Deconvolving the contributions of cell-type heterogeneity on cortical gene expression

作者: Ellis Patrick , Mariko Taga , Ayla Ergun , Bernard Ng , William Casazza

DOI: 10.1371/JOURNAL.PCBI.1008120

关键词:

摘要: Complexity of cell-type composition has created much skepticism surrounding the interpretation bulk tissue transcriptomic studies. Recent studies have shown that deconvolution algorithms can be applied to computationally estimate proportions from gene expression data blood samples, but their performance when brain is unclear. Here, we generated an immunohistochemistry (IHC) dataset for five major cell-types 70 individuals, who also cortical data. With IHC as benchmark, this resource enables quantitative assessment tissue. We apply existing by using marker sets derived human single cell and cell-sorted RNA-seq show these indeed produce informative estimates constituent proportions. In fact, neuronal subpopulations estimated samples. Further, including proportion confounding factors important reducing false associations between Alzheimer's disease phenotypes expression. Lastly, demonstrate more accurate substantially improve statistical power in detecting specific trait loci (eQTLs).

参考文章(29)
Harm-Jan Westra, Danny Arends, Tõnu Esko, Marjolein J. Peters, Claudia Schurmann, Katharina Schramm, Johannes Kettunen, Hanieh Yaghootkar, Benjamin P. Fairfax, Anand Kumar Andiappan, Yang Li, Jingyuan Fu, Juha Karjalainen, Mathieu Platteel, Marijn Visschedijk, Rinse K. Weersma, Silva Kasela, Lili Milani, Liina Tserel, Pärt Peterson, Eva Reinmaa, Albert Hofman, André G. Uitterlinden, Fernando Rivadeneira, Georg Homuth, Astrid Petersmann, Roberto Lorbeer, Holger Prokisch, Thomas Meitinger, Christian Herder, Michael Roden, Harald Grallert, Samuli Ripatti, Markus Perola, Andrew R. Wood, David Melzer, Luigi Ferrucci, Andrew B. Singleton, Dena G. Hernandez, Julian C. Knight, Rossella Melchiotti, Bernett Lee, Michael Poidinger, Francesca Zolezzi, Anis Larbi, De Yun Wang, Leonard H. van den Berg, Jan H. Veldink, Olaf Rotzschke, Seiko Makino, Veikko Salomaa, Konstantin Strauch, Uwe Völker, Joyce B. J. van Meurs, Andres Metspalu, Cisca Wijmenga, Ritsert C. Jansen, Lude Franke, Cell Specific eQTL Analysis without Sorting Cells PLOS Genetics. ,vol. 11, pp. e1005223- ,(2015) , 10.1371/JOURNAL.PGEN.1005223
Spyros Darmanis, Steven A. Sloan, Ye Zhang, Martin Enge, Christine Caneda, Lawrence M. Shuer, Melanie G. Hayden Gephart, Ben A. Barres, Stephen R. Quake, A survey of human brain transcriptome diversity at the single cell level Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, pp. 7285- 7290 ,(2015) , 10.1073/PNAS.1507125112
Shai S Shen-Orr, Renaud Gaujoux, Computational deconvolution: extracting cell type-specific information from heterogeneous samples. Current Opinion in Immunology. ,vol. 25, pp. 571- 578 ,(2013) , 10.1016/J.COI.2013.09.015
A. J. L. Barton, R. C. A. Pearson, A. Najlerahim, P. J. Harrison, Pre- and postmortem influences on brain RNA. Journal of Neurochemistry. ,vol. 61, pp. 1- 11 ,(1993) , 10.1111/J.1471-4159.1993.TB03532.X
Aaron M Newman, Chih Long Liu, Michael R Green, Andrew J Gentles, Weiguo Feng, Yue Xu, Chuong D Hoang, Maximilian Diehn, Ash A Alizadeh, Robust enumeration of cell subsets from tissue expression profiles Nature Methods. ,vol. 12, pp. 453- 457 ,(2015) , 10.1038/NMETH.3337
Alexander R. Abbas, Kristen Wolslegel, Dhaya Seshasayee, Zora Modrusan, Hilary F. Clark, Deconvolution of Blood Microarray Data Identifies Cellular Activation Patterns in Systemic Lupus Erythematosus PLoS ONE. ,vol. 4, pp. e6098- ,(2009) , 10.1371/JOURNAL.PONE.0006098
Michael J Hawrylycz, Ed S Lein, Angela L Guillozet-Bongaarts, Elaine H Shen, Lydia Ng, Jeremy A Miller, Louie N Van De Lagemaat, Kimberly A Smith, Amanda Ebbert, Zackery L Riley, Chris Abajian, Christian F Beckmann, Amy Bernard, Darren Bertagnolli, Andrew F Boe, Preston M Cartagena, M Mallar Chakravarty, Mike Chapin, Jimmy Chong, Rachel A Dalley, Barry David Daly, Chinh Dang, Suvro Datta, Nick Dee, Tim A Dolbeare, Vance Faber, David Feng, David R Fowler, Jeff Goldy, Benjamin W Gregor, Zeb Haradon, David R Haynor, John G Hohmann, Steve Horvath, Robert E Howard, Andreas Jeromin, Jayson M Jochim, Marty Kinnunen, Christopher Lau, Evan T Lazarz, Changkyu Lee, Tracy A Lemon, Ling Li, Yang Li, John A Morris, Caroline C Overly, Patrick D Parker, Sheana E Parry, Melissa Reding, Joshua J Royall, Jay Schulkin, Pedro Adolfo Sequeira, Clifford R Slaughterbeck, Simon C Smith, Andy J Sodt, Susan M Sunkin, Beryl E Swanson, Marquis P Vawter, Derric Williams, Paul Wohnoutka, H Ronald Zielke, Daniel H Geschwind, Patrick R Hof, Stephen M Smith, Christof Koch, Seth GN Grant, Allan R Jones, None, An anatomically comprehensive atlas of the adult human brain transcriptome Nature. ,vol. 489, pp. 391- 399 ,(2012) , 10.1038/NATURE11405
Yi Zhong, Ying-Wooi Wan, Kaifang Pang, Lionel ML Chow, Zhandong Liu, Digital sorting of complex tissues for cell type-specific gene expression profiles BMC Bioinformatics. ,vol. 14, pp. 89- 89 ,(2013) , 10.1186/1471-2105-14-89
Jerome Friedman, Trevor Hastie, Robert Tibshirani, Regularization Paths for Generalized Linear Models via Coordinate Descent Journal of Statistical Software. ,vol. 33, pp. 1- 22 ,(2010) , 10.18637/JSS.V033.I01
Dena Marrinucci, Kelly Bethel, Anand Kolatkar, Madelyn S Luttgen, Michael Malchiodi, Franziska Baehring, Katharina Voigt, Daniel Lazar, Jorge Nieva, Lyudmila Bazhenova, Andrew H Ko, W Michael Korn, Ethan Schram, Michael Coward, Xing Yang, Thomas Metzner, Rachelle Lamy, Meghana Honnatti, Craig Yoshioka, Joshua Kunken, Yelena Petrova, Devin Sok, David Nelson, Peter Kuhn, Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers Physical Biology. ,vol. 9, pp. 016003- 016003 ,(2012) , 10.1088/1478-3975/9/1/016003