42 results on '"Mamanova, Lira"'
Search Results
2. Human SARS-CoV-2 challenge uncovers local and systemic response dynamics
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Lindeboom, Rik G. H., Worlock, Kaylee B., Dratva, Lisa M., Yoshida, Masahiro, Scobie, David, Wagstaffe, Helen R., Richardson, Laura, Wilbrey-Clark, Anna, Barnes, Josephine L., Kretschmer, Lorenz, Polanski, Krzysztof, Allen-Hyttinen, Jessica, Mehta, Puja, Sumanaweera, Dinithi, Boccacino, Jacqueline M., Sungnak, Waradon, Elmentaite, Rasa, Huang, Ni, Mamanova, Lira, Kapuge, Rakesh, Bolt, Liam, Prigmore, Elena, Killingley, Ben, Kalinova, Mariya, Mayer, Maria, Boyers, Alison, Mann, Alex, Swadling, Leo, Woodall, Maximillian N. J., Ellis, Samuel, Smith, Claire M., Teixeira, Vitor H., Janes, Sam M., Chambers, Rachel C., Haniffa, Muzlifah, Catchpole, Andrew, Heyderman, Robert, Noursadeghi, Mahdad, Chain, Benny, Mayer, Andreas, Meyer, Kerstin B., Chiu, Christopher, Nikolić, Marko Z., and Teichmann, Sarah A.
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- 2024
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3. HOX gene expression in the developing human spine
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Lawrence, John E. G., Roberts, Kenny, Tuck, Elizabeth, Li, Tong, Mamanova, Lira, Balogh, Petra, Usher, Inga, Piapi, Alice, Mazin, Pavel, Anderson, Nathaniel D., Bolt, Liam, Richardson, Laura, Prigmore, Elena, He, Xiaoling, Barker, Roger A., Flanagan, Adrienne, Young, Matthew D., Teichmann, Sarah A., Bayraktar, Omer, and Behjati, Sam
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- 2024
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4. Systematic benchmarking of single-cell ATAC-sequencing protocols
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De Rop, Florian V., Hulselmans, Gert, Flerin, Chris, Soler-Vila, Paula, Rafels, Albert, Christiaens, Valerie, González-Blas, Carmen Bravo, Marchese, Domenica, Caratù, Ginevra, Poovathingal, Suresh, Rozenblatt-Rosen, Orit, Slyper, Michael, Luo, Wendy, Muus, Christoph, Duarte, Fabiana, Shrestha, Rojesh, Bagdatli, S. Tansu, Corces, M. Ryan, Mamanova, Lira, Knights, Andrew, Meyer, Kerstin B., Mulqueen, Ryan, Taherinasab, Akram, Maschmeyer, Patrick, Pezoldt, Jörn, Lambert, Camille Lucie Germaine, Iglesias, Marta, Najle, Sebastián R., Dossani, Zain Y., Martelotto, Luciano G., Burkett, Zach, Lebofsky, Ronald, Martin-Subero, José Ignacio, Pillai, Satish, Sebé-Pedrós, Arnau, Deplancke, Bart, Teichmann, Sarah A., Ludwig, Leif S., Braun, Theodore P., Adey, Andrew C., Greenleaf, William J., Buenrostro, Jason D., Regev, Aviv, Aerts, Stein, and Heyn, Holger
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- 2024
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5. Age-specific nasal epithelial responses to SARS-CoV-2 infection
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Woodall, Maximillian N. J., Cujba, Ana-Maria, Worlock, Kaylee B., Case, Katie-Marie, Masonou, Tereza, Yoshida, Masahiro, Polanski, Krzysztof, Huang, Ni, Lindeboom, Rik G. H., Mamanova, Lira, Bolt, Liam, Richardson, Laura, Cakir, Batuhan, Ellis, Samuel, Palor, Machaela, Burgoyne, Thomas, Pinto, Andreia, Moulding, Dale, McHugh, Timothy D., Saleh, Aarash, Kilich, Eliz, Mehta, Puja, O’Callaghan, Chris, Zhou, Jie, Barclay, Wendy, De Coppi, Paolo, Butler, Colin R., Cortina-Borja, Mario, Vinette, Heloise, Roy, Sunando, Breuer, Judith, Chambers, Rachel C., Heywood, Wendy E., Mills, Kevin, Hynds, Robert E., Teichmann, Sarah A., Meyer, Kerstin B., Nikolić, Marko Z., and Smith, Claire M.
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- 2024
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6. Author Correction: Age-specific nasal epithelial responses to SARS-CoV-2 infection
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Woodall, Maximillian N. J., Cujba, Ana-Maria, Worlock, Kaylee B., Case, Katie-Marie, Masonou, Tereza, Yoshida, Masahiro, Polanski, Krzysztof, Huang, Ni, Lindeboom, Rik G. H., Mamanova, Lira, Bolt, Liam, Richardson, Laura, Cakir, Batuhan, Ellis, Samuel, Palor, Machaela, Burgoyne, Thomas, Pinto, Andreia, Moulding, Dale, McHugh, Timothy D., Saleh, Aarash, Kilich, Eliz, Mehta, Puja, O’Callaghan, Chris, Zhou, Jie, Barclay, Wendy, De Coppi, Paolo, Butler, Colin R., Cortina-Borja, Mario, Vinette, Heloise, Roy, Sunando, Breuer, Judith, Chambers, Rachel C., Heywood, Wendy E., Mills, Kevin, Hynds, Robert E., Teichmann, Sarah A., Meyer, Kerstin B., Nikolić, Marko Z., and Smith, Claire M.
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- 2024
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7. Author Correction: Human SARS-CoV-2 challenge uncovers local and systemic response dynamics
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Lindeboom, Rik G. H., Worlock, Kaylee B., Dratva, Lisa M., Yoshida, Masahiro, Scobie, David, Wagstaffe, Helen R., Richardson, Laura, Wilbrey-Clark, Anna, Barnes, Josephine L., Kretschmer, Lorenz, Polanski, Krzysztof, Allen-Hyttinen, Jessica, Mehta, Puja, Sumanaweera, Dinithi, Boccacino, Jacqueline M., Sungnak, Waradon, Elmentaite, Rasa, Huang, Ni, Mamanova, Lira, Kapuge, Rakesh, Bolt, Liam, Prigmore, Elena, Killingley, Ben, Kalinova, Mariya, Mayer, Maria, Boyers, Alison, Mann, Alex, Swadling, Leo, Woodall, Maximillian N. J., Ellis, Samuel, Smith, Claire M., Teixeira, Vitor H., Janes, Sam M., Chambers, Rachel C., Haniffa, Muzlifah, Catchpole, Andrew, Heyderman, Robert, Noursadeghi, Mahdad, Chain, Benny, Mayer, Andreas, Meyer, Kerstin B., Chiu, Christopher, Nikolić, Marko Z., and Teichmann, Sarah A.
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- 2024
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8. Spatially resolved multiomics of human cardiac niches
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Kanemaru, Kazumasa, Cranley, James, Muraro, Daniele, Miranda, Antonio M. A., Ho, Siew Yen, Wilbrey-Clark, Anna, Patrick Pett, Jan, Polanski, Krzysztof, Richardson, Laura, Litvinukova, Monika, Kumasaka, Natsuhiko, Qin, Yue, Jablonska, Zuzanna, Semprich, Claudia I., Mach, Lukas, Dabrowska, Monika, Richoz, Nathan, Bolt, Liam, Mamanova, Lira, Kapuge, Rakeshlal, Barnett, Sam N., Perera, Shani, Talavera-López, Carlos, Mulas, Ilaria, Mahbubani, Krishnaa T., Tuck, Liz, Wang, Lu, Huang, Margaret M., Prete, Martin, Pritchard, Sophie, Dark, John, Saeb-Parsy, Kourosh, Patel, Minal, Clatworthy, Menna R., Hübner, Norbert, Chowdhury, Rasheda A., Noseda, Michela, and Teichmann, Sarah A.
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- 2023
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9. A spatially resolved atlas of the human lung characterizes a gland-associated immune niche
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Madissoon, Elo, Oliver, Amanda J., Kleshchevnikov, Vitalii, Wilbrey-Clark, Anna, Polanski, Krzysztof, Richoz, Nathan, Ribeiro Orsi, Ana, Mamanova, Lira, Bolt, Liam, Elmentaite, Rasa, Pett, J. Patrick, Huang, Ni, Xu, Chuan, He, Peng, Dabrowska, Monika, Pritchard, Sophie, Tuck, Liz, Prigmore, Elena, Perera, Shani, Knights, Andrew, Oszlanczi, Agnes, Hunter, Adam, Vieira, Sara F., Patel, Minal, Lindeboom, Rik G. H., Campos, Lia S., Matsuo, Kazuhiko, Nakayama, Takashi, Yoshida, Masahiro, Worlock, Kaylee B., Nikolić, Marko Z., Georgakopoulos, Nikitas, Mahbubani, Krishnaa T., Saeb-Parsy, Kourosh, Bayraktar, Omer Ali, Clatworthy, Menna R., Stegle, Oliver, Kumasaka, Natsuhiko, Teichmann, Sarah A., and Meyer, Kerstin B.
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- 2023
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10. Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer
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Li, Ruoyan, Ferdinand, John R., Loudon, Kevin W., Bowyer, Georgina S., Laidlaw, Sean, Muyas, Francesc, Mamanova, Lira, Neves, Joana B., Bolt, Liam, Fasouli, Eirini S., Lawson, Andrew R.J., Young, Matthew D., Hooks, Yvette, Oliver, Thomas R.W., Butler, Timothy M., Armitage, James N., Aho, Tev, Riddick, Antony C.P., Gnanapragasam, Vincent, Welsh, Sarah J., Meyer, Kerstin B., Warren, Anne Y., Tran, Maxine G.B., Stewart, Grant D., Cortés-Ciriano, Isidro, Behjati, Sam, Clatworthy, Menna R., Campbell, Peter J., Teichmann, Sarah A., and Mitchell, Thomas J.
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- 2022
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11. A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates
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He, Peng, Lim, Kyungtae, Sun, Dawei, Pett, Jan Patrick, Jeng, Quitz, Polanski, Krzysztof, Dong, Ziqi, Bolt, Liam, Richardson, Laura, Mamanova, Lira, Dabrowska, Monika, Wilbrey-Clark, Anna, Madissoon, Elo, Tuong, Zewen Kelvin, Dann, Emma, Suo, Chenqu, Goh, Isaac, Yoshida, Masahiro, Nikolić, Marko Z., Janes, Sam M., He, Xiaoling, Barker, Roger A., Teichmann, Sarah A., Marioni, John C., Meyer, Kerstin B., and Rawlins, Emma L.
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- 2022
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12. Local and systemic responses to SARS-CoV-2 infection in children and adults
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Yoshida, Masahiro, Worlock, Kaylee B., Huang, Ni, Lindeboom, Rik G. H., Butler, Colin R., Kumasaka, Natsuhiko, Dominguez Conde, Cecilia, Mamanova, Lira, Bolt, Liam, Richardson, Laura, Polanski, Krzysztof, Madissoon, Elo, Barnes, Josephine L., Allen-Hyttinen, Jessica, Kilich, Eliz, Jones, Brendan C., de Wilton, Angus, Wilbrey-Clark, Anna, Sungnak, Waradon, Pett, J. Patrick, Weller, Juliane, Prigmore, Elena, Yung, Henry, Mehta, Puja, Saleh, Aarash, Saigal, Anita, Chu, Vivian, Cohen, Jonathan M., Cane, Clare, Iordanidou, Aikaterini, Shibuya, Soichi, Reuschl, Ann-Kathrin, Herczeg, Iván T., Argento, A. Christine, Wunderink, Richard G., Smith, Sean B., Poor, Taylor A., Gao, Catherine A., Dematte, Jane E., Reynolds, Gary, Haniffa, Muzlifah, Bowyer, Georgina S., Coates, Matthew, Clatworthy, Menna R., Calero-Nieto, Fernando J., Göttgens, Berthold, O’Callaghan, Christopher, Sebire, Neil J., Jolly, Clare, De Coppi, Paolo, Smith, Claire M., Misharin, Alexander V., Janes, Sam M., Teichmann, Sarah A., Nikolić, Marko Z., and Meyer, Kerstin B.
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- 2022
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13. Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses
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Rodríguez-Ubreva, Javier, Arutyunyan, Anna, Bonder, Marc Jan, Del Pino-Molina, Lucía, Clark, Stephen J., de la Calle-Fabregat, Carlos, Garcia-Alonso, Luz, Handfield, Louis-François, Ciudad, Laura, Andrés-León, Eduardo, Krueger, Felix, Català-Moll, Francesc, Rodríguez-Cortez, Virginia C., Polanski, Krzysztof, Mamanova, Lira, van Dongen, Stijn, Kiselev, Vladimir Yu., Martínez-Saavedra, María T., Heyn, Holger, Martín, Javier, Warnatz, Klaus, López-Granados, Eduardo, Rodríguez-Gallego, Carlos, Stegle, Oliver, Kelsey, Gavin, Vento-Tormo, Roser, and Ballestar, Esteban
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- 2022
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14. Cells of the human intestinal tract mapped across space and time
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Elmentaite, Rasa, Kumasaka, Natsuhiko, Roberts, Kenny, Fleming, Aaron, Dann, Emma, King, Hamish W., Kleshchevnikov, Vitalii, Dabrowska, Monika, Pritchard, Sophie, Bolt, Liam, Vieira, Sara F., Mamanova, Lira, Huang, Ni, Perrone, Francesca, Goh Kai’En, Issac, Lisgo, Steven N., Katan, Matilda, Leonard, Steven, Oliver, Thomas R. W., Hook, C. Elizabeth, Nayak, Komal, Campos, Lia S., Domínguez Conde, Cecilia, Stephenson, Emily, Engelbert, Justin, Botting, Rachel A., Polanski, Krzysztof, van Dongen, Stijn, Patel, Minal, Morgan, Michael D., Marioni, John C., Bayraktar, Omer Ali, Meyer, Kerstin B., He, Xiaoling, Barker, Roger A., Uhlig, Holm H., Mahbubani, Krishnaa T., Saeb-Parsy, Kourosh, Zilbauer, Matthias, Clatworthy, Menna R., Haniffa, Muzlifah, James, Kylie R., and Teichmann, Sarah A.
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- 2021
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15. High-throughput full-length single-cell RNA-seq automation
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Mamanova, Lira, Miao, Zhichao, Jinat, Ayesha, Ellis, Peter, Shirley, Lesley, and Teichmann, Sarah A.
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- 2021
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16. Spatiotemporal immune zonation of the human kidney
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Stewart, Benjamin J., Ferdinand, John R., Young, Matthew D., Mitchell, Thomas J., Loudon, Kevin W., Riding, Alexandra M., Richoz, Nathan, Frazer, Gordon L., Staniforth, Joy U. L., Braga, Felipe A. Vieira, Botting, Rachel A., Popescu, Dorin-Mirel, Vento-Tormo, Roser, Stephenson, Emily, Cagan, Alex, Farndon, Sarah J., Polanski, Krzysztof, Efremova, Mirjana, Green, Kile, Del Castillo Velasco-Herrera, Martin, Guzzo, Charlotte, Collord, Grace, Mamanova, Lira, Aho, Tevita, Armitage, James N., Riddick, Antony C. P., Mushtaq, Imran, Farrell, Stephen, Rampling, Dyanne, Nicholson, James, Filby, Andrew, Burge, Johanna, Lisgo, Steven, Lindsay, Susan, Bajenoff, Marc, Warren, Anne Y., Stewart, Grant D., Sebire, Neil, Coleman, Nicholas, Haniffa, Muzlifah, Teichmann, Sarah A., Behjati, Sam, and Clatworthy, Menna R.
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- 2019
17. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
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Muus, Christoph, Luecken, Malte D., Eraslan, Gökcen, Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit Dhaval, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik A., Duong, Elizabeth Thu, Fiskin, Evgenij, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Buchanan, Justin, Chen, Sijia, Shu, Jian, Haber, Adam L., Chung, Hattie, Montoro, Daniel T., Adams, Taylor, Aliee, Hananeh, Allon, Samuel J., Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Bolt, Liam, Braun, Emelie, Bui, Linh T., Callori, Steven, Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas M., Cuoco, Michael S., Cuomo, Anna S. E., Deprez, Marie, Duclos, Grant, Fine, Denise, Fischer, David S., Ghazanfar, Shila, Gillich, Astrid, Giotti, Bruno, Gould, Joshua, Guo, Minzhe, Gutierrez, Austin J., Habermann, Arun C., Harvey, Tyler, He, Peng, Hou, Xiaomeng, Hu, Lijuan, Hu, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros S., Kuo, Christin S., Larsson, Ludvig, Leney-Greene, Michael A., Lim, Kyungtae, Litviňuková, Monika, Ludwig, Leif S., Lukassen, Soeren, Luo, Wendy, Maatz, Henrike, Madissoon, Elo, Mamanova, Lira, Manakongtreecheep, Kasidet, Leroy, Sylvie, Mayr, Christoph H., Mbano, Ian M., McAdams, Alexi M., Nabhan, Ahmad N., Nyquist, Sarah K., Penland, Lolita, Poirion, Olivier B., Poli, Sergio, Qi, CanCan, Queen, Rachel, Reichart, Daniel, Rosas, Ivan, Schupp, Jonas C., Shea, Conor V., Shi, Xingyi, Sinha, Rahul, Sit, Rene V., Slowikowski, Kamil, Slyper, Michal, Smith, Neal P., Sountoulidis, Alex, Strunz, Maximilian, Sullivan, Travis B., Sun, Dawei, Talavera-López, Carlos, Tan, Peng, Tantivit, Jessica, Travaglini, Kyle J., Tucker, Nathan R., Vernon, Katherine A., Wadsworth, Marc H., Waldman, Julia, Wang, Xiuting, Xu, Ke, Yan, Wenjun, Zhao, William, and Ziegler, Carly G. K.
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- 2021
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18. Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours
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Custers, Lars, Khabirova, Eleonora, Coorens, Tim H. H., Oliver, Thomas R. W., Calandrini, Camilla, Young, Matthew D., Vieira Braga, Felipe A., Ellis, Peter, Mamanova, Lira, Segers, Heidi, Maat, Arie, Kool, Marcel, Hoving, Eelco W., van den Heuvel-Eibrink, Marry M., Nicholson, James, Straathof, Karin, Hook, Liz, de Krijger, Ronald R., Trayers, Claire, Allinson, Kieren, Behjati, Sam, and Drost, Jarno
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- 2021
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19. Single cell derived mRNA signals across human kidney tumors
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Young, Matthew D., Mitchell, Thomas J., Custers, Lars, Margaritis, Thanasis, Morales-Rodriguez, Francisco, Kwakwa, Kwasi, Khabirova, Eleonora, Kildisiute, Gerda, Oliver, Thomas R. W., de Krijger, Ronald R., van den Heuvel-Eibrink, Marry M., Comitani, Federico, Piapi, Alice, Bugallo-Blanco, Eva, Thevanesan, Christine, Burke, Christina, Prigmore, Elena, Ambridge, Kirsty, Roberts, Kenny, Braga, Felipe A. Vieira, Coorens, Tim H. H., Del Valle, Ignacio, Wilbrey-Clark, Anna, Mamanova, Lira, Stewart, Grant D., Gnanapragasam, Vincent J., Rampling, Dyanne, Sebire, Neil, Coleman, Nicholas, Hook, Liz, Warren, Anne, Haniffa, Muzlifah, Kool, Marcel, Pfister, Stefan M., Achermann, John C., He, Xiaoling, Barker, Roger A., Shlien, Adam, Bayraktar, Omer A., Teichmann, Sarah A., Holstege, Frank C., Meyer, Kerstin B., Drost, Jarno, Straathof, Karin, and Behjati, Sam
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- 2021
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20. MultiMAP: dimensionality reduction and integration of multimodal data
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Jain, Mika Sarkin, Polanski, Krzysztof, Conde, Cecilia Dominguez, Chen, Xi, Park, Jongeun, Mamanova, Lira, Knights, Andrew, Botting, Rachel A., Stephenson, Emily, Haniffa, Muzlifah, Lamacraft, Austen, Efremova, Mirjana, and Teichmann, Sarah A.
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- 2021
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21. Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors
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Young, Matthew D., Mitchell, Thomas J., Braga, Felipe A. Vieira, Tran, Maxine G. B., Stewart, Benjamin J., Ferdinand, John R., Collord, Grace, Botting, Rachel A., Popescu, Dorin-Mirel, Loudon, Kevin W., Vento-Tormo, Roser, Stephenson, Emily, Cagan, Alex, Farndon, Sarah J., Del Castillo Velasco-Herrera, Martin, Guzzo, Charlotte, Richoz, Nathan, Mamanova, Lira, Aho, Tevita, Armitage, James N., Riddick, Antony C. P., Mushtaq, Imran, Farrell, Stephen, Rampling, Dyanne, Nicholson, James, Filby, Andrew, Burge, Johanna, Lisgo, Steven, Maxwell, Patrick H., Lindsay, Susan, Warren, Anne Y., Stewart, Grant D., Sebire, Neil, Coleman, Nicholas, Haniffa, Muzlifah, Teichmann, Sarah A., Clatworthy, Menna, and Behjati, Sam
- Published
- 2018
22. Decoding human fetal liver haematopoiesis
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Popescu, Dorin-Mirel, Botting, Rachel A., Stephenson, Emily, Green, Kile, Webb, Simone, Jardine, Laura, Calderbank, Emily F., Polanski, Krzysztof, Goh, Issac, Efremova, Mirjana, Acres, Meghan, Maunder, Daniel, Vegh, Peter, Gitton, Yorick, Park, Jong-Eun, Vento-Tormo, Roser, Miao, Zhichao, Dixon, David, Rowell, Rachel, McDonald, David, Fletcher, James, Poyner, Elizabeth, Reynolds, Gary, Mather, Michael, Moldovan, Corina, Mamanova, Lira, Greig, Frankie, Young, Matthew D., Meyer, Kerstin B., Lisgo, Steven, Bacardit, Jaume, Fuller, Andrew, Millar, Ben, Innes, Barbara, Lindsay, Susan, Stubbington, Michael J. T., Kowalczyk, Monika S., Li, Bo, Ashenberg, Orr, Tabaka, Marcin, Dionne, Danielle, Tickle, Timothy L., Slyper, Michal, Rozenblatt-Rosen, Orit, Filby, Andrew, Carey, Peter, Villani, Alexandra-Chloé, Roy, Anindita, Regev, Aviv, Chédotal, Alain, Roberts, Irene, Göttgens, Berthold, Behjati, Sam, Laurenti, Elisa, Teichmann, Sarah A., and Haniffa, Muzlifah
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- 2019
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23. Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis
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Penkava, Frank, Velasco-Herrera, Martin Del Castillo, Young, Matthew D., Yager, Nicole, Nwosu, Lilian N., Pratt, Arthur G., Lara, Alicia Lledo, Guzzo, Charlotte, Maroof, Ash, Mamanova, Lira, Cole, Suzanne, Efremova, Mirjana, Simone, Davide, Filer, Andrew, Brown, Chrysothemis C., Croxford, Andrew L., Isaacs, John D., Teichmann, Sarah, Bowness, Paul, Behjati, Sam, and Hussein Al-Mossawi, M.
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- 2020
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24. BraCeR: B-cell-receptor reconstruction and clonality inference from single-cell RNA-seq
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Lindeman, Ida, Emerton, Guy, Mamanova, Lira, Snir, Omri, Polanski, Krzysztof, Qiao, Shuo-Wang, Sollid, Ludvig M., Teichmann, Sarah A., and Stubbington, Michael J. T.
- Published
- 2018
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25. Early human lung immune cell development and its role in epithelial cell fate.
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Barnes, Josephine L., Yoshida, Masahiro, He, Peng, Worlock, Kaylee B., Lindeboom, Rik G.H., Suo, Chenqu, Pett, J. Patrick, Wilbrey-Clark, Anna, Dann, Emma, Mamanova, Lira, Richardson, Laura, Polanski, Krzysztof, Pennycuick, Adam, Allen-Hyttinen, Jessica, Herczeg, Iván T., Arzili, Romina, Hynds, Robert E., Teixeira, Vitor H., Haniffa, Muzlifah, and Lim, Kyungtae
- Subjects
EPITHELIAL cells ,KILLER cells ,MYELOID cells ,LUNG development ,INNATE lymphoid cells ,TALL-1 (Protein) ,METHACHOLINE chloride - Abstract
Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1β drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1β–producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development. Editor's summary: From birth, the airways provide protection against respiratory pathogens and inhaled toxins, but little is known about the early development of lung immune cells. Using single cell transcriptomics, Barnes et al. characterized human embryonic and fetal immune cells in the developing lungs between 5 and 22 weeks post-conception. All stages of B cell development were detected, including mature B-1-like cells, suggesting that fetal lungs provide a local niche for B cell maturation. Myeloid cells were widespread, including near epithelial tips, and produced IL-1β, which induced epithelial stem cell differentiation into basal cells within fetal lung organoids. Together, these findings provide an immune atlas of developing human lungs and suggest a role for fetal immune cells in guiding development of the lung epithelium. —Claire Olingy [ABSTRACT FROM AUTHOR]
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- 2023
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26. Exploration of signals of positive selection derived from genotype-based human genome scans using re-sequencing data
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Hu, Min, Ayub, Qasim, Guerra-Assunção, José Afonso, Long, Quan, Ning, Zemin, Huang, Ni, Romero, Irene Gallego, Mamanova, Lira, Akan, Pelin, Liu, Xin, Coffey, Alison J., Turner, Daniel J., Swerdlow, Harold, Burton, John, Quail, Michael A., Conrad, Donald F., Enright, Anton J., Tyler-Smith, Chris, and Xue, Yali
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- 2012
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27. A comparison of key aspects of gene regulation in Streptomyces coelicolor and Escherichia coli using nucleotide-resolution transcription maps produced in parallel by global and differential RNA sequencing
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Romero, David A., Hasan, Ayad H., Lin, Yu-fei, Kime, Louise, Ruiz-Larrabeiti, Olatz, Urem, Mia, Bucca, Giselda, Mamanova, Lira, Laing, Emma E., van Wezel, Gilles P., Smith, Colin P., Kaberdin, Vladimir R., and McDowall, Kenneth J.
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- 2014
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28. Cellular mRNA signals in human kidney tumors
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Young, Matthew D, Mitchell, Thomas J, Custers, Lars MC, Khabirova, Eleonora, Oliver, Thomas RW, Comitani, Federico, Piapi, Alice, Blanco, Eva Bugallo, Thevanesan, Christine, Roberts, Kenny, Braga, Felipe A Vieira, Coorens, Tim HH, Del Valle, Ignacio, Wilbrey-Clark, Anna, Mamanova, Lira, Stewart, Grant D, Gnagapragasam, Vincent J, Rampling, Dyanne, Sebire, Neil, Coleman, Nicholas, Hook, Liz, Warren, Anne, Haniffa, Muzlifah, Kool, Marcel, Pfister, Stefan M, Achermann, John C, He, Xiaoling, Barker, Roger A, Shlien, Adam, Bayraktar, Omer A, Teichmann, Sarah, Meyer, Kerstin B, Drost, Jarno, Straathof, Karin, and Behjati, Sam
- Abstract
Tumor cells may produce many of the same messenger RNAs (mRNA) as the cell they derive from. The relative abundance of these mRNAs, the transcriptiomic profile, may provide clues into the origin and development of tumors. Here we investigated the cellular origins of 1,300 childhood and adult renal tumors, spanning 7 different subtypes. We decomposed tumor bulk transcriptomes into single cell components, measuring the abundance of single cell derived reference “cellular signals” in each tumor. We quantified the extent to which each tumor utilized fetal cellular signals, finding that all childhood renal tumors are definitively fetal. This replaces the long-held presumption of “fetalness” with a precise, quantitative readout of immaturity. Analyzing cellular signals in each tumor type, we recapitulated previous findings for some, whilst providing novel insights into other, less well understood tumor types. For example, our analyses predicted fetal interstitial cells as the cell of origin of the infant kidney tumor, congenital mesoblastic nephroma, and demonstrate that another childhood kidney cancer, malignant rhabdoid tumor, arises from mesodermally derived cells in early development. We found remarkable uniformity in the cell signal of each tumor type, indicating the possible therapeutic and diagnostic utility of cellular signal decomposition. We demonstrated this utility with an example of a child with a cryptic renal tumor, which had not been identifiable by conventional diagnostic work-up but was clearly classified with our approach. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.
- Published
- 2020
- Full Text
- View/download PDF
29. Characterization of High-Altitude Pulmonary Hypertension in the Kyrgyz: Association with Angiotensin-Converting Enzyme Genotype
- Author
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Aldashev, Almaz A., Sarybaev, Akpay S., Sydykov, Akyl S., Kalmyrzaev, Bolot B., Kim, Elena V., Mamanova, Lira B., Maripov, Rashid, Kojonazarov, Baktybek K., Mirrakhimov, Mirsaid M., Wilkins, Martin R., and Morrell, Nicholas W.
- Published
- 2002
- Full Text
- View/download PDF
30. Mapping Rora expression in resting and activated CD4+ T cells.
- Author
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Haim-Vilmovsky, Liora, Henriksson, Johan, Walker, Jennifer A., Miao, Zhichao, Natan, Eviatar, Kar, Gozde, Clare, Simon, Barlow, Jillian L., Charidemou, Evelina, Mamanova, Lira, Chen, Xi, Proserpio, Valentina, Pramanik, Jhuma, Woodhouse, Steven, Protasio, Anna V., Efremova, Mirjana, Griffin, Julian L., Berriman, Matt, Dougan, Gordon, and Fisher, Jasmin
- Subjects
T cells ,REGULATORY T cells ,TH2 cells ,PNEUMONIA ,TRANSCRIPTION factors - Abstract
The transcription factor Rora has been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role of Rora across CD4+ T cells in general, but with an emphasis on Th2 cells, both in vitro as well as in the context of several in vivo type 2 infection models. We dissect the function of Rora using overexpression and a CD4-conditional Rora-knockout mouse, as well as a RORA-reporter mouse. We establish the importance of Rora in CD4+ T cells for controlling lung inflammation induced by Nippostrongylus brasiliensis infection, and have measured the effect on downstream genes using RNA-seq. Using a systematic stimulation screen of CD4+ T cells, coupled with RNA-seq, we identify upstream regulators of Rora, most importantly IL-33 and CCL7. Our data suggest that Rora is a negative regulator of the immune system, possibly through several downstream pathways, and is under control of the local microenvironment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
31. Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer.
- Author
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Shlien, Adam, Raine, Keiran, Fuligni, Fabio, Arnold, Roland, Nik-Zainal, Serena, Dronov, Serge, Mamanova, Lira, Rosic, Andrej, Ju, Young Seok, Cooke, Susanna L., Ramakrishna, Manasa, Papaemmanuil, Elli, Davies, Helen R., Tarpey, Patrick S., Van Loo, Peter, Wedge, David C., Jones, David R., Martin, Sancha, Marshall, John, and Anderson, Elizabeth
- Abstract
Summary Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER)-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
32. A comparison of key aspects of gene regulation in S treptomyces coelicolor and E scherichia coli using nucleotide-resolution transcription maps produced in parallel by global and differential RNA sequencing.
- Author
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Romero, David A., Hasan, Ayad H., Lin, Yu‐fei, Kime, Louise, Ruiz‐Larrabeiti, Olatz, Urem, Mia, Bucca, Giselda, Mamanova, Lira, Laing, Emma E., Wezel, Gilles P., Smith, Colin P., Kaberdin, Vladimir R., and McDowall, Kenneth J.
- Subjects
STREPTOMYCES coelicolor ,BACTERIAL physiology ,GENETICS ,TRANSCRIPTION factors ,RNA sequencing - Abstract
S treptomyces coelicolor is a model for studying bacteria renowned as the foremost source of natural products used clinically. Post-genomic studies have revealed complex patterns of gene expression and links to growth, morphological development and individual genes. However, the underlying regulation remains largely obscure, but undoubtedly involves steps after transcription initiation. Here we identify sites involved in RNA processing and degradation as well as transcription within a nucleotide-resolution map of the transcriptional landscape. This was achieved by combining RNA-sequencing approaches suited to the analysis of GC-rich organisms. E scherichia coli was analysed in parallel to validate the methodology and allow comparison. Previously, sites of RNA processing and degradation had not been mapped on a transcriptome-wide scale for E . coli. Through examples, we show the value of our approach and data sets. This includes the identification of new layers of transcriptional complexity associated with several key regulators of secondary metabolism and morphological development in S . coelicolor and the identification of host-encoded leaderless mRNA and rRNA processing associated with the generation of specialized ribosomes in E . coli. New regulatory small RNAs were identified for both organisms. Overall the results illustrate the diversity in mechanisms used by different bacterial groups to facilitate and regulate gene expression. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
33. A combination of improved differential and global RNA-seq reveals pervasive transcription initiation and events in all stages of the life-cycle of functional RNAs in Propionibacterium acnes, a major contributor to wide-spread human disease.
- Author
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Yu-fei Lin, David Romero, A., Shuang Guan, Mamanova, Lira, and McDowall, Kenneth J.
- Subjects
GENETIC regulation ,NUCLEIC acids ,MESSENGER RNA ,TRANSFER RNA ,GENE expression - Abstract
Background: Sequencing of the genome of Propionibacterium acnes produced a catalogue of genes many of which enable this organism to colonise skin and survive exposure to the elements. Despite this platform, there was little understanding of the gene regulation that gives rise to an organism that has a major impact on human health and wellbeing and causes infections beyond the skin. To address this situation, we have undertaken a genome- wide study of gene regulation using a combination of improved differential and global RNA-sequencing and an analytical approach that takes into account the inherent noise within the data. Results: We have produced nucleotide-resolution transcriptome maps that identify and differentiate sites of transcription initiation from sites of stable RNA processing and mRNA cleavage. Moreover, analysis of these maps provides strong evidence for 'pervasive' transcription and shows that contrary to initial indications it is not biased towards the production of antisense RNAs. In addition, the maps reveal an extensive array of riboswitches, leaderless mRNAs and small non-protein-coding RNAs alongside vegetative promoters and post-transcriptional events, which includes unusual tRNA processing. The identification of such features will inform models of complex gene regulation, as illustrated here for ribonucleotide reductases and a potential quorum-sensing, two-component system. Conclusions: The approach described here, which is transferable to any bacterial species, has produced a step increase in whole-cell knowledge of gene regulation in P. acnes. Continued expansion of our maps to include transcription associated with different growth conditions and genetic backgrounds will provide a new platform from which to computationally model the gene expression that determines the physiology of P. acnes and its role in human disease. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
34. Mutation spectrum revealed by breakpoint sequencing of human germline CNVs.
- Author
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Conrad, Donald F., Bird, Christine, Blackburne, Ben, Lindsay, Sarah, Mamanova, Lira, Lee, Charles, Turner, Daniel J., and Hurles, Matthew E.
- Subjects
GERM cells ,NUCLEOTIDE sequence ,GENETIC code ,GENETIC transcription ,GENETIC translation ,BIOCHEMICAL genetics - Abstract
Precisely characterizing the breakpoints of copy number variants (CNVs) is crucial for assessing their functional impact. However, fewer than 10% of known germline CNVs have been mapped to the single-nucleotide level. We characterized the sequence breakpoints from a dataset of all CNVs detected in three unrelated individuals in previous array-based CNV discovery experiments. We used targeted hybridization-based DNA capture and 454 sequencing to sequence 324 CNV breakpoints, including 315 deletions. We observed two major breakpoint signatures: 70% of the deletion breakpoints have 1−30 bp of microhomology, whereas 33% of deletion breakpoints contain 1−367 bp of inserted sequence. The co-occurrence of microhomology and inserted sequence is low (10%), suggesting that there are at least two different mutational mechanisms. Approximately 5% of the breakpoints represent more complex rearrangements, including local microinversions, suggesting a replication-based strand switching mechanism. Despite a rich literature on DNA repair processes, reconstruction of the molecular events generating each of these mutations is not yet possible. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
35. Target-enrichment strategies for next-generation sequencing.
- Author
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Mamanova, Lira, Coffey, Alison J., Scott, Carol E., Kozarewa, Iwanka, Turner, Emily H., Kumar, Akash, Howard, Eleanor, Shendure, Jay, and Turner, Daniel J.
- Subjects
- *
GENOMES , *EUKARYOTIC cells , *MEDICAL protocols , *DNA , *GENETICS - Abstract
We have not yet reached a point at which routine sequencing of large numbers of whole eukaryotic genomes is feasible, and so it is often necessary to select genomic regions of interest and to enrich these regions before sequencing. There are several enrichment approaches, each with unique advantages and disadvantages. Here we describe our experiences with the leading target-enrichment technologies, the optimizations that we have performed and typical results that can be obtained using each. We also provide detailed protocols for each technology so that end users can find the best compromise between sensitivity, specificity and uniformity for their particular project. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
36. FRT-seq: amplification-free, strand-specific transcriptome sequencing.
- Author
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Mamanova, Lira, Andrews, Robert M., James, Keith D., Sheridan, Elizabeth M., Ellis, Peter D., Langford, Cordelia F., Ost, Tobias W. B., Collins, John E., and Turner, Daniel J.
- Subjects
- *
RNA , *DNA , *GENOMES , *GENE amplification , *NUCLEIC acids , *RIBOSE - Abstract
We report an alternative approach to transcriptome sequencing for the Illumina Genome Analyzer, in which the reverse transcription reaction takes place on the flowcell. No amplification is performed during the library preparation, so PCR biases and duplicates are avoided, and because the template is poly(A)+ RNA rather than cDNA, the resulting sequences are necessarily strand-specific. The method is compatible with paired- or single-end sequencing. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
37. Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell.
- Author
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Kildisiute, Gerda, Kholosy, Waleed M., Young, Matthew D., Roberts, Kenny, Elmentaite, Rasa, van Hooff, Sander R., Pacyna, Clarissa N., Khabirova, Eleonora, Piapi, Alice, Thevanesan, Christine, Bugallo-Blanco, Eva, Burke, Christina, Mamanova, Lira, Keller, Kaylee M., Langenberg-Ververgaert, Karin P. S., Lijnzaad, Philip, Margaritis, Thanasis, Holstege, Frank C. P., Tas, Michelle L., and Wijnen, Marc H. W. A.
- Subjects
- *
CANCER cells , *PLANT chromosomes , *FETAL heart , *HUMAN biology , *GENETIC mutation , *HUMAN genetic variation , *MESSENGER RNA , *NEGATIVE binomial distribution - Abstract
The article discusses neuroblastoma has a childhood cancer that resembles developmental stages of the neural crest and has not established what developmental processes neuroblastoma cancer cells represent. Topics include the sympathoblastic state has a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes; and advances in single-cell transcriptomics have enabled the direct comparison of cancer and normal reference cells.
- Published
- 2021
- Full Text
- View/download PDF
38. Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age.
- Author
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Wells SB, Rainbow DB, Mark M, Szabo PA, Ergen C, Maceiras AR, Caron DP, Rahmani E, Benuck E, Amiri VVP, Chen D, Wagner A, Howlett SK, Jarvis LB, Ellis KL, Kubota M, Matsumoto R, Mahbubani K, Saeb-Parsy K, Dominguez-Conde C, Richardson L, Xu C, Li S, Mamanova L, Bolt L, Wilk A, Teichmann SA, Farber DL, Sims PA, Jones JL, and Yosef N
- Abstract
The immune system comprises multiple cell lineages and heterogeneous subsets found in blood and tissues throughout the body. While human immune responses differ between sites and over age, the underlying sources of variation remain unclear as most studies are limited to peripheral blood. Here, we took a systems approach to comprehensively profile RNA and surface protein expression of over 1.25 million immune cells isolated from blood, lymphoid organs, and mucosal tissues of 24 organ donors aged 20-75 years. We applied a multimodal classifier to annotate the major immune cell lineages (T cells, B cells, innate lymphoid cells, and myeloid cells) and their corresponding subsets across the body, leveraging probabilistic modeling to define bases for immune variations across donors, tissue, and age. We identified dominant tissue-specific effects on immune cell composition and function across lineages for lymphoid sites, intestines, and blood-rich tissues. Age-associated effects were intrinsic to both lineage and site as manifested by macrophages in mucosal sites, B cells in lymphoid organs, and T and NK cells in blood-rich sites. Our results reveal tissue-specific signatures of immune homeostasis throughout the body and across different ages. This information provides a basis for defining the transcriptional underpinnings of immune variation and potential associations with disease-associated immune pathologies across the human lifespan.
- Published
- 2024
- Full Text
- View/download PDF
39. A cell atlas of human thymic development defines T cell repertoire formation.
- Author
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Park JE, Botting RA, Domínguez Conde C, Popescu DM, Lavaert M, Kunz DJ, Goh I, Stephenson E, Ragazzini R, Tuck E, Wilbrey-Clark A, Roberts K, Kedlian VR, Ferdinand JR, He X, Webb S, Maunder D, Vandamme N, Mahbubani KT, Polanski K, Mamanova L, Bolt L, Crossland D, de Rita F, Fuller A, Filby A, Reynolds G, Dixon D, Saeb-Parsy K, Lisgo S, Henderson D, Vento-Tormo R, Bayraktar OA, Barker RA, Meyer KB, Saeys Y, Bonfanti P, Behjati S, Clatworthy MR, Taghon T, Haniffa M, and Teichmann SA
- Subjects
- CD8-Positive T-Lymphocytes cytology, Dendritic Cells cytology, Dendritic Cells immunology, Fibroblasts cytology, Fibroblasts immunology, Humans, RNA-Seq methods, Receptors, Antigen, T-Cell metabolism, Single-Cell Analysis methods, Thymus Gland cytology, Atlases as Topic, CD8-Positive T-Lymphocytes immunology, Cell Differentiation, Thymus Gland growth & development, Thymus Gland immunology
- Abstract
The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8αα
+ T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2020
- Full Text
- View/download PDF
40. Setting Up a Single-Cell Genomic Laboratory.
- Author
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Mamanova L
- Subjects
- Equipment Design, Gene Expression Profiling instrumentation, Genome, Humans, Laboratories, Quality Control, Sequence Analysis, RNA instrumentation, Single-Cell Analysis instrumentation, Specimen Handling methods, Gene Expression Profiling methods, RNA genetics, Sequence Analysis, RNA methods, Single-Cell Analysis methods
- Abstract
Transcriptomics has been revolutionized by massive throughput RNA-seq. To date, the ongoing decrease in sequencing cost and recent eruption of single-cell related protocols have boosted a demand for single-cell RNA sequencing projects. Although the single-cell RNA-Seq (scRNA-Seq) approach is close to the conventional "bulk" RNA-seq, several features that are unique to scRNA-seq should be taken into consideration in order to obtain high-quality libraries and unbiased sequencing data.In this chapter I give recommendations for setting up the single cell-suitable laboratory environment.
- Published
- 2019
- Full Text
- View/download PDF
41. Low-bias, strand-specific transcriptome Illumina sequencing by on-flowcell reverse transcription (FRT-seq).
- Author
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Mamanova L and Turner DJ
- Subjects
- Base Sequence, Chromosome Mapping methods, Fluorescence Resonance Energy Transfer methods, Gene Expression Profiling methods, Nucleic Acid Amplification Techniques methods, RNA, Messenger chemistry, Reverse Transcription
- Abstract
The unifying feature of second-generation sequencing technologies is that single template strands are amplified clonally onto a solid surface prior to the sequencing reaction. To convert template strands into a compatible state for attachment to this surface, a multistep library preparation is required, which typically culminates in amplification by the PCR. PCR is an inherently biased process, which decreases the efficiency of data acquisition. Flowcell reverse transcription sequencing is a method of transcriptome sequencing for Illumina sequencers in which the reverse transcription reaction is performed on the flowcell by using unamplified, adapter-ligated mRNA as a template. This approach removes PCR biases and duplicates, generates strand-specific paired-end data and is highly reproducible. The procedure can be performed quickly, taking 2 d to generate clusters from mRNA.
- Published
- 2011
- Full Text
- View/download PDF
42. Genome-wide scan for premature hypertension supports linkage to chromosome 2 in a large Kyrgyz family.
- Author
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Kalmyrzaev B, Aldashev A, Khalmatov M, Polupanov A, Jumagulova A, Mamanova L, Wilkins MR, and Town M
- Subjects
- Adult, Early Diagnosis, Genetic Markers, Humans, Kyrgyzstan, Middle Aged, Chromosomes, Human, Pair 2 genetics, Genetic Linkage, Genome, Human, Hypertension diagnosis, Hypertension genetics, Pedigree
- Abstract
We report a genome-wide scan for susceptibility loci to hypertension in a single Kyrgyz family where 10 of the affected relatives developed hypertension before the age of 35 years, and some members have suffered stroke. The early onset of disease and the geographic isolation of the Kyrgyz population are both expected to select for an increased influence of genetic factors in hypertension. We genotyped 44 individuals from this Krygyz family with 374 microsatellite markers, covering a 10-centimorgan map. Nonparametric analysis suggests that affected status is linked to loci in the chromosome 2q23 to q37 genomic interval, whereas 2-point parametric analysis returned a logarithm of odds score of 2.67 for marker D2S2330 (2q24.3). Multipoint linkage analysis substantiated the evidence for a hypertension susceptibility allele in the chromosome 2q23 to q36 region. Fine mapping and haplotype analysis implicate that the genetic lesion resides between markers D2S2380 (166.5 cM) and D2S335 (175.9 cM). This finding supports other recent studies of early onset hypertension suggesting that the region 2q24.3 to q31.1 encompasses a novel locus for premature hypertension.
- Published
- 2006
- Full Text
- View/download PDF
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