CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell types.
We present a sensitive approach to predict genes expressed selectively in specific cell types, by searching publicly available expression data for genes with a similar expression profile to known cell-specific markers. Our method, CellMapper, strongly outperforms previous computational algorithms to predict cell type-specific expression, especially for rare and difficult-to-isolate cell types. Furthermore, CellMapper makes accurate predictions for human brain cell types that have never been isolated, and can be rapidly applied to diverse cell types from many tissues. We demonstrate a clinically relevant application to prioritize candidate genes in disease susceptibility loci identified by GWAS.
Division of Gastroenterology, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. bnelms.research@gmail.com.|Graduate Program in Biophysics, Harvard University, Cambridge, MA, 02138, USA. bnelms.research@gmail.com.
Bradlee D
BD
Nelms
City University of New York School of Public Health, New York, NY, 10027, USA.
Levi
L
Waldron
Graduate Program in Biophysics, Harvard University, Cambridge, MA, 02138, USA.|Division of Genetics, Department of Medicine and Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Luis A
LA
Barrera
Division of Gastroenterology, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Andrew W
AW
Weflen
Division of Gastroenterology, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Jeremy A
JA
Goettel
Center of Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Zhejiang, 310058, People's Republic of China.
Guoji
G
Guo
Division of Gastroenterology, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Robert K
RK
Montgomery
Division of Gastroenterology, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.|Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA, 02115, USA.
Marian R
MR
Neutra
Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA, 02115, USA.|Division of Endocrinology, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
David T
DT
Breault
Division of Gastroenterology, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.|Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA, 02115, USA.|Department of Gastroenterology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Scott B
SB
Snapper
Division of Hematology/Oncology and Harvard Stem Cell Institute, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.|Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Stuart H
SH
Orkin
Division of Genetics, Department of Medicine and Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Martha L
ML
Bulyk
Department of Biostatistics, Harvard School of Public Health, Boston, MA, 02115, USA.
Curtis
C
Huttenhower
Division of Gastroenterology, Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. wayne.lencer@childrens.harvard.edu.|Graduate Program in Biophysics, Harvard University, Cambridge, MA, 02138, USA. wayne.lencer@childrens.harvard.edu.|Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA, 02115, USA. wayne.lencer@childrens.harvard.edu.
Wayne I
WI
Lencer
D000465:Algorithms; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D018938:Caco-2 Cells; D002460:Cell Line; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D013154:Spleen / Q000166:cytology / Q000378:metabolism
Cell type; Expression; Genome-wide association study; Inflammatory bowel disease; Microarray
Genome Biol. 2010;11(12):R124
21182765
Genome Res. 2003 Aug;13(8):1828-37
12902378
Genome Res. 2003 Aug;13(8):1838-54
12869577
Nature. 2011 Jun 15;474(7351):307-17
21677747
Neurosci Bull. 2011 Dec;27(6):413-21
22108818
BMC Bioinformatics. 2010 Jan 14;11:27
20070912
Nat Genet. 2006 Aug;38(8):904-9
16862161
Bioinformatics. 2013 Sep 1;29(17):2211-2
23825367
Nature. 2014 Mar 27;507(7493):462-70
24670764
Bioinformatics. 2015 Jul 1;31(13):2123-30
25717192
Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
12184808
Nat Genet. 2015 Jun;47(6):569-76
25915600
BMC Bioinformatics. 2012 Jun 18;13:134
22708584
J Neurosci. 2013 Feb 13;33(7):2732-53
23407934
Trends Genet. 2013 Oct;29(10):569-74
23810203
BMC Bioinformatics. 2008 Jun 09;9:271
18541026
Dev Cell. 2014 Sep 29;30(6):688-700
25241935
Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13891-6
15353588
Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12698-703
20616000
Nature. 2012 Nov 1;491(7422):119-24
23128233
J Biomed Inform. 2010 Dec;43(6):932-44
20619355
Genome Biol. 2008;9(2):R26
18248669
Brief Bioinform. 2007 Jan;8(1):2-5
16951416
Cell Stem Cell. 2007 Oct 11;1(4):428-42
18371379
Nature. 2011 Nov 30;480(7376):201-8
22139419
J Neurosci. 2014 Sep 3;34(36):11929-47
25186741
Curr Opin Immunol. 2013 Oct;25(5):571-8
24148234
Neuropsychopharmacology. 2001 Jul;25(1):1-27
11377916
Nat Methods. 2011 Oct 09;8(11):945-7
21983921
Nat Genet. 2011 Oct 09;43(11):1066-73
21983784
Genome Biol. 2009;10(12):R139
19961599
PLoS One. 2012;7(12):e51141
23226565
Gastroenterology. 2011 Nov;141(5):1762-72
21889923
BMC Bioinformatics. 2013 Mar 07;14:89
23497278
Nature. 2012 Sep 20;489(7416):391-9
22996553
PLoS Genet. 2009 Jun;5(6):e1000534
19557189
Genome Res. 2013 Nov;23(11):1862-73
23950145
Nature. 2014 Nov 13;515(7526):264-8
25391964
Nat Neurosci. 2008 Nov;11(11):1271-82
18849986
Nat Neurosci. 2006 Jan;9(1):99-107
16369481
PLoS Comput Biol. 2009 Jun;5(6):e1000417
19543383
Bioinformatics. 2007 Oct 15;23(20):2692-9
17724061
J Am Soc Nephrol. 2008 Apr;19(4):667-71
18287559
Nat Biotechnol. 2010 Apr;28(4):322-4
20379172
Nat Neurosci. 2014 Jan;17(1):131-43
24316888
Nature. 2012 Dec 20;492(7429):369-75
23222517
Infect Genet Evol. 2012 Jul;12(5):913-21
21930246
Biol Rev Camb Philos Soc. 2006 Aug;81(3):425-55
16790079
PLoS One. 2011 Jan 27;6(1):e16493
21304595
PLoS Genet. 2014 Jan;10(1):e1004006
24391511
Am J Gastroenterol. 2004 May;99(5):938-45
15128364
PLoS One. 2011;6(9):e24640
21931791
BMC Med Genomics. 2013;6 Suppl 1:S10
23369200