Impact of regulatory variation across human iPSCs and differentiated cells
作者： Nicholas E. Banovich , Yang I. Li , Anil Raj , Michelle C. Ward , Peyton Greenside
关键词: Chromatin 、 Biology 、 Computational biology 、 Regulation of gene expression 、 Cellular differentiation 、 Genetic variation 、 Quantitative trait locus 、 Induced pluripotent stem cell 、 DNA methylation 、 Cell type
摘要: Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that otherwise difficult to access. We investigated the use of iPSCs iPSC-derived study impact genetic variation on gene regulation across different as models studies complex disease. To do so, we established a panel from 58 well-studied Yoruba lymphoblastoid lines (LCLs); 14 these were further differentiated into cardiomyocytes. characterized regulatory individuals by measuring expression levels, chromatin accessibility, DNA methylation. Our analysis focused comparison inter-individual types. While most cell-type-specific quantitative trait loci (QTLs) lie in is open only affected types, found 20% QTLs shared chromatin. This observation motivated us develop deep neural network predict regions sequence alone. Using this approach, able sequences segregating haplotypes effects common SNPs accessibility.
sci-hub.se 参考文章(63)
Matthew D. Zeiler, ADADELTA: An Adaptive Learning Rate Method arXiv: Learning. ,(2012)
Maxwell W. Libbrecht, William Stafford Noble, Machine learning applications in genetics and genomics Nature Reviews Genetics. ,vol. 16, pp. 321- 332 ,(2015) , 10.1038/NRG3920
GTEx Consortium, Kristin G Ardlie, David S Deluca, Ayellet V Segrè, Timothy J Sullivan, Taylor R Young, Ellen T Gelfand, Casandra A Trowbridge, Julian B Maller, Taru Tukiainen, Monkol Lek, Lucas D Ward, Pouya Kheradpour, Benjamin Iriarte, Yan Meng, Cameron D Palmer, Tõnu Esko, Wendy Winckler, Joel N Hirschhorn, Manolis Kellis, Daniel G MacArthur, Gad Getz, Andrey A Shabalin, Gen Li, Yi-Hui Zhou, Andrew B Nobel, Ivan Rusyn, Fred A Wright, Tuuli Lappalainen, Pedro G Ferreira, Halit Ongen, Manuel A Rivas, Alexis Battle, Sara Mostafavi, Jean Monlong, Michael Sammeth, Marta Mele, Ferran Reverter, Jakob M Goldmann, Daphne Koller, Roderic Guigó, Mark I McCarthy, Emmanouil T Dermitzakis, Eric R Gamazon, Hae Kyung Im, Anuar Konkashbaev, Dan L Nicolae, Nancy J Cox, Timothée Flutre, Xiaoquan Wen, Matthew Stephens, Jonathan K Pritchard, Zhidong Tu, Bin Zhang, Tao Huang, Quan Long, Luan Lin, Jialiang Yang, Jun Zhu, Jun Liu, Amanda Brown, Bernadette Mestichelli, Denee Tidwell, Edmund Lo, Mike Salvatore, Saboor Shad, Jeffrey A Thomas, John T Lonsdale, Michael T Moser, Bryan M Gillard, Ellen Karasik, Kimberly Ramsey, Christopher Choi, Barbara A Foster, John Syron, Johnell Fleming, Harold Magazine, Rick Hasz, Gary D Walters, Jason P Bridge, Mark Miklos, Susan Sullivan, Laura K Barker, Heather M Traino, Maghboeba Mosavel, Laura A Siminoff, Dana R Valley, Daniel C Rohrer, Scott D Jewell, Philip A Branton, Leslie H Sobin, Mary Barcus, Liqun Qi, Jeffrey McLean, Pushpa Hariharan, Ki Sung Um, Shenpei Wu, David Tabor, Charles Shive, Anna M Smith, Stephen A Buia, Anita H Undale, Karna L Robinson, Nancy Roche, Kimberly M Valentino, Angela Britton, Robin Burges, Debra Bradbury, Kenneth W Hambright, John Seleski, Greg E Korzeniewski, Kenyon Erickson, Yvonne Marcus, Jorge Tejada, Mehran Taherian, Chunrong Lu, Margaret Basile, Deborah C Mash, Simona Volpi, Jeffery P Struewing, Gary F Temple, Joy Boyer, Deborah Colantuoni, Roger Little, Susan Koester, Latarsha J Carithers, Helen M Moore, Ping Guan, Carolyn Compton, Sherilyn J Sawyer, Joanne P Demchok, Jimmie B Vaught, Chana A Rabiner, Nicole C Lockhart, Kristin G Ardlie, Gad Getz, Fred A Wright, Manolis Kellis, Simona Volpi, Emmanouil T Dermitzakis, None, The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans Science. ,vol. 348, pp. 648- 660 ,(2015) , 10.1126/SCIENCE.1262110
Leonardo D’Aiuto, Yun Zhi, Dhanjit Kumar Das, Madeleine R Wilcox, Jon W Johnson, Lora McClain, Matthew L MacDonald, Roberto Di Maio, Mark E Schurdak, Paolo Piazza, Luigi Viggiano, Robert Sweet, Paul R Kinchington, Ayantika G Bhattacharjee, Robert Yolken, Vishwajit L Nimgaonka, Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation Organogenesis. ,vol. 10, pp. 365- 377 ,(2014) , 10.1080/15476278.2015.1011921
Hilary K Finucane, Brendan Bulik-Sullivan, Alexander Gusev, Gosia Trynka, Yakir Reshef, Po-Ru Loh, Verneri Anttila, Han Xu, Chongzhi Zang, Kyle Farh, Stephan Ripke, Felix R Day, ReproGen Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Raci Consortium, Shaun Purcell, Eli Stahl, Sara Lindstrom, John RB Perry, Yukinori Okada, Soumya Raychaudhuri, Mark J Daly, Nick Patterson, Benjamin M Neale, Alkes L Price, None, Partitioning heritability by functional annotation using genome-wide association summary statistics Nature Genetics. ,vol. 47, pp. 1228- 1235 ,(2015) , 10.1038/NG.3404
J. D. Storey, R. Tibshirani, Statistical significance for genomewide studies Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 9440- 9445 ,(2003) , 10.1073/PNAS.1530509100
Franz-Josef Müller, Bernhard M Schuldt, Roy Williams, Dylan Mason, Gulsah Altun, Eirini P Papapetrou, Sandra Danner, Johanna E Goldmann, Arne Herbst, Nils O Schmidt, Josef B Aldenhoff, Louise C Laurent, Jeanne F Loring, A bioinformatic assay for pluripotency in human cells Nature Methods. ,vol. 8, pp. 315- 317 ,(2011) , 10.1038/NMETH.1580
Ping Liang, Feng Lan, Andrew S. Lee, Tingyu Gong, Veronica Sanchez-Freire, Yongming Wang, Sebastian Diecke, Karim Sallam, Joshua W. Knowles, Paul J. Wang, Patricia K. Nguyen, Donald M. Bers, Robert C. Robbins, Joseph C. Wu, Drug Screening Using a Library of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes Reveals Disease-Specific Patterns of Cardiotoxicity Circulation. ,vol. 127, pp. 1677- 1691 ,(2013) , 10.1161/CIRCULATIONAHA.113.001883
C. H. WADDINGTON, Canalization of Development and Genetic Assimilation of Acquired Characters Nature. ,vol. 183, pp. 1654- 1655 ,(1959) , 10.1038/1831654A0
Foad Rouhani, Natsuhiko Kumasaka, Miguel Cardoso de Brito, Allan Bradley, Ludovic Vallier, Daniel Gaffney, Genetic Background Drives Transcriptional Variation in Human Induced Pluripotent Stem Cells PLoS Genetics. ,vol. 10, pp. e1004432- ,(2014) , 10.1371/JOURNAL.PGEN.1004432