect unique architectural features of a particular vertebrate's genome, which in some cases may have important functional and/or evolutionary implications. Finally, based on our analyses, we have been able to improve our procedures to overcome some of these problems and to increase the overall efficiency of the sequence-finishing process, although significant challenges still remain. Conclusion Our findings have important implications for the eventual finishing of the draft whole-genome sequences that have now been generated for a large number of vertebrates.

Published
2010
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10. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies

Author

Doria-Rose, Nicole A., Schramm, Chaim A., Gorman, Jason, Moore, Penny L., Bhiman, Jinal N., Dekosky, Brandon J., Ernandes, Michael J., Georgiev, Ivelin S., Kim, Helen J., Pancera, Marie, Staupe, Ryan P., Altae-Tran, Han R., Bailer, Robert T., Crooks, Ema T., Cupo, Albert, Druz, Aliaksandr, Garrett, Nigel J., Hoi, Kam H., Kong, Rui, Louder, Mark K., Longo, Nancy S., McKee, Krisha, Nonyane, Molati, O'Dell, Sijy, Roark, Ryan S., Rudicell, Rebecca S., Schmidt, Stephen D., Sheward, Daniel J., Soto, Cinque, Wibmer, Constantinos Kurt, Yang, Yongping, Zhang, Zhenhai, Mullikin, James C., Binley, James M., Sanders, Rogier W., Wilson, Ian A., Moore, John P., Ward, Andrew B., Georgiou, George, Williamson, Carolyn, Abdool Karim, Salim S., Morris, Lynn, Kwong, Peter D., Shapiro, Lawrence, Mascola, John R., Becker, Jesse, Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Johnson, Taccara, Legaspi, Richelle, Lovett, Sean, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Mullikin, James, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, Young, Alice, AII - Amsterdam institute for Infection and Immunity, and Medical Microbiology and Infection Prevention

Subjects
Models, Molecular, Molecular Sequence Data, Population, Antibody Affinity, Somatic hypermutation, HIV Infections, Complementarity determining region, HIV Antibodies, Article, Epitope, Virus, HIV Envelope Protein gp160, Evolution, Molecular, Affinity maturation, Neutralization Tests, Humans, Cell Lineage, Amino Acid Sequence, education, AIDS Vaccines, B-Lymphocytes, education.field_of_study, Binding Sites, Multidisciplinary, biology, Antibodies, Neutralizing, Complementarity Determining Regions, Virology, Protein Structure, Tertiary, Epitope mapping, CD4 Antigens, Immunology, HIV-1, biology.protein, Epitopes, B-Lymphocyte, Somatic Hypermutation, Immunoglobulin, Antibody, Epitope Mapping
Abstract

Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01–12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30–38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development. A longitudinal study of an individual patient developing neutralizing antibodies against HIV-1 (targeting the V1V2 region of gp120) reveals how such neutralizing antibodies develop and evolve over time, providing important insights relevant to vaccine development. A better understanding of how HIV-1-neutralizing antibodies are generated could be a useful contribution to the design of improved AIDS vaccines. John Mascola and colleagues have now elucidated the immunological pathway of an important category of HIV-1-neutralizing antibody — those that target the variable V1V2 region of the viral envelope. These antibodies are more frequently elicited than CD4-binding site antibodies in the early stages of HIV infection and feature modest affinity maturation, a process that favours mutations in antibody variable domains that enhance antigen binding.

Published
2014
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11. A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope

Author

Zhou, Tongqing, primary, Zheng, Anqi, additional, Baxa, Ulrich, additional, Chuang, Gwo-Yu, additional, Georgiev, Ivelin S., additional, Kong, Rui, additional, O’Dell, Sijy, additional, Shahzad-ul-Hussan, Syed, additional, Shen, Chen-Hsiang, additional, Tsybovsky, Yaroslav, additional, Bailer, Robert T., additional, Gift, Syna K., additional, Louder, Mark K., additional, McKee, Krisha, additional, Rawi, Reda, additional, Stevenson, Catherine H., additional, Stewart-Jones, Guillaume B.E., additional, Taft, Justin D., additional, Waltari, Eric, additional, Yang, Yongping, additional, Zhang, Baoshan, additional, Shivatare, Sachin S., additional, Shivatare, Vidya S., additional, Lee, Chang-Chun D., additional, Wu, Chung-Yi, additional, Mullikin, James C., additional, Bewley, Carole A., additional, Burton, Dennis R., additional, Polonis, Victoria R., additional, Shapiro, Lawrence, additional, Wong, Chi-Huey, additional, Mascola, John R., additional, Kwong, Peter D., additional, Wu, Xueling, additional, Benjamin, Betty, additional, Blakesley, Robert, additional, Bouffard, Gerry, additional, Brooks, Shelise, additional, Coleman, Holly, additional, Dekhtyar, Mila, additional, Gregory, Michael, additional, Guan, Xiaobin, additional, Gupta, Jyoti, additional, Han, Joel, additional, Hargrove, April, additional, Ho, Shiling, additional, Legaspi, Richelle, additional, Maduro, Quino, additional, Masiello, Cathy, additional, Maskeri, Baishali, additional, McDowell, Jenny, additional, Montemayor, Casandra, additional, Mullikin, James, additional, Park, Morgan, additional, Riebow, Nancy, additional, Schandler, Karen, additional, Schmidt, Brian, additional, Sison, Christina, additional, Stantripop, Mal, additional, Thomas, James, additional, Thomas, Pam, additional, Vemulapalli, Meg, additional, and Young, Alice, additional

Published
2018
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12. The ClinSeq Project: Piloting large-scale genome sequencing for research in genomic medicine

Author

Biesecker, Leslie G., Mullikin, James C., Facio, Flavia M., Turner, Clesson, Cherukuri, Praveen F., Blakesley, Robert W., Bouffard, Gerard G., Chines, Peter S., Cruz, Pedro, Hansen, Nancy F., Teer, Jamie K., Maskeri, Baishali, Young, Alice C., Manolio, Teri A., Wilson, Alexander F., Finkel, Toren, Hwang, Paul, Arai, Andrew, Remaley, Alan T., Sachdev, Vandana, Shamburek, Robert, Cannon, Richard O., and Green, Eric D.

Subjects
Nucleotide sequence -- Analysis, Human genome -- Research, Medical genetics -- Research, Health
Published
2009

13. An intermediate grade of finished genomic sequence suitable for comparative analyses

Author

Blakesley, Robert W., Vogt, Jennifer L., Shi-Ling Ho, Maskeri, Baishali, Hansen, Nancy F., Walker, Michelle A., Karlins, Eric M., Young, Alice C., Mullikin, James C., Masiello, Catherine A., Maduro, Quino L., Benjamin, Beatrice, Thomas, Pamela J., McDowell, Jennifer C., Green, Eric D., Guan, Xiaobin, Stantrippo, Sirintorn, Brooks, Shelise Y., Bouffard, Gerard G., Tsurgeon, Cyrus, and Gupta, Jyoti

Subjects
Nucleotide sequence -- Research, Genetic research, Health
Abstract

The generation and quality of an intermediate grade of finished genomic sequence, which is tailored for use in multispecies sequence comparisons is described. The results demonstrate that comparative-grade sequence finishing represents a practical and affordable option for sequence refinement en route to comparative analyses.

Published
2004

14. Longitudinal shift in diabetic wound microbiota correlates with prolonged skin defense response

Author

Grice, Elizabeth A., Snitkin, Evan S., Yockey, Laura J., Bermudez, Dustin M., Liechty, Kenneth W., Segre, Julia A., Mullikin, Jim, Blakesley, Robert, Young, Alice, Chu, Grace, Ramsahoye, Colleen, Lovett, Sean, Han, Joel, Legaspi, Richelle, Fuksenko, Tatyana, Reddix-Dugue, Natalie, Sison, Christina, Gregory, Michael, Montemayor, Casandra, Gestole, Marie, Hargrove, April, Johnson, Taccara, Myrick, Jerlil, Riebow, Nancy, Schmidt, Brian, Novotny, Betsy, Gupti, Jyoti, Benjamin, Betty, Brooks, Shelise, Coleman, Holly, Ho, Shi-ling, Schandler, Karen, Smith, Lauren, Stantripop, Mal, Maduro, Quino, Bouffard, Gerry, Dekhtyar, Mila, Guan, Xiaobin, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Park, Morgan, and Jacques Thomas, Pamela

Subjects
Time Factors, Staphylococcus, Molecular Sequence Data, Population Dynamics, Biology, Microbiology, Mice, Immune system, Diabetes mellitus, RNA, Ribosomal, 16S, Gene expression, medicine, Animals, Cluster Analysis, Microbiome, Gene, Skin, Mice, Knockout, Wound Healing, Multidisciplinary, Innate immune system, Bacteria, Gene Expression Profiling, Bacterial Infections, Biodiversity, Sequence Analysis, DNA, Biological Sciences, medicine.disease, Gene expression profiling, Diabetes Mellitus, Type 2, Immunology, Host-Pathogen Interactions, Metagenome, Receptors, Leptin, Female, Wound healing
Abstract

Diabetics frequently suffer from chronic, nonhealing wounds. Although bacterial colonization and/or infection are generally acknowledged to negatively impact wound healing, the precise relationship between the microbial community and impaired wound healing remains unclear. Because the host cutaneous defense response is proposed to play a key role in modulating microbial colonization, we longitudinally examined the diabetic wound microbiome in tandem with host tissue gene expression. By sequencing 16S ribosomal RNA genes, we show that a longitudinal selective shift in wound microbiota coincides with impaired healing in diabetic mice ( Lepr db/db ; db/db). We demonstrate a parallel shift in longitudinal gene expression that occurs in a cluster of genes related to the immune response. Further, we establish a correlation between relative abundance of Staphylococcus spp. and the expression of cutaneous defense response genes. Our data demonstrate that integrating two types of global datasets lends a better understanding to the dynamics governing host–microbe interactions.

Published
2010

15. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection

Author

Wu, Xueling, primary, Zhang, Zhenhai, additional, Schramm, Chaim A., additional, Joyce, M. Gordon, additional, Do Kwon, Young, additional, Zhou, Tongqing, additional, Sheng, Zizhang, additional, Zhang, Baoshan, additional, O’Dell, Sijy, additional, McKee, Krisha, additional, Georgiev, Ivelin S., additional, Chuang, Gwo-Yu, additional, Longo, Nancy S., additional, Lynch, Rebecca M., additional, Saunders, Kevin O., additional, Soto, Cinque, additional, Srivatsan, Sanjay, additional, Yang, Yongping, additional, Bailer, Robert T., additional, Louder, Mark K., additional, Mullikin, James C., additional, Connors, Mark, additional, Kwong, Peter D., additional, Mascola, John R., additional, Shapiro, Lawrence, additional, Benjamin, Betty, additional, Blakesley, Robert, additional, Bouffard, Gerry, additional, Brooks, Shelise, additional, Coleman, Holly, additional, Dekhtyar, Mila, additional, Gregory, Michael, additional, Guan, Xiaobin, additional, Gupta, Jyoti, additional, Han, Joel, additional, Hargrove, April, additional, Ho, Shi-ling, additional, Legaspi, Richelle, additional, Maduro, Quino, additional, Masiello, Cathy, additional, Maskeri, Baishali, additional, McDowell, Jenny, additional, Montemayor, Casandra, additional, Park, Morgan, additional, Riebow, Nancy, additional, Schandler, Karen, additional, Schmidt, Brian, additional, Sison, Christina, additional, Stantripop, Mal, additional, Thomas, James, additional, Thomas, Pam, additional, Vemulapalli, Meg, additional, and Young, Alice, additional

Published
2015
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16. Effort required to finish shotgun-generated genome sequences differs significantly among vertebrates

Author

Blakesley, Robert W, Hansen, Nancy F, Gupta, Jyoti, McDowell, Jennifer C, Maskeri, Baishali, Barnabas, Beatrice B, Brooks, Shelise Y, Coleman, Holly, Haghighi, Payam, Ho, Shi-Ling, Schandler, Karen, Stantripop, Sirintorn, Vogt, Jennifer L, Thomas, Pamela J, Comparative Sequencing Program, NISC, Bouffard, Gerard G, and Green, Eric D

Subjects
Whole genome sequencing, Genetics, Comparative genomics, Chromosomes, Artificial, Bacterial, Genome, lcsh:QH426-470, lcsh:Biotechnology, Chromosome Mapping, Genomics, Computational biology, Genome project, Sequence Analysis, DNA, Biology, DNA sequencing, lcsh:Genetics, lcsh:TP248.13-248.65, Vertebrates, Animals, DNA microarray, Sequence (medicine), Biotechnology, Research Article
Abstract

Background The approaches for shotgun-based sequencing of vertebrate genomes are now well-established, and have resulted in the generation of numerous draft whole-genome sequence assemblies. In contrast, the process of refining those assemblies to improve contiguity and increase accuracy (known as 'sequence finishing') remains tedious, labor-intensive, and expensive. As a result, the vast majority of vertebrate genome sequences generated to date remain at a draft stage. Results To date, our genome sequencing efforts have focused on comparative studies of targeted genomic regions, requiring sequence finishing of large blocks of orthologous sequence (average size 0.5-2 Mb) from various subsets of 75 vertebrates. This experience has provided a unique opportunity to compare the relative effort required to finish shotgun-generated genome sequence assemblies from different species, which we report here. Importantly, we found that the sequence assemblies generated for the same orthologous regions from various vertebrates show substantial variation with respect to misassemblies and, in particular, the frequency and characteristics of sequence gaps. As a consequence, the work required to finish different species' sequences varied greatly. Application of the same standardized methods for finishing provided a novel opportunity to "assay" characteristics of genome sequences among many vertebrate species. It is important to note that many of the problems we have encountered during sequence finishing reflect unique architectural features of a particular vertebrate's genome, which in some cases may have important functional and/or evolutionary implications. Finally, based on our analyses, we have been able to improve our procedures to overcome some of these problems and to increase the overall efficiency of the sequence-finishing process, although significant challenges still remain. Conclusion Our findings have important implications for the eventual finishing of the draft whole-genome sequences that have now been generated for a large number of vertebrates.

Published
2010

17. Somatic Mutational Landscape of AML with Inv(16) and t(8;21) Identifies Two Distinct Patterns in Relapse Tumors

Author

Sood, Raman B., primary, Hansen, Nancy F, additional, Donovan, Frank X, additional, Carrington, Blake, additional, Maskeri, Baishali, additional, Young, Alice, additional, Bucci, Donna, additional, Chandrasekharaappa, Settara, additional, Mullikin, James C, additional, Bloomfield, Clara D., additional, Marcucci, Guido, additional, and Liu, Paul, additional

Published
2014
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18. Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans

Author

Bentley, Amy R., primary, Chen, Guanjie, additional, Shriner, Daniel, additional, Doumatey, Ayo P., additional, Zhou, Jie, additional, Huang, Hanxia, additional, Mullikin, James C., additional, Blakesley, Robert W., additional, Hansen, Nancy F., additional, Bouffard, Gerard G., additional, Cherukuri, Praveen F., additional, Maskeri, Baishali, additional, Young, Alice C., additional, Adeyemo, Adebowale, additional, and Rotimi, Charles N., additional

Published
2014
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19. Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

Author

Margulies, Elliott H, Cooper, Gregory M, Asimenos, George, Thomas, Daryl J, Dewey, Colin N, Siepel, Adam, Birney, Ewan, Keefe, Damian, Schwartz, Ariel S, Hou, Minmei, Taylor, James, Nikolaev, Sergey, Montoya-Burgos, Juan I, Löytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Brown, James B, Bickel, Peter, Holmes, Ian, Mullikin, James C, Ureta-Vidal, Abel, Paten, Benedict, Stone, Eric A, Rosenbloom, Kate R, Kent, W James, Bouffard, Gerard G, Guan, Xiaobin, Hansen, Nancy F, Idol, Jacquelyn R, Maduro, Valerie V B, Maskeri, Baishali, McDowell, Jennifer C, Park, Morgan, Thomas, Pamela J, Young, Alice C, Blakesley, Robert W, Muzny, Donna M, Sodergren, Erica, Wheeler, David A, Worley, Kim C, Jiang, Huaiyang, Weinstock, George M, Gibbs, Richard A, Graves, Tina, Fulton, Robert, Mardis, Elaine R, Wilson, Richard K, Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B, Chang, Jean L, Lindblad-Toh, Kerstin, Lander, Eric S, Hinrichs, Angie, Trumbower, Heather, Clawson, Hiram, Zweig, Ann, Kuhn, Robert M, Barber, Galt, Harte, Rachel, Karolchik, Donna, Field, Matthew A, Moore, Richard A, Matthewson, Carrie A, Schein, Jacqueline E, Marra, Marco A, Antonarakis, Stylianos E, Batzoglou, Serafim, Goldman, Nick, Hardison, Ross, Haussler, David, Miller, Webb, Pachter, Lior, Green, Eric D, Sidow, Arend, Margulies, Elliott H, Cooper, Gregory M, Asimenos, George, Thomas, Daryl J, Dewey, Colin N, Siepel, Adam, Birney, Ewan, Keefe, Damian, Schwartz, Ariel S, Hou, Minmei, Taylor, James, Nikolaev, Sergey, Montoya-Burgos, Juan I, Löytynoja, Ari, Whelan, Simon, Pardi, Fabio, Massingham, Tim, Brown, James B, Bickel, Peter, Holmes, Ian, Mullikin, James C, Ureta-Vidal, Abel, Paten, Benedict, Stone, Eric A, Rosenbloom, Kate R, Kent, W James, Bouffard, Gerard G, Guan, Xiaobin, Hansen, Nancy F, Idol, Jacquelyn R, Maduro, Valerie V B, Maskeri, Baishali, McDowell, Jennifer C, Park, Morgan, Thomas, Pamela J, Young, Alice C, Blakesley, Robert W, Muzny, Donna M, Sodergren, Erica, Wheeler, David A, Worley, Kim C, Jiang, Huaiyang, Weinstock, George M, Gibbs, Richard A, Graves, Tina, Fulton, Robert, Mardis, Elaine R, Wilson, Richard K, Clamp, Michele, Cuff, James, Gnerre, Sante, Jaffe, David B, Chang, Jean L, Lindblad-Toh, Kerstin, Lander, Eric S, Hinrichs, Angie, Trumbower, Heather, Clawson, Hiram, Zweig, Ann, Kuhn, Robert M, Barber, Galt, Harte, Rachel, Karolchik, Donna, Field, Matthew A, Moore, Richard A, Matthewson, Carrie A, Schein, Jacqueline E, Marra, Marco A, Antonarakis, Stylianos E, Batzoglou, Serafim, Goldman, Nick, Hardison, Ross, Haussler, David, Miller, Webb, Pachter, Lior, Green, Eric D, and Sidow, Arend

Abstract

A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.

Published
2007
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20. Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

Author

Margulies, Elliott H., primary, Cooper, Gregory M., additional, Asimenos, George, additional, Thomas, Daryl J., additional, Dewey, Colin N., additional, Siepel, Adam, additional, Birney, Ewan, additional, Keefe, Damian, additional, Schwartz, Ariel S., additional, Hou, Minmei, additional, Taylor, James, additional, Nikolaev, Sergey, additional, Montoya-Burgos, Juan I., additional, Löytynoja, Ari, additional, Whelan, Simon, additional, Pardi, Fabio, additional, Massingham, Tim, additional, Brown, James B., additional, Bickel, Peter, additional, Holmes, Ian, additional, Mullikin, James C., additional, Ureta-Vidal, Abel, additional, Paten, Benedict, additional, Stone, Eric A., additional, Rosenbloom, Kate R., additional, Kent, W. James, additional, Bouffard, Gerard G., additional, Guan, Xiaobin, additional, Hansen, Nancy F., additional, Idol, Jacquelyn R., additional, Maduro, Valerie V.B., additional, Maskeri, Baishali, additional, McDowell, Jennifer C., additional, Park, Morgan, additional, Thomas, Pamela J., additional, Young, Alice C., additional, Blakesley, Robert W., additional, Muzny, Donna M., additional, Sodergren, Erica, additional, Wheeler, David A., additional, Worley, Kim C., additional, Jiang, Huaiyang, additional, Weinstock, George M., additional, Gibbs, Richard A., additional, Graves, Tina, additional, Fulton, Robert, additional, Mardis, Elaine R., additional, Wilson, Richard K., additional, Clamp, Michele, additional, Cuff, James, additional, Gnerre, Sante, additional, Jaffe, David B., additional, Chang, Jean L., additional, Lindblad-Toh, Kerstin, additional, Lander, Eric S., additional, Hinrichs, Angie, additional, Trumbower, Heather, additional, Clawson, Hiram, additional, Zweig, Ann, additional, Kuhn, Robert M., additional, Barber, Galt, additional, Harte, Rachel, additional, Karolchik, Donna, additional, Field, Matthew A., additional, Moore, Richard A., additional, Matthewson, Carrie A., additional, Schein, Jacqueline E., additional, Marra, Marco A., additional, Antonarakis, Stylianos E., additional, Batzoglou, Serafim, additional, Goldman, Nick, additional, Hardison, Ross, additional, Haussler, David, additional, Miller, Webb, additional, Pachter, Lior, additional, Green, Eric D., additional, and Sidow, Arend, additional

Published
2007
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21. Somatic mutational landscape of AML with inv(16) or t(8;21) identifies patterns of clonal evolution in relapse leukemia

Author

Sood, Raman, Hansen, Nancy F., Donovan, Frank X., Carrington, Blake, Bucci, Donna, Maskeri, Baishali, Young, Alice, Trivedi, Niraj S., Kohlschmidt, Jessica, Stone, Richard M., Caligiuri, Michael A., Chandrasekharappa, Settara C., Marcucci, Guido, Mullikin, James C., Bloomfield, Clara D., and Liu, Paul

Subjects
t(8, 21), inv(16), relapse, AML
Published
2015
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22. Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma

Author

Gartner, Jared J., Parker, Stephen C. J., Prickett, Todd D., Dutton-Regester, Kenneth Adam, Stitzel, Michael L., Lin, Jimmy C., Davis, Sean, Simhadri, Vijaya L., Jha, Sujata, Katagiri, Nobuko, Gotea, Valer, Teer, Jamie K., Wei, Xiaomu, Morken, Mario A., Bhanot, Umesh K., Chen, Guo, Elnitski, Laura L., Davies, Michael A., Gershenwald, Jeffrey E., Carter, Hannah, Karchin, Rachel, Robinson, William, Robinson, Steven, Rosenberg, Steven A., Collins, Francis S., Parmigiani, Giovanni, Komar, Anton A., Kimchi-Sarfaty, Chava, Hayward, Nicholas K., Margulies, Elliott H., Samuels, Yardena, Becker, Jesse, Benjamin, Betty, Blakesley, Robert, Bouffard, Gerry, Brooks, Shelise, Coleman, Holly, Dekhtyar, Mila, Gregory, Michael, Guan, Xiaobin, Gupta, Jyoti, Han, Joel, Hargrove, April, Ho, Shi-ling, Johnson, Taccara, Legaspi, Richelle, Lovett, Sean, Maduro, Quino, Masiello, Cathy, Maskeri, Baishali, McDowell, Jenny, Montemayor, Casandra, Mullikin, James, Park, Morgan, Riebow, Nancy, Schandler, Karen, Schmidt, Brian, Sison, Christina, Stantripop, Mal, Thomas, James, Thomas, Pam, Vemulapalli, Meg, and Young, Alice

Abstract

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683–691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671–5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies.

Published
2013
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