Search

Your search keyword '"Winteringham L"' showing total 10 results
Start Over Author "Winteringham L"
10 results on '"Winteringham L"'

1. Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Author

Grapotte M., Saraswat M., Bessiere C., Menichelli C., Ramilowski J. A., Severin J., Hayashizaki Y., Itoh M., Tagami M., Murata M., Kojima-Ishiyama M., Noma S., Noguchi S., Kasukawa T., Hasegawa A., Suzuki H., Nishiyori-Sueki H., Frith M. C., Abugessaisa I., Aitken S., Aken B. L., Alam I., Alam T., Alasiri R., Alhendi A. M. N., Alinejad-Rokny H., Alvarez M. J., Andersson R., Arakawa T., Araki M., Arbel T., Archer J., Archibald A. L., Arner E., Arner P., Asai K., Ashoor H., Astrom G., Babina M., Baillie J. K., Bajic V. B., Bajpai A., Baker S., Baldarelli R. M., Balic A., Bansal M., Batagov A. O., Batzoglou S., Beckhouse A. G., Beltrami A. P., Beltrami C. A., Bertin N., Bhattacharya S., Bickel P. J., Blake J. A., Blanchette M., Bodega B., Bonetti A., Bono H., Bornholdt J., Bttcher M., Bougouffa S., Boyd M., Breda J., Brombacher F., Brown J. B., Bult C. J., Burroughs A. M., Burt D. W., Busch A., Caglio G., Califano A., Cameron C. J., Cannistraci C. V., Carbone A., Carlisle A. J., Carninci P., Carter K. W., Cesselli D., Chang J. -C., Chen J. C., Chen Y., Chierici M., Christodoulou J., Ciani Y., Clark E. L., Coskun M., Dalby M., Dalla E., Daub C. O., Davis C. A., de Hoon M. J. L., de Rie D., Denisenko E., Deplancke B., Detmar M., Deviatiiarov R., Di Bernardo D., Diehl A. D., Dieterich L. C., Dimont E., Djebali S., Dohi T., Dostie J., Drablos F., Edge A. S. B., Edinger M., Ehrlund A., Ekwall K., Elofsson A., Endoh M., Enomoto H., Enomoto S., Faghihi M., Fagiolini M., Farach-Carson M. C., Faulkner G. J., Favorov A., Fernandes A. M., Ferrai C., Forrest A. R. R., Forrester L. M., Forsberg M., Fort A., Francescatto M., Freeman T. C., Frith M., Fukuda S., Funayama M., Furlanello C., Furuno M., Furusawa C., Gao H., Gazova I., Gebhard C., Geier F., Geijtenbeek T. B. H., Ghosh S., Ghosheh Y., Gingeras T. R., Gojobori T., Goldberg T., Goldowitz D., Gough J., Greco D., Gruber A. J., Guhl S., Guigo R., Guler R., Gusev O., Gustincich S., Ha T. J., Haberle V., Hale P., Hallstrom B. M., Hamada M., Handoko L., Hara M., Harbers M., Harrow J., Harshbarger J., Hase T., Hashimoto K., Hatano T., Hattori N., Hayashi R., Herlyn M., Hettne K., Heutink P., Hide W., Hitchens K. J., Sui S. H., 't Hoen P. A. C., Hon C. C., Hori F., Horie M., Horimoto K., Horton P., Hou R., Huang E., Huang Y., Hugues R., Hume D., Ienasescu H., Iida K., Ikawa T., Ikemura T., Ikeo K., Inoue N., Ishizu Y., Ito Y., Ivshina A. V., Jankovic B. R., Jenjaroenpun P., Johnson R., Jorgensen M., Jorjani H., Joshi A., Jurman G., Kaczkowski B., Kai C., Kaida K., Kajiyama K., Kaliyaperumal R., Kaminuma E., Kanaya T., Kaneda H., Kapranov P., Kasianov A. S., Katayama T., Kato S., Kawaguchi S., Kawai J., Kawaji H., Kawamoto H., Kawamura Y. I., Kawasaki S., Kawashima T., Kempfle J. S., Kenna T. J., Kere J., Khachigian L., Kiryu H., Kishima M., Kitajima H., Kitamura T., Kitano H., Klaric E., Klepper K., Klinken S. P., Kloppmann E., Knox A. J., Kodama Y., Kogo Y., Kojima M., Kojima S., Komatsu N., Komiyama H., Kono T., Koseki H., Koyasu S., Kratz A., Kukalev A., Kulakovskiy I., Kundaje A., Kunikata H., Kuo R., Kuo T., Kuraku S., Kuznetsov V. A., Kwon T. J., Larouche M., Lassmann T., Law A., Le-Cao K. -A., Lecellier C. -H., Lee W., Lenhard B., Lennartsson A., Li K., Li R., Lilje B., Lipovich L., Lizio M., Lopez G., Magi S., Mak G. K., Makeev V., Manabe R., Mandai M., Mar J., Maruyama K., Maruyama T., Mason E., Mathelier A., Matsuda H., Medvedeva Y. A., Meehan T. F., Mejhert N., Meynert A., Mikami N., Minoda A., Miura H., Miyagi Y., Miyawaki A., Mizuno Y., Morikawa H., Morimoto M., Morioka M., Morishita S., Moro K., Motakis E., Motohashi H., Mukarram A. K., Mummery C. L., Mungall C. J., Murakawa Y., Muramatsu M., Nagasaka K., Nagase T., Nakachi Y., Nakahara F., Nakai K., Nakamura K., Nakamura Y., Nakazawa T., Nason G. P., Nepal C., Nguyen Q. H., Nielsen L. K., Nishida K., Nishiguchi K. M., Nishiyori H., Nitta K., Notredame C., Ogishima S., Ohkura N., Ohno H., Ohshima M., Ohtsu T., Okada Y., Okada-Hatakeyama M., Okazaki Y., Oksvold P., Orlando V., Ow G. S., Ozturk M., Pachkov M., Paparountas T., Parihar S. P., Park S. -J., Pascarella G., Passier R., Persson H., Philippens I. H., Piazza S., Plessy C., Pombo A., Ponten F., Poulain S., Poulsen T. M., Pradhan S., Prezioso C., Pridans C., Qin X. -Y., Quackenbush J., Rackham O., Ramilowski J., Ravasi T., Rehli M., Rennie S., Rito T., Rizzu P., Robert C., Roos M., Rost B., Roudnicky F., Roy R., Rye M. B., Sachenkova O., Saetrom P., Sai H., Saiki S., Saito M., Saito A., Sakaguchi S., Sakai M., Sakaue S., Sakaue-Sawano A., Sandelin A., Sano H., Sasamoto Y., Sato H., Saxena A., Saya H., Schafferhans A., Schmeier S., Schmidl C., Schmocker D., Schneider C., Schueler M., Schultes E. A., Schulze-Tanzil G., Semple C. A., Seno S., Seo W., Sese J., Sheng G., Shi J., Shimoni Y., Shin J. W., SimonSanchez J., Sivertsson A., Sjostedt E., Soderhall C., Laurent G. S., Stoiber M. H., Sugiyama D., Summers K. M., Suzuki A. M., Suzuki K., Suzuki M., Suzuki N., Suzuki T., Swanson D. J., Swoboda R. K., Taguchi A., Takahashi H., Takahashi M., Takamochi K., Takeda S., Takenaka Y., Tam K. T., Tanaka H., Tanaka R., Tanaka Y., Tang D., Taniuchi I., Tanzer A., Tarui H., Taylor M. S., Terada A., Terao Y., Testa A. C., Thomas M., Thongjuea S., Tomii K., Triglia E. T., Toyoda H., Tsang H. G., Tsujikawa M., Uhlen M., Valen E., van de Wetering M., van Nimwegen E., Velmeshev D., Verardo R., Vitezic M., Vitting-Seerup K., von Feilitzen K., Voolstra C. R., Vorontsov I. E., Wahlestedt C., Wasserman W. W., Watanabe K., Watanabe S., Wells C. A., Winteringham L. N., Wolvetang E., Yabukami H., Yagi K., Yamada T., Yamaguchi Y., Yamamoto M., Yamamoto Y., Yamanaka Y., Yano K., Yasuzawa K., Yatsuka Y., Yo M., Yokokura S., Yoneda M., Yoshida E., Yoshida Y., Yoshihara M., Young R., Young R. S., Yu N. Y., Yumoto N., Zabierowski S. E., Zhang P. G., Zucchelli S., Zwahlen M., Chatelain C., Brehelin L., Grapotte, M., Saraswat, M., Bessiere, C., Menichelli, C., Ramilowski, J. A., Severin, J., Hayashizaki, Y., Itoh, M., Tagami, M., Murata, M., Kojima-Ishiyama, M., Noma, S., Noguchi, S., Kasukawa, T., Hasegawa, A., Suzuki, H., Nishiyori-Sueki, H., Frith, M. C., Abugessaisa, I., Aitken, S., Aken, B. L., Alam, I., Alam, T., Alasiri, R., Alhendi, A. M. N., Alinejad-Rokny, H., Alvarez, M. J., Andersson, R., Arakawa, T., Araki, M., Arbel, T., Archer, J., Archibald, A. L., Arner, E., Arner, P., Asai, K., Ashoor, H., Astrom, G., Babina, M., Baillie, J. K., Bajic, V. B., Bajpai, A., Baker, S., Baldarelli, R. M., Balic, A., Bansal, M., Batagov, A. O., Batzoglou, S., Beckhouse, A. G., Beltrami, A. P., Beltrami, C. A., Bertin, N., Bhattacharya, S., Bickel, P. J., Blake, J. A., Blanchette, M., Bodega, B., Bonetti, A., Bono, H., Bornholdt, J., Bttcher, M., Bougouffa, S., Boyd, M., Breda, J., Brombacher, F., Brown, J. B., Bult, C. J., Burroughs, A. M., Burt, D. W., Busch, A., Caglio, G., Califano, A., Cameron, C. J., Cannistraci, C. V., Carbone, A., Carlisle, A. J., Carninci, P., Carter, K. W., Cesselli, D., Chang, J. -C., Chen, J. C., Chen, Y., Chierici, M., Christodoulou, J., Ciani, Y., Clark, E. L., Coskun, M., Dalby, M., Dalla, E., Daub, C. O., Davis, C. A., de Hoon, M. J. L., de Rie, D., Denisenko, E., Deplancke, B., Detmar, M., Deviatiiarov, R., Di Bernardo, D., Diehl, A. D., Dieterich, L. C., Dimont, E., Djebali, S., Dohi, T., Dostie, J., Drablos, F., Edge, A. S. B., Edinger, M., Ehrlund, A., Ekwall, K., Elofsson, A., Endoh, M., Enomoto, H., Enomoto, S., Faghihi, M., Fagiolini, M., Farach-Carson, M. C., Faulkner, G. J., Favorov, A., Fernandes, A. M., Ferrai, C., Forrest, A. R. R., Forrester, L. M., Forsberg, M., Fort, A., Francescatto, M., Freeman, T. C., Frith, M., Fukuda, S., Funayama, M., Furlanello, C., Furuno, M., Furusawa, C., Gao, H., Gazova, I., Gebhard, C., Geier, F., Geijtenbeek, T. B. H., Ghosh, S., Ghosheh, Y., Gingeras, T. R., Gojobori, T., Goldberg, T., Goldowitz, D., Gough, J., Greco, D., Gruber, A. J., Guhl, S., Guigo, R., Guler, R., Gusev, O., Gustincich, S., Ha, T. J., Haberle, V., Hale, P., Hallstrom, B. M., Hamada, M., Handoko, L., Hara, M., Harbers, M., Harrow, J., Harshbarger, J., Hase, T., Hashimoto, K., Hatano, T., Hattori, N., Hayashi, R., Herlyn, M., Hettne, K., Heutink, P., Hide, W., Hitchens, K. J., Sui, S. H., 't Hoen, P. A. C., Hon, C. C., Hori, F., Horie, M., Horimoto, K., Horton, P., Hou, R., Huang, E., Huang, Y., Hugues, R., Hume, D., Ienasescu, H., Iida, K., Ikawa, T., Ikemura, T., Ikeo, K., Inoue, N., Ishizu, Y., Ito, Y., Ivshina, A. V., Jankovic, B. R., Jenjaroenpun, P., Johnson, R., Jorgensen, M., Jorjani, H., Joshi, A., Jurman, G., Kaczkowski, B., Kai, C., Kaida, K., Kajiyama, K., Kaliyaperumal, R., Kaminuma, E., Kanaya, T., Kaneda, H., Kapranov, P., Kasianov, A. S., Katayama, T., Kato, S., Kawaguchi, S., Kawai, J., Kawaji, H., Kawamoto, H., Kawamura, Y. I., Kawasaki, S., Kawashima, T., Kempfle, J. S., Kenna, T. J., Kere, J., Khachigian, L., Kiryu, H., Kishima, M., Kitajima, H., Kitamura, T., Kitano, H., Klaric, E., Klepper, K., Klinken, S. P., Kloppmann, E., Knox, A. J., Kodama, Y., Kogo, Y., Kojima, M., Kojima, S., Komatsu, N., Komiyama, H., Kono, T., Koseki, H., Koyasu, S., Kratz, A., Kukalev, A., Kulakovskiy, I., Kundaje, A., Kunikata, H., Kuo, R., Kuo, T., Kuraku, S., Kuznetsov, V. A., Kwon, T. J., Larouche, M., Lassmann, T., Law, A., Le-Cao, K. -A., Lecellier, C. -H., Lee, W., Lenhard, B., Lennartsson, A., Li, K., Li, R., Lilje, B., Lipovich, L., Lizio, M., Lopez, G., Magi, S., Mak, G. K., Makeev, V., Manabe, R., Mandai, M., Mar, J., Maruyama, K., Maruyama, T., Mason, E., Mathelier, A., Matsuda, H., Medvedeva, Y. A., Meehan, T. F., Mejhert, N., Meynert, A., Mikami, N., Minoda, A., Miura, H., Miyagi, Y., Miyawaki, A., Mizuno, Y., Morikawa, H., Morimoto, M., Morioka, M., Morishita, S., Moro, K., Motakis, E., Motohashi, H., Mukarram, A. K., Mummery, C. L., Mungall, C. J., Murakawa, Y., Muramatsu, M., Nagasaka, K., Nagase, T., Nakachi, Y., Nakahara, F., Nakai, K., Nakamura, K., Nakamura, Y., Nakazawa, T., Nason, G. P., Nepal, C., Nguyen, Q. H., Nielsen, L. K., Nishida, K., Nishiguchi, K. M., Nishiyori, H., Nitta, K., Notredame, C., Ogishima, S., Ohkura, N., Ohno, H., Ohshima, M., Ohtsu, T., Okada, Y., Okada-Hatakeyama, M., Okazaki, Y., Oksvold, P., Orlando, V., Ow, G. S., Ozturk, M., Pachkov, M., Paparountas, T., Parihar, S. P., Park, S. -J., Pascarella, G., Passier, R., Persson, H., Philippens, I. H., Piazza, S., Plessy, C., Pombo, A., Ponten, F., Poulain, S., Poulsen, T. M., Pradhan, S., Prezioso, C., Pridans, C., Qin, X. -Y., Quackenbush, J., Rackham, O., Ramilowski, J., Ravasi, T., Rehli, M., Rennie, S., Rito, T., Rizzu, P., Robert, C., Roos, M., Rost, B., Roudnicky, F., Roy, R., Rye, M. B., Sachenkova, O., Saetrom, P., Sai, H., Saiki, S., Saito, M., Saito, A., Sakaguchi, S., Sakai, M., Sakaue, S., Sakaue-Sawano, A., Sandelin, A., Sano, H., Sasamoto, Y., Sato, H., Saxena, A., Saya, H., Schafferhans, A., Schmeier, S., Schmidl, C., Schmocker, D., Schneider, C., Schueler, M., Schultes, E. A., Schulze-Tanzil, G., Semple, C. A., Seno, S., Seo, W., Sese, J., Sheng, G., Shi, J., Shimoni, Y., Shin, J. W., Simonsanchez, J., Sivertsson, A., Sjostedt, E., Soderhall, C., Laurent, G. S., Stoiber, M. H., Sugiyama, D., Summers, K. M., Suzuki, A. M., Suzuki, K., Suzuki, M., Suzuki, N., Suzuki, T., Swanson, D. J., Swoboda, R. K., Taguchi, A., Takahashi, H., Takahashi, M., Takamochi, K., Takeda, S., Takenaka, Y., Tam, K. T., Tanaka, H., Tanaka, R., Tanaka, Y., Tang, D., Taniuchi, I., Tanzer, A., Tarui, H., Taylor, M. S., Terada, A., Terao, Y., Testa, A. C., Thomas, M., Thongjuea, S., Tomii, K., Triglia, E. T., Toyoda, H., Tsang, H. G., Tsujikawa, M., Uhlen, M., Valen, E., van de Wetering, M., van Nimwegen, E., Velmeshev, D., Verardo, R., Vitezic, M., Vitting-Seerup, K., von Feilitzen, K., Voolstra, C. R., Vorontsov, I. E., Wahlestedt, C., Wasserman, W. W., Watanabe, K., Watanabe, S., Wells, C. A., Winteringham, L. N., Wolvetang, E., Yabukami, H., Yagi, K., Yamada, T., Yamaguchi, Y., Yamamoto, M., Yamamoto, Y., Yamanaka, Y., Yano, K., Yasuzawa, K., Yatsuka, Y., Yo, M., Yokokura, S., Yoneda, M., Yoshida, E., Yoshida, Y., Yoshihara, M., Young, R., Young, R. S., Yu, N. Y., Yumoto, N., Zabierowski, S. E., Zhang, P. G., Zucchelli, S., Zwahlen, M., Chatelain, C., Brehelin, L., Institute of Biotechnology, Biosciences, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Computationnelle (IBC), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), National Institute of Advanced Industrial Science and Technology (AIST), SANOFI Recherche, University of British Columbia (UBC), Experimental Immunology, Infectious diseases, AII - Infectious diseases, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)

Subjects
0301 basic medicine, General Physics and Astronomy, Genome, Mice, 0302 clinical medicine, Transcription (biology), Promoter Regions, Genetic, Transcription Initiation, Genetic, 0303 health sciences, Multidisciplinary, 1184 Genetics, developmental biology, physiology, High-Throughput Nucleotide Sequencing, Neurodegenerative Diseases, 222 Other engineering and technologies, Genomics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], humanities, Enhancer Elements, Genetic, Microsatellite Repeat, Transcription Initiation Site, Sequence motif, Transcription Initiation, Human, Enhancer Elements, Neural Networks, Science, 610 Medicine & health, Computational biology, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Promoter Regions, 03 medical and health sciences, Computer, Deep Learning, Tandem repeat, Genetic, Clinical Research, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Machine learning, Genetics, Animals, Humans, Polymorphism, Enhancer, Transcriptomics, Gene, A549 Cell, 030304 developmental biology, Polymorphism, Genetic, Neurodegenerative Disease, Base Sequence, Animal, Genome, Human, Human Genome, Computational Biology, Promoter, General Chemistry, 113 Computer and information sciences, Cap analysis gene expression, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cardiovascular and Metabolic Diseases, A549 Cells, Minion, Generic health relevance, 3111 Biomedicine, Neural Networks, Computer, 610 Medizin und Gesundheit, 030217 neurology & neurosurgery, FANTOM consortium, Microsatellite Repeats
Abstract

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism., Nature Communications, 12 (1), ISSN:2041-1723

Published
2020
Full Text
View/download PDF

2. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author

De Rie D., Abugessaisa I., Alam T., Arner E., Arner P., Ashoor H., Åström G., Babina M., Bertin N., Burroughs A., Carlisle A., Daub C., Detmar M., Deviatiiarov R., Fort A., Gebhard C., Goldowitz D., Guhl S., Ha T., Harshbarger J., Hasegawa A., Hashimoto K., Herlyn M., Heutink P., Hitchens K., Hon C., Huang E., Ishizu Y., Kai C., Kasukawa T., Klinken P., Lassmann T., Lecellier C., Lee W., Lizio M., Makeev V., Mathelier A., Medvedeva Y., Mejhert N., Mungall C., Noma S., Ohshima M., Okada-Hatakeyama M., Persson H., Rizzu P., Roudnicky F., Sætrom P., Sato H., Severin J., Shin J., Swoboda R., Tarui H., Toyoda H., Vitting-Seerup K., Winteringham L., Yamaguchi Y., Yasuzawa K., Yoneda M., Yumoto N., Zabierowski S., Zhang P., Wells C., Summers K., Kawaji H., Sandelin A., Rehli M., and Hayashizaki Y.

Abstract

© 2017 Nature America, Inc., part of Springer Nature. MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

Published
2017

3. The statistical geometry of transcriptome divergence in cell-type evolution and cancer

Author

Liang, C, Alam, I, Albanese, D, Altschuler, G, Andersson, R, Arakawa, T, Archer, J, Arner, E, Arner, P, Babina, M, Baillie, K, Bajic, V, Baker, S, Balic, A, Balwierz, P, Beckhouse, A, Bertin, N, Blake, Ja, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Burroughs, M, Califano, A, Cannistraci, C, Carbajo, D, Carninci, P, Chen, Yang, Chierici, M, Ciani, Y, Clevers, H, Dalla, Emiliano, Daub, C, Davis, C, De Hoon, M, De Lima Morais, D, Dermar, M, Diehl, A, Dimont, E, Dohl, T, Drabros, F, Edge, A, Edinger, M, Ekwall, K, Endoh, M, Enomoto, H, Fagiolini, M, Fairbairn, L, Fang, H, Farach Carson, Mc, Faulkner, G, Favorov, A, Fisher, M, Forrest, A, Francescatto, M, Freeman, T, Frith, M, Fujita, R, Fukuda, S, Furlanello, C, Furuno, M, Furusawa, J, Geijtenbeek, Tb, Gibson, A, Gingeras, T, Goldowithz, D, Gough, J, Guhl, S, Guler, R, Gustincich, Stefano, Ha, T, Haberle, V, Hamaguchi, M, Hara, M, Harbers, M, Harshbarger, J, Hasegawa, A, Hasegawa, Y, Hashimoto, T, Hayashizaki, Y, Herlyn, M, Heutink, P, Hide, W, Hitchens, K, Ho Sui, S, Hofmann, O, Hoof, I, Hori, F, Hume, D, Huminiecki, L, Iida, K, Ikawa, T, Ishizu, Y, Itoh, M, Jankovic, B, Jia, H, Jorgensen, M, Joshi, A, Jurman, G, Kaczkowski, B, Kai, C, Kaida, K, Kaiho, A, Kajiyama, K, Kanamori Katayama, M, Kasianov, A, Kasukawa, T, Katayama, S, Kato Ishikawa, S, Kawaguchi, S, Kawai, J, Kawaji, H, Kawamoto, H, Kawamura, Y, Kawashima, T, Kempfle, J, Kenna, T, Kere, J, Khachigian, L, Kitamura, T, Klinken, P, Knox, A, Kojima, M, Kojima, S, Kondo, N, Koseki, H, Koyasu, S, Krampitz, S, Kubosaki, A, Kulakovskiy, I, Kwon, At, Laros, J, Lassmann, T, Lenhard, B, Lennartsson, A, Li, K, Lilji, B, Lipovich, L, Lizio, M, Mackay Sim, A, Makeev, V, Manabe, R, Mar, J, Marchand, B, Mathelier, A, Medvedeva, Y, Meehan, Tf, Mejhert, N, Meynert, A, Mizuno, Y, Morikawa, H, Morimoto, M, Moro, K, Motakis, E, Motohashi, H, Mummery, C, Mungall, Cj, Murata, M, Nagao Sato, S, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nakazato, K, Ninomiya Fukuda, N, Nishiyori Sueki, H, Noma, S, Nozaki, T, Ogishima, S, Ohkura, N, Ohmiya, H, Ohno, H, Ohshima, M, Okada Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, D, Pain, A, Passier, R, Persson, H, Piazza, Silvano, Plessy, C, Pradhan Bhatt, S, Prendergast, J, Rackham, O, Ramilowski, J, Rashid, M, Ravasi, T, Rehli, M, Rizzu, P, Roncador, M, Roy, S, Rye, M, Saijyo, E, Sajantila, A, Saka, A, Sakaguchi, S, Sakai, M, Sandelin, A, Sato, H, Satoh, H, Suzana, S, Alka, S, Schaefer, U, Schmeier, S, Schmidl, C, Schneider, C, Schultes, Ea, Schulze Tanzil, G, Schwegmann, A, Semple, C, Sengstag, T, Severin, J, Sheng, G, Shimoji, H, Shimoni, Y, Shin, J, Simon, C, Sugiyama, D, Sugiyama, T, Summers, K, Suzuki, H, Suzuki, M, Suzuki, N, Swoboda, R, Hoen P, T, Tagami, M, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tatum, Z, Taylor, M, Thompson, M, Toyoda, H, Toyoda, T, Valen, E, Van De Wetering, M, Van Den Berg, L, Van Nimwegen, E, Verardo, R, Vijayan, D, Vitezic, M, Vorontzov, I, Wasserman, W, Watanabe, S, Wells, C, Winteringham, L, Wolvetang, E, Wood, Ej, Yamaguchi, Y, Yamamoto, M, Yoneda, M, Yonekura, Y, Yoshida, Shin'Ichirou, Young, R, Zabierowski, Se, Zhang, P, Zhao, X, Zucchelli, Silvia, Forrest, Ar, Wagner, Gp, Hubrecht Institute for Developmental Biology and Stem Cell Research, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, and Experimental Immunology

Subjects
Cell type, General Physics and Astronomy, rna-seq data, phylogenetic networks, Biology, ENCODE, General Biochemistry, Genetics and Molecular Biology, Divergence, Transcriptome, Models, Settore BIO/13 - Biologia Applicata, Neoplasms, Humans, Genetics, Models, Statistical, Multidisciplinary, Statistical model, General Chemistry, Statistical, Biological Evolution, Body plan, Tree structure, Evolutionary biology, Cancer cell
Abstract

In evolution, body plan complexity increases due to an increase in the number of individualized cell types. Yet, there is very little understanding of the mechanisms that produce this form of organismal complexity. One model for the origin of novel cell types is the sister cell-type model. According to this model, each cell type arises together with a sister cell type through specialization from an ancestral cell type. A key prediction of the sister cell-type model is that gene expression profiles of cell types exhibit tree structure. Here we present a statistical model for detecting tree structure in transcriptomic data and apply it to transcriptomes from ENCODE and FANTOM5. We show that transcriptomes of normal cells harbour substantial amounts of hierarchical structure. In contrast, cancer cell lines have less tree structure, suggesting that the emergence of cancer cells follows different principles from that of evolutionary cell-type origination.

Published
2015
Full Text
View/download PDF

4. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author

De Rie D., Abugessaisa I., Alam T., Arner E., Arner P., Ashoor H., Åström G., Babina M., Bertin N., Burroughs A., Carlisle A., Daub C., Detmar M., Deviatiiarov R., Fort A., Gebhard C., Goldowitz D., Guhl S., Ha T., Harshbarger J., Hasegawa A., Hashimoto K., Herlyn M., Heutink P., Hitchens K., Hon C., Huang E., Ishizu Y., Kai C., Kasukawa T., Klinken P., Lassmann T., Lecellier C., Lee W., Lizio M., Makeev V., Mathelier A., Medvedeva Y., Mejhert N., Mungall C., Noma S., Ohshima M., Okada-Hatakeyama M., Persson H., Rizzu P., Roudnicky F., Sætrom P., Sato H., Severin J., Shin J., Swoboda R., Tarui H., Toyoda H., Vitting-Seerup K., Winteringham L., Yamaguchi Y., Yasuzawa K., Yoneda M., Yumoto N., Zabierowski S., Zhang P., Wells C., Summers K., Kawaji H., Sandelin A., Rehli M., Hayashizaki Y., De Rie D., Abugessaisa I., Alam T., Arner E., Arner P., Ashoor H., Åström G., Babina M., Bertin N., Burroughs A., Carlisle A., Daub C., Detmar M., Deviatiiarov R., Fort A., Gebhard C., Goldowitz D., Guhl S., Ha T., Harshbarger J., Hasegawa A., Hashimoto K., Herlyn M., Heutink P., Hitchens K., Hon C., Huang E., Ishizu Y., Kai C., Kasukawa T., Klinken P., Lassmann T., Lecellier C., Lee W., Lizio M., Makeev V., Mathelier A., Medvedeva Y., Mejhert N., Mungall C., Noma S., Ohshima M., Okada-Hatakeyama M., Persson H., Rizzu P., Roudnicky F., Sætrom P., Sato H., Severin J., Shin J., Swoboda R., Tarui H., Toyoda H., Vitting-Seerup K., Winteringham L., Yamaguchi Y., Yasuzawa K., Yoneda M., Yumoto N., Zabierowski S., Zhang P., Wells C., Summers K., Kawaji H., Sandelin A., Rehli M., and Hayashizaki Y.

Abstract

© 2017 Nature America, Inc., part of Springer Nature. MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

5. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author

De Rie D., Abugessaisa I., Alam T., Arner E., Arner P., Ashoor H., Åström G., Babina M., Bertin N., Burroughs A., Carlisle A., Daub C., Detmar M., Deviatiiarov R., Fort A., Gebhard C., Goldowitz D., Guhl S., Ha T., Harshbarger J., Hasegawa A., Hashimoto K., Herlyn M., Heutink P., Hitchens K., Hon C., Huang E., Ishizu Y., Kai C., Kasukawa T., Klinken P., Lassmann T., Lecellier C., Lee W., Lizio M., Makeev V., Mathelier A., Medvedeva Y., Mejhert N., Mungall C., Noma S., Ohshima M., Okada-Hatakeyama M., Persson H., Rizzu P., Roudnicky F., Sætrom P., Sato H., Severin J., Shin J., Swoboda R., Tarui H., Toyoda H., Vitting-Seerup K., Winteringham L., Yamaguchi Y., Yasuzawa K., Yoneda M., Yumoto N., Zabierowski S., Zhang P., Wells C., Summers K., Kawaji H., Sandelin A., Rehli M., Hayashizaki Y., De Rie D., Abugessaisa I., Alam T., Arner E., Arner P., Ashoor H., Åström G., Babina M., Bertin N., Burroughs A., Carlisle A., Daub C., Detmar M., Deviatiiarov R., Fort A., Gebhard C., Goldowitz D., Guhl S., Ha T., Harshbarger J., Hasegawa A., Hashimoto K., Herlyn M., Heutink P., Hitchens K., Hon C., Huang E., Ishizu Y., Kai C., Kasukawa T., Klinken P., Lassmann T., Lecellier C., Lee W., Lizio M., Makeev V., Mathelier A., Medvedeva Y., Mejhert N., Mungall C., Noma S., Ohshima M., Okada-Hatakeyama M., Persson H., Rizzu P., Roudnicky F., Sætrom P., Sato H., Severin J., Shin J., Swoboda R., Tarui H., Toyoda H., Vitting-Seerup K., Winteringham L., Yamaguchi Y., Yasuzawa K., Yoneda M., Yumoto N., Zabierowski S., Zhang P., Wells C., Summers K., Kawaji H., Sandelin A., Rehli M., and Hayashizaki Y.

Abstract

© 2017 Nature America, Inc., part of Springer Nature. MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

6. Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor.

Author

He B, Dymond L, Wood KH, Bastow ER, Satiaputra J, Li J, Johansson-Percival A, Hamzah J, Kumarasinghe MP, Ballal M, Foo J, Johansson M, Ee HC, White SW, Winteringham L, and Ganss R

Subjects
Animals, Humans, Mice, Disease Models, Animal, Tumor Necrosis Factor Ligand Superfamily Member 14 metabolism, Tumor Necrosis Factor Ligand Superfamily Member 14 genetics, Fetal Blood cytology, Tumor Microenvironment immunology, Xenograft Model Antitumor Assays, Immunotherapy methods, Neovascularization, Pathologic immunology, Neovascularization, Pathologic pathology, Cell Line, Tumor, Gastrointestinal Neoplasms immunology, Gastrointestinal Neoplasms pathology, Gastrointestinal Neoplasms therapy, Gastrointestinal Stromal Tumors immunology, Gastrointestinal Stromal Tumors pathology, Gastrointestinal Stromal Tumors therapy, Tertiary Lymphoid Structures immunology, Tertiary Lymphoid Structures pathology
Abstract

Gastrointestinal stromal tumors (GISTs) harbor diverse immune cell populations but so far immunotherapy in patients has been disappointing. Here, we established cord blood humanized mouse models of localized and disseminated GIST to explore the remodeling of the tumor environment for improved immunotherapy. Specifically, we assessed the ability of a cancer vascular targeting peptide (VTP) to bind to mouse and patient GIST angiogenic blood vessels and deliver the TNF superfamily member LIGHT (TNFS14) into tumors. LIGHT-VTP treatment of GIST in humanized mice improved vascular function and tumor oxygenation, which correlated with an overall increase in intratumoral human effector T cells. Concomitant with LIGHT-mediated vascular remodeling, we observed intratumoral high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), which resemble spontaneous TLS found in GIST patients. Thus, by overcoming the limitations of immunodeficient xenograft models, we demonstrate the therapeutic feasibility of vascular targeting and immune priming in human GIST. Since TLS positively correlate with patient prognosis and improved response to immune checkpoint inhibition, vascular LIGHT targeting in GIST is a highly translatable approach to improve immunotherapeutic outcomes., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Published
2024
Full Text
View/download PDF

7. ECM Depletion Is Required to Improve the Intratumoral Uptake of Iron Oxide Nanoparticles in Poorly Perfused Hepatocellular Carcinoma.

Author

Yeow YL, Wu J, Wang X, Winteringham L, Feindel KW, Tirnitz-Parker JEE, Leedman PJ, Ganss R, and Hamzah J

Abstract

Improving tumor access for drug delivery is challenging, particularly in poorly perfused tumors. The availability of functional tumor blood vessels for systemic access is vital to allow drugs or imaging agents to accumulate in the tumor parenchyma. We subjected mice engineered to develop hepatocellular carcinoma (HCC), to treatment with tumor necrosis factor alpha (TNFα) conjugated to a CSG peptide (CSGRRSSKC). CSG binds to the laminin-nidogen-1 complex of the extracellular matrix (ECM) in HCC. When produced as a recombinant fusion protein, the TNFα-CSG functions as an ECM depletion agent via an immune-mediated mechanism to improve tumor perfusion. Tumor perfusion in HCC was dramatically improved after daily intravenous (i.v.) injection of 5 µg TNFα-CSG for five consecutive days. Following treatment, we assessed the tumor accessibility to accumulate an imaging agent, superparamagnetic iron-oxide nanoparticles (IO-NP). Here, we compared the passive delivery of an i.v. dose of IO-NP in HCC following ECM depletion after TNFα-CSG treatment, to the intratumoral accumulation of a comparable dose of CSG-targeted IO-NP in HCC with intact ECM. Magnetic resonance imaging (MRI) T 2 -weighted scans and T 2 relaxation times indicate that when the tumor ECM is intact, HCC was resistant to the intratumoral uptake of IO-NP, even when the particles were tagged with CSG peptide. In contrast, pre-treatment with TNFα-CSG resulted in the highest IO-NP accumulation in tumors. These findings suggest poorly perfused HCC may be resistant to molecular-targeted imaging agents including CSG-IO-NP. We demonstrate that specific ECM depletion using TNFα-CSG improves nanoparticle delivery into poorly perfused tumors such as HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yeow, Wu, Wang, Winteringham, Feindel, Tirnitz-Parker, Leedman, Ganss and Hamzah.)

Published
2022
Full Text
View/download PDF

8. Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix.

Author

Chopra M, Wu J, Yeow YL, Winteringham L, Clemons TD, Saunders M, Kotamraju VR, Ganss R, Feindel KW, and Hamzah J

Abstract

Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET). In contrast, a control untargeted IO-NP consistently show poor tumour uptake, and IO-NP conjugated to a pentapeptide. CREKA that bind fibrin clots in blood vessels show restricted uptake in the angiogenic vessels of the tumours. CSG-IO-NP show three-fold higher intratumoral accumulation compared to CREKA-IO-NP. Magnetic resonance imaging (MRI) T 2 -weighted scans and T 2 relaxation times indicate significant uptake of CSG-IO-NP irrespective of tumour size, whereas the uptake of CREKA-IO-NP is only consistent in small tumours of less than 3 mm in diameter. Larger tumours with significantly reduced tumour blood vessels show a lack of CREKA-IO-NP uptake. Our data suggest CSG-IO-NP are particularly useful for detecting stroma in early and advanced solid tumours.

Published
2021
Full Text
View/download PDF

9. An integrated expression atlas of miRNAs and their promoters in human and mouse.

Author

de Rie D, Abugessaisa I, Alam T, Arner E, Arner P, Ashoor H, Åström G, Babina M, Bertin N, Burroughs AM, Carlisle AJ, Daub CO, Detmar M, Deviatiiarov R, Fort A, Gebhard C, Goldowitz D, Guhl S, Ha TJ, Harshbarger J, Hasegawa A, Hashimoto K, Herlyn M, Heutink P, Hitchens KJ, Hon CC, Huang E, Ishizu Y, Kai C, Kasukawa T, Klinken P, Lassmann T, Lecellier CH, Lee W, Lizio M, Makeev V, Mathelier A, Medvedeva YA, Mejhert N, Mungall CJ, Noma S, Ohshima M, Okada-Hatakeyama M, Persson H, Rizzu P, Roudnicky F, Sætrom P, Sato H, Severin J, Shin JW, Swoboda RK, Tarui H, Toyoda H, Vitting-Seerup K, Winteringham L, Yamaguchi Y, Yasuzawa K, Yoneda M, Yumoto N, Zabierowski S, Zhang PG, Wells CA, Summers KM, Kawaji H, Sandelin A, Rehli M, Hayashizaki Y, Carninci P, Forrest ARR, and de Hoon MJL

Subjects
Animals, Cells, Cultured, Gene Library, High-Throughput Nucleotide Sequencing, Humans, Mice, MicroRNAs metabolism, Gene Expression Profiling methods, MicroRNAs genetics, Molecular Sequence Annotation, Promoter Regions, Genetic genetics
Abstract

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.

Published
2017
Full Text
View/download PDF

10. Hls5 regulated erythroid differentiation by modulating GATA-1 activity.

Author

Endersby R, Majewski IJ, Winteringham L, Beaumont JG, Samuels A, Scaife R, Lim E, Crossley M, Klinken SP, and Lalonde JP

Subjects
Cell Cycle, Cell Differentiation drug effects, Cell Line, Cell Line, Tumor, DNA Primers, Erythropoietin pharmacology, Globins genetics, Humans, Leukemia, Erythroblastic, Acute, Nuclear Proteins physiology, Transcription Factors physiology, Apoptosis Regulatory Proteins physiology, Cell Differentiation physiology, GATA1 Transcription Factor physiology
Abstract

Hemopoietic lineage switch (Hls) 5 and 7 were originally isolated as genes up-regulated during an erythroid-to-myeloid lineage switch. We have shown previously that Hls7/Mlf1 imposes a monoblastoid phenotype on erythroleukemic cells. Here we show that Hls5 impedes erythroid maturation by restricting proliferation and inhibiting hemoglobin synthesis; however, Hls5 does not influence the morphology of erythroid cells. Under the influence of GATA-1, Hls5 relocates from cytoplasmic granules to the nucleus where it associates with both FOG-1 and GATA-1. In the nucleus, Hls5 is able to suppress GATA-1-mediated transactivation and reduce GATA-1 binding to DNA. We conclude that Hls5 and Hls7/Mlf1 act cooperatively to induce biochemical and phenotypic changes associated with erythroid/myeloid lineage switching.

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results