Deciphering regulation in eukaryotic cell: from sequence to function
作者： Valentina Boeva
DOI:
关键词: Genome 、 Transcription factor 、 Chromothripsis 、 Biology 、 Genetics 、 Sequence analysis 、 Transcriptional regulation 、 Reference genome 、 Gene 、 DNA binding site 、 Computational biology
摘要: A transversal topic of my research has been the development and application computational methods for DNA sequence analysis. The I have developing aim at improving our understanding regulation processes happening in normal cancer cells. This connects together projects presented this thesis. Two chapters thesis represent major areas interests: (1) deciphering transcriptional their to answer specific biological questions, (2) study genome structure studies. first chapter predominantly focuses on regulation. Here describe contribution methodology discovery transcription factor binding sites positioning histone proteins. also explain how analysis, combination with gene expression data, can allow identification direct target genes a under study, as well physical mechanisms its action. As two examples, provide results by (i) oncogenic protein EWS-FLI1 Ewing sarcoma (ii) Spi-1/PU.1 erythroleukemia. In second chapter, analysis aimed genomic rearrangements species existing reference genome. developed be applied detect genomes. an example such tumor genomes result new phenomenon: chromothripsis, when hundreds occur single cellular catastrophe. is concluded listing challenges high-throughput sequencing discuss current top questions demanding integration data.
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Christian Korfhage, Evelyn Fisch, Evelyn Fricke, Silke Baedker, Dirk Loeffert, Whole‐Genome Amplification of Single‐Cell Genomes for Next‐Generation Sequencing Current protocols in molecular biology. ,vol. 104, ,(2013) , 10.1002/0471142727.MB0714S104
J. M. Leiden, Xiaohong Mao, C. B. Thompson, S. Miesfeldt, Haidi Yang, The FLI-1 and chimeric EWS-FLI-1 oncoproteins display similar DNA binding specificities. Journal of Biological Chemistry. ,vol. 269, pp. 18216- 18222 ,(1994) , 10.1016/S0021-9258(17)32437-7
Michael Brudno, Monica Stanciu, computational methods for discovering structural variation with next-generation ,(2009)
Robert J. Lonigro, Catherine S. Grasso, Dan R. Robinson, Xiaojun Jing, Yi-Mi Wu, Xuhong Cao, Michael J. Quist, Scott A. Tomlins, Kenneth J. Pienta, Arul M. Chinnaiyan, Detection of somatic copy number alterations in cancer using targeted exome capture sequencing. Neoplasia. ,vol. 13, pp. 1019- 1025 ,(2011) , 10.1593/NEO.111252
M B Small, N Hay, M Schwab, J M Bishop, Neoplastic transformation by the human gene N-myc. Molecular and Cellular Biology. ,vol. 7, pp. 1638- 1645 ,(1987) , 10.1128/MCB.7.5.1638
John M. Maris, Katherine K. Matthay, Molecular Biology of Neuroblastoma Journal of Clinical Oncology. ,vol. 17, pp. 2264- 2279 ,(1999) , 10.1200/JCO.1999.17.7.2264
Peggy J. Farnham, Insights from genomic profiling of transcription factors Nature Reviews Genetics. ,vol. 10, pp. 605- 616 ,(2009) , 10.1038/NRG2636
Matan Hofree, John P Shen, Hannah Carter, Andrew Gross, Trey Ideker, Network based stratification of tumor mutations Nature Methods. ,vol. 10, pp. 1108- 1115 ,(2015) , 10.1038/NMETH.2651
Peter V Kharchenko, Lev Silberstein, David T Scadden, Bayesian approach to single-cell differential expression analysis Nature Methods. ,vol. 11, pp. 740- 742 ,(2014) , 10.1038/NMETH.2967
Hongkai Ji, Hui Jiang, Wenxiu Ma, David S Johnson, Richard M Myers, Wing H Wong, An integrated software system for analyzing ChIP-chip and ChIP-seq data. Nature Biotechnology. ,vol. 26, pp. 1293- 1300 ,(2008) , 10.1038/NBT.1505