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2. 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
Genetic research, Human genome -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

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., 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]; [...]

Published
2012
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3. A cis-regulatory map of the Drosophila genome

Author

Nègre, Nicolas, Brown, Christopher D., Ma, Lijia, Bristow, Christopher Aaron, Miller, Steven W., Wagner, Ulrich, Kheradpour, Pouya, Eaton, Matthew L., Loriaux, Paul, Sealfon, Rachel, Li, Zirong, Ishii, Haruhiko, Spokony, Rebecca F., Chen, Jia, Hwang, Lindsay, Cheng, Chao, Auburn, Richard P., Davis, Melissa B., Domanus, Marc, Shah, Parantu K., Morrison, Carolyn A., Zieba, Jennifer, Suchy, Sarah, Senderowicz, Lionel, Victorsen, Alec, Bild, Nicholas A., Grundstad, Jason A., Hanley, David, MacAlpine, David M., Mannervik, Mattias, Venken, Koen, Bellen, Hugo, White, Robert, Gerstein, Mark, Russell, Steven, Grossman, Robert L., Ren, Bing, Posakony, James W., Kellis, Manolis, and White, Kevin P.

Published
2011
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6. Small Molecule and Pooled CRISPR Screens Investigating IL17 Signaling Identify BRD2 as a Novel Contributor to Keratinocyte Inflammatory Responses

Author

Slivka, Peter F., primary, Hsieh, Chen-Lin, additional, Lipovsky, Alex, additional, Pratt, Steven D., additional, Locklear, John, additional, Namovic, Marian T., additional, McDonald, Heath A., additional, Wetter, Joseph, additional, Edelmayer, Rebecca, additional, Hu, Min, additional, Murphy, Erin, additional, Domanus, Marc, additional, Lu, Charles, additional, Duggan, Ryan, additional, King, Jacob, additional, Scott, Victoria E., additional, Donnelly-Roberts, Diana, additional, Slavin, Anthony, additional, Gopalakrishnan, Sujatha, additional, Chung, Namjin, additional, and Goedken, Eric R., additional

Published
2019
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7. BMP signaling components in embryonic transcriptomes of the hover fly Episyrphus balteatus (Syrphidae)

Author

Domanus Marc H, Meyer Folker, Antonopoulos Dionysios A, Lemke Steffen, and Schmidt-Ott Urs

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

Abstract Background In animals, signaling of Bone Morphogenetic Proteins (BMPs) is essential for dorsoventral (DV) patterning of the embryo, but how BMP signaling evolved with changes in embryonic DV differentiation is largely unclear. Based on the extensive knowledge of BMP signaling in Drosophila melanogaster, the morphological diversity of extraembryonic tissues in different fly species provides a comparative system to address this question. The closest relatives of D. melanogaster with clearly distinct DV differentiation are hover flies (Diptera: Syrphidae). The syrphid Episyrphus balteatus is a commercial bio-agent against aphids and has been established as a model organism for developmental studies and chemical ecology. The dorsal blastoderm of E. balteatus gives rise to two extraembryonic tissues (serosa and amnion), whereas in D. melanogaster, the dorsal blastoderm differentiates into a single extraembryonic epithelium (amnioserosa). Recent studies indicate that several BMP signaling components of D. melanogaster, including the BMP ligand Screw (Scw) and other extracellular regulators, evolved in the dipteran lineage through gene duplication and functional divergence. These findings raise the question of whether the complement of BMP signaling components changed with the origin of the amnioserosa. Results To search for BMP signaling components in E. balteatus, we generated and analyzed transcriptomes of freshly laid eggs (0-30 minutes) and late blastoderm to early germband extension stages (3-6 hours) using Roche/454 sequencing. We identified putative E. balteatus orthologues of 43% of all annotated D. melanogaster genes, including the genes of all BMP ligands and other BMP signaling components. Conclusion The diversification of several BMP signaling components in the dipteran linage of D. melanogaster preceded the origin of the amnioserosa. [Transcriptome sequence data from this study have been deposited at the NCBI Sequence Read Archive (SRP005289); individually assembled sequences have been deposited at GenBank (JN006969-JN006986).]

Published
2011
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8. Identification of functional elements and regulatory circuits by Drosophila modENCODE

Author

Roy, Sushmita, Ernst, Jason, Kharchenko, Peter V., Kheradpour, Pouya, Negre, Nicolas, Eaton, Matthew L., Landolin, Jane M., Bristow, Christopher A., Ma, Lijia, Lin, Michael F., Washietl, Stefan, Arshinoff, Bradley I., Ay, Ferhat, Meyer, Patrick E., Robine, Nicolas, Washington, Nicole L., Di Stefano, Luisa, Berezikov, Eugene, Brown, Christopher D., Candeias, Rogerio, Carlson, Joseph W., Carr, Adrian, Jungreis, Irwin, Marbach, Daniel, Sealfon, Rachel, Tolstorukov, Michael Y., Will, Sebastian, Alekseyenko, Artyom A., Artieri, Carlo, Booth, Benjamin W., Brooks, Angela N., Dai, Qi, Davis, Carrie A., Duff, Michael O., Feng, Xin, Gorchakov, Andrey A., Gu, Tingting, Henikoff, Jorja G., Kapranov, Philipp, Li, Renhua, MacAlpine, Heather K., Malone, John, Minoda, Aki, Nordman, Jared, Okamura, Katsutomo, Perry, Marc, Powell, Sara K., Riddle, Nicole C., Sakai, Akiko, Samsonova, Anastasia A., Sandler, Jeremy E., Schwartz, Yuri B., Sher, Noa, Spokony, Rebecca, Sturgill, David, van Baren, Marijke, Wan, Kenneth H., Yang, Li, Yu, Charles, Feingold, Elise, Good, Peter, Guyer, Mark, Lowdon, Rebecca, Ahmad, Kami, Andrews, Justen, Berger, Bonnie, Brenner, Steven E., Brent, Michael R., Cherbas, Lucy, Elgin, Sarah C.R., Gingeras, Thomas R., Grossman, Robert, Hoskins, Roger A., Kaufman, Thomas C., Kent, William, Kuroda, Mitzi I., Orr-Weaver, Terry, Perrimon, Norbert, Pirrotta, Vincenzo, Posakony, James W., Ren, Bing, Russell, Steven, Cherbas, Peter, Graveley, Brenton R., Lewis, Suzanna, Micklem, Gos, Oliver, Brian, Park, Peter J., Celniker, Susan E., Henikoff, Steven, Karpen, Gary H., Lai, Eric C., MacAlpine, David M., Stein, Lincoln D., White, Kevin P., Kellis, Manolis, Booth, Benjamin, Comstock, Charles L.G., Dobin, Alex, Drenkow, Jorg, Dudoit, Sandrine, Dumais, Jacqueline, Fagegaltier, Delphine, Ghosh, Srinka, Hansen, Kasper D., Jha, Sonali, Langton, Laura, Lin, Wei, Miller, David, Tenney, Aaron E., Wang, Huaien, Willingham, Aarron T., Zaleski, Chris, Zhang, Dayu, Acevedo, David, Bishop, Eric P., Gadel, Sarah E., Jung, Youngsook L., Kennedy, Cameron D., Lee, Ok Kyung, Linder-Basso, Daniela, Marchetti, Sarah E., Shanower, Gregory, Nègre, Nicolas, Grossman, Robert L., Auburn, Richard, Bellen, Hugo J., Chen, Jia, Domanus, Marc H., Hanley, David, Heinz, Elizabeth, Li, Zirong, Meyer, Folker, Miller, Steven W., Morrison, Carolyn A., Scheftner, Douglas A., Senderowicz, Lionel, Shah, Parantu K., Suchy, Sarah, Tian, Feng, Venken, Koen J.T., White, Robert, Wilkening, Jared, Zieba, Jennifer, Nordman, Jared T., Orr-Weaver, Terry L., DeNapoli, Leyna C., Ding, Queying, Eng, Thomas, Kashevsky, Helena, Li, Sharon, Prinz, Joseph A., Hannon, Gregory J., Hirst, Martin, Marra, Marco, Rooks, Michelle, Zhao, Yongjun, Bryson, Terri D., Perry, Marc D., Kent, William J., Lewis, Suzanna E., Barber, Galt, Chateigner, Aurelien, Clawson, Hiram, Contrino, Sergio, Guillier, Francois, Hinrichs, Angie S., Kephart, Ellen T., Lloyd, Paul, Lyne, Rachel, McKay, Sheldon, Moore, Richard A., Mungall, Chris, Rutherford, Kim M., Ruzanov, Peter, Smith, Richard, Stinson, E. O., Zha, Zheng, Artieri, Carlo G., Malone, John H., Jiang, Lichun, Mattiuzzo, Nicolas, Feingold, Elise A., Good, Peter J., Guyer, Mark S., Lowdon, Rebecca F., Stem Cell Aging Leukemia and Lymphoma (SALL), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)

Subjects
Transcription, Genetic, Genome, Insect, Gene regulatory network, Genomics, Genes, Insect, Computational biology, Biology, Genome, Article, Epigenesis, Genetic, Histones, Nucleosome, Animals, Drosophila Proteins, Gene Regulatory Networks, Promoter Regions, Genetic, Gene, Genetics, Multidisciplinary, Binding Sites, REDfly, Computational Biology, Molecular Sequence Annotation, Chromatin, Nucleosomes, Drosophila melanogaster, Gene Expression Regulation, RNA, Small Untranslated, Drosophila Protein, Transcription Factors
Abstract

From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation is still needed to characterize how the genome is used to help to produce a functional organism (see the Perspective by Blaxter ). In this vein, Gerstein et al. (p. 1775 ) summarize for the Caenorhabditis elegans genome, and The modENCODE Consortium (p. 1787 ) summarize for the Drosophila melanogaster genome, full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites, and high-resolution maps of chromatin organization. Both studies identified regions of the nematode and fly genomes that show highly occupied targets (or HOT) regions where DNA was bound by more than 15 of the transcription factors analyzed and the expression of related genes were characterized. Overall, the studies provide insights into the organization, structure, and function of the two genomes and provide basic information needed to guide and correlate both focused and genome-wide studies.

Published
2010

9. A highly reproducible, linear, and automated sample preparation method for DNA microarrays

Author

Dorris, David R., Ramakrishnan, Ramesh, Trakas, Dionisios, Dudzik, Frank, Belval, Richard, Mazumder, Abhijit, Domanus, Marc, Nguyen, Allen, and Zhao, Connie

Subjects
Genetic transcription -- Research, Antisense DNA -- Research, RNA -- Research, DNA microarrays -- Research, Genetic research, Health
Abstract

An optimized target-preparation method that converted the poly (A)+ RNA fraction of the total RNA into complementary DNA was invented to detect changes when differential transcript abundance samples are used. RNA mixing experiments showed a linear and quantitative amplification in probe hybridization signals for >6000 genes across the entire signal range.

Published
2002

10. P092

Author

Jabara, Cassandra, primary, Domanus, Marc, additional, Kim, Dae Hyun, additional, Ho, Shiaolan, additional, Adema, Jeroen, additional, Westerink, Nienke, additional, and Marlowe, Natalia, additional

Published
2014
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13. Nanoparticle-Based Biobarcode Amplification Assay (BCA) for Sensitive and Early Detection of Human Immunodeficiency Type 1 Capsid (p24) Antigen

Author

Tang, Shixing, primary, Zhao, Jiangqin, additional, Storhoff, James J, additional, Norris, Philip J, additional, Little, Richard F, additional, Yarchoan, Robert, additional, Stramer, Susan L, additional, Patno, Tim, additional, Domanus, Marc, additional, Dhar, Arindam, additional, Mirkin, Chad A, additional, and Hewlett, Indira K, additional

Published
2007
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14. Novel UNC‐44 AO13 ankyrin is required for axonal guidance in C. elegans, contains six highly repetitive STEP blocks separated by seven potential transmembrane domains, and is localized to neuronal processes and the periphery of neural cell bodies

Author

Otsuka, Anthony J., primary, Boontrakulpoontawee, Pratumtip, additional, Rebeiz, Natalie, additional, Domanus, Marc, additional, Otsuka, Dawn, additional, Velamparampil, Nena, additional, Chan, Sabrina, additional, Wyngaerde, Marshall Vande, additional, Campagna, Sarah, additional, and Cox, Andrea, additional

Published
2002
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16. Novel UNC-44 AO13 ankyrin is required for axonal guidance in <TOGGLE>C. elegans</TOGGLE>, contains six highly repetitive STEP blocks separated by seven potential transmembrane domains, and is localized to neuronal processes and the periphery of neural cell bodies

Author

Otsuka, Anthony J., Boontrakulpoontawee, Pratumtip, Rebeiz, Natalie, Domanus, Marc, Otsuka, Dawn, Velamparampil, Nena, Chan, Sabrina, Wyngaerde, Marshall Vande, Campagna, Sarah, and Cox, Andrea

Abstract

Conventional ankyrins are cortical cytoskeletal proteins that form an ankyrin-spectrin meshwork underlying the plasma membrane. We report here the unusual structure of a novel ankyrin (AO13 ankyrin, 775,369 Da, 6994 aa, pI = 4.45) that is required for proper axonal guidance in Caenorhabditis elegans. AO13 ankyrin contains the ANK repeat and spectrin-binding domains found in other ankyrins, but differs from all others in that the acidic carboxyl region contains six blocks of serine/threonine/glutamic acid/proline rich (STEP) repeats separated by seven hydrophobic domains. The STEP repeat blocks are composed primarily of sequences related to ETTTTTTVTREHFEPED(E/D)XnVVESEEYSASGSPVPSE (E/K)DVE(H/R)VI, and the hydrophobic domains contain sequences related to PESGEESDGEGFGSKVLGFAKK[AGMVAGGVVAAPVALAAVGA]KAAYDALKKDDDEE, which includes a potential transmembrane domain (in brackets). Recombinant protein fragments of AO13 ankyrin were used to prepare polyclonal antisera against the spectrin-binding domain (AO271 Ab), the conventional ankyrin regulatory domain (AO280 Ab), the AO13 ankyrin STEP domain (AO346 Ab), the AO13 ankyrin STEP + hydrophobic domain (AO289 Ab), and against two carboxyl terminal domain fragments (AO263 Ab and AO327 Ab). Western blot analysis with these Ab probes demonstrated multiple protein isoforms. By immunofluorescence microscopy, the antispectrin-binding and regulatory domain (AO271 and AO280) antibodies recognized many cell types, including neurons, and stained the junctions between cells. The AO13 ankyrin-specific (AO289 and AO346) antibodies showed a neurally restricted pattern, staining nerve processes and the periphery of neural cell bodies. These results are consistent with a role for AO13 ankyrin in neural development. © 2002 Wiley Periodicals, Inc. J Neurobiol 50: 333–349, 2002; DOI 10.1002/neu.10036

Published
2002
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17. P092 : PERFORMANCE EVALUATION OF HIGH RESOLUTION 11 LOCI HLA-TYPING PROTOTYPE ASSAY USING NGS TECHNOLOGY.

Author

Jabara, Cassandra, Domanus, Marc, Kim, Dae Hyun, Ho, Shiaolan, Adema, Jeroen, Westerink, Nienke, and Marlowe, Natalia

Subjects
*PERFORMANCE evaluation, *HLA histocompatibility antigens, *WORKFLOW, *POLYMERASE chain reaction, *GENE amplification, *EXONS (Genetics)
Abstract

Aim The aim of this study was to evaluate the workflow and performance of a NGS-based high resolution HLA typing prototype assay developed by GenDx. Methods 48 UCLA reference panel samples were amplified at 11 loci (HLA-A, B, C, DRB1, DRB3/4/5, DQB1, DQA1, DPB, DPA) using NGS-go® primers with Long-Range (LR) PCR and sequenced on the Illumina MiSeq platform. A full gene (5’ UTR to 3’ UTR) amplification strategy was applied with the exception of DRB1 which amplified from exon 2 to exon 4. Individual amplicons were generated for each sample using 100 ng of gDNA per LR-PCR reaction. Intrapatient amplicons were pooled, enzymatically fragmented, and purified. Purified fragmented dsDNA was brought through library preparation using NEBNext (New England Biolabs) for MiSeq sequencing. Due to the limited number of indices (24) in NEBNext, two 2 × 150 paired-end sequencing runs were completed with each run containing 24 samples. Demultiplexed reads were aligned and typed using GenDx NGSengine® v1.4.0 (IMGT v 3.15.0) and Omixon Target v1.8.0 (IMGT v 3.10.0) software. Results 47/48 UCLA samples successfully amplified; a single sample failed potentially due to gDNA integrity. For HLA-A, B, C, DRB1, DQB1, DQA1, DPB and DPA an average of 5 μ g of dsDNA was produced per amplicon, and 99.7% agreed with the reference SBT allele assignments. In one sample DRB1 04:05/15:02 were mistyped by both software packages. SBT reference typing was not available for DRB3/4/5, however when both software packages called a loci, there was 100% agreement at 4 digit allele typing level. Average sequencing output was 3.65 Gb of sequence (12 million paired sequence reads) per run and a mean of 459,573 (median: 433,292) paired-end reads per sample. Conclusion We have demonstrated that GenDx’s NGS HLA typing assay has high accuracy, throughput, and provided unambiguous high resolution results for 47/48 UCLA reference panel samples. This assay delivered full genomic sequences for all targeted HLA loci except DRB1 exon 1 and had the capacity to analyze 11 loci for 24 samples per MiSeq run. [ABSTRACT FROM AUTHOR]

Published
2014
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18. VHL Synthetic Lethality Signatures Uncovered by Genotype-Specific CRISPR-Cas9 Screens.

Author

Sun N, Petiwala S, Lu C, Hutti JE, Hu M, Hu M, Domanus MH, Mitra D, Addo SN, Miller CP, and Chung N

Subjects
CRISPR-Cas Systems, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell metabolism, Cell Line, Tumor, DNA Damage, Gene Editing, Humans, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, Sequence Analysis, RNA, Von Hippel-Lindau Tumor Suppressor Protein genetics, von Hippel-Lindau Disease genetics, von Hippel-Lindau Disease metabolism, DNA Repair, Selenocysteine biosynthesis, Signal Transduction, Von Hippel-Lindau Tumor Suppressor Protein metabolism
Abstract

Genome-wide CRISPR-Cas9 essentiality screening represents a powerful approach to identify genetic vulnerabilities in cancer cells. Here, we applied this technology and designed a strategy to identify target genes that are synthetic lethal (SL) with von Hippel-Lindau ( VHL ) tumor suppressor gene. Inactivation of VHL has been frequently found in clear cell renal cell carcinoma. Its SL partners serve as potential drug targets for the development of targeted cancer therapies. We performed parallel genome-wide CRISPR screens in two pairs of isogenic clear cell renal cell carcinoma cell lines that differ only in the VHL status. Comparative analyses of screening results not only confirmed a well-known role for mTOR signaling in renal carcinoma, but also identified DNA damage response and selenocysteine biosynthesis pathways as novel SL targets in VHL- inactivated cancer cells. Follow-up studies provided cellular and mechanistic insights into SL interactions of these pathway genes with the VHL gene. Our CRISPR and RNA-seq datasets provide a rich resource for future investigation of the function of the VHL tumor suppressor protein. Our work demonstrates the efficiency of CRISPR-based synthetic lethality screening in human isogenic cell pairs. Similar strategies could be employed to unveil SL partners with other oncogenic drivers.

Published
2019
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19. Nanoparticle-Based biobarcode amplification assay (BCA) for sensitive and early detection of human immunodeficiency type 1 capsid (p24) antigen.

Author

Tang S, Zhao J, Storhoff JJ, Norris PJ, Little RF, Yarchoan R, Stramer SL, Patno T, Domanus M, Dhar A, Mirkin CA, and Hewlett IK

Subjects
HIV Core Protein p24 immunology, HIV Infections immunology, Humans, Sensitivity and Specificity, Time Factors, Viral Load, HIV Antibodies, HIV Core Protein p24 analysis, HIV Infections diagnosis, HIV-1, Immunologic Tests methods, Nanoparticles, Nucleic Acid Amplification Techniques methods
Abstract

Nanotechnology-based techniques are being widely evaluated in medical testing and could provide a new generation of diagnostic assays due to their high degrees of sensitivity, high specificity, multiplexing capabilities, and ability to operate without enzymes. In this article, we have modified a nanoparticle-based biobarcode amplification (BCA) assay for early and sensitive detection of HIV-1 capsid (p24) antigen by using antip24 antibody-coated microplates to capture viral antigen (p24) and streptavidin-coated nanoparticle-based biobarcode DNAs for signal amplification, followed by detection using a chip-based scanometric method. The modified BCA assay exhibited a linear dose-dependent pattern within the detection range of 0.1 to 500 pg/ml and was approximately 150-fold more sensitive than conventional enzyme-linked immunosorbent assay (ELISA). No false positive results were observed in 30 HIV-1-negative samples, while all 45 HIV-1 RNA positive samples were found HIV-1 p24 antigen positive by the BCA assay. In addition, the BCA assay detected HIV-1 infection 3 days earlier than ELISA in seroconversion samples. Preliminary evaluation based on testing a small number of samples indicates that the HIV-1 p24 antigen BCA may provide a new tool for sensitive and early detection of HIV-1 p24 antigen in settings where HIV-1 RNA testing is currently not routinely performed.

Published
2007
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20. Sensitive assay for identification of methicillin-resistant Staphylococcus aureus, based on direct detection of genomic DNA by use of gold nanoparticle probes.

Author

Ramakrishnan R, Buckingham W, Domanus M, Gieser L, Klein K, Kunkel G, Prokhorova A, and Riccelli PV

Subjects
Bacteriological Techniques methods, Nanotechnology, Oligonucleotide Array Sequence Analysis, Oligonucleotides chemistry, Particle Size, Sensitivity and Specificity, Staphylococcus aureus drug effects, Staphylococcus aureus isolation & purification, Staphylococcus epidermidis drug effects, Staphylococcus epidermidis genetics, DNA, Bacterial analysis, Gold chemistry, Methicillin Resistance, Staphylococcus aureus genetics
Published
2004
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