funtooNorm: an R package for normalization of DNA methylation data when there are multiple cell or tissue types.
BACKGROUND
DNA methylation patterns are well known to vary substantially across cell types or tissues. Hence, existing normalization methods may not be optimal if they do not take this into account. We therefore present a new R package for normalization of data from the Illumina Infinium Human Methylation450 BeadChip (Illumina 450 K) built on the concepts in the recently published funNorm method, and introducing cell-type or tissue-type flexibility.


RESULTS
funtooNorm is relevant for data sets containing samples from two or more cell or tissue types. A visual display of cross-validated errors informs the choice of the optimal number of components in the normalization. Benefits of cell (tissue)-specific normalization are demonstrated in three data sets. Improvement can be substantial; it is strikingly better on chromosome X, where methylation patterns have unique inter-tissue variability.


METHODS
An R package is available at https://github.com/GreenwoodLab/funtooNorm, and has been submitted to Bioconductor at http://bioconductor.org.
Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada, Ludmer Center for Neuroinformatics and Mental Health.
Kathleen
K
Oros Klein
Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada, Ludmer Center for Neuroinformatics and Mental Health.
Stepan
S
Grinek
Divisions of Rheumatology and Clinical Epidemiology, McGill University Health Centre, McGill University, Montreal, QC H4A 3J1, Canada.
Sasha
S
Bernatsky
ECOGENE-21, Centre intégré universitaire de santé et de service sociaux du Saguenay-Lac-Saint-Jean, QC G8H 3P7, Canada, Department of Biochemistry, Université de Sherbrooke, QC J1K 2R1, Canada.
Luigi
L
Bouchard
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada.
Antonio
A
Ciampi
Division of Experimental Medicine, McGill University Health Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Ines
I
Colmegna
Department of Biostatistics, Johns Hopkins University, Baltimore, MD 21218, USA.
Jean-Philippe
JP
Fortin
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada.
Long
L
Gao
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA, Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
Marie-France
MF
Hivert
Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada, Department of Medicine, McGill University Health Center, Montreal, QC H4A 3J1, Canada.
Marie
M
Hudson
Canadian Institute for Advanced Research, Child, and Brain Development Program, Toronto, ON M5G 1Z8, Canada, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC V5Z 4H4, Canada, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Michael S
MS
Kobor
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada.
Aurelie
A
Labbe
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC V5Z 4H4, Canada, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Julia L
JL
MacIsaac
Ludmer Center for Neuroinformatics and Mental Health, Canadian Institute for Advanced Research, Child, and Brain Development Program, Toronto, ON M5G 1Z8, Canada, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC V5Z 4H4, Canada, Douglas Mental Health University Institute, McGill University, Montreal, QC H4H 1R3, Canada, Departments of Psychiatry, McGill University, Montreal, QC, Canada H3A 1A1, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 2B4, Canada.
Michael J
MJ
Meaney
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC V5Z 4H4, Canada, Department of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Alexander M
AM
Morin
Douglas Mental Health University Institute, McGill University, Montreal, QC H4H 1R3, Canada.
Kieran J
KJ
O'Donnell
Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada and.
Tomi
T
Pastinen
Centre for Child and Family Studies, Leiden University, Leiden 2300 RB, The Netherlands.
Marinus H
MH
Van Ijzendoorn
Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada, Ludmer Center for Neuroinformatics and Mental Health.
Gregory
G
Voisin
Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada, Department of Biochemistry, Université de Sherbrooke, QC J1K 2R1, Canada, Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A 1A2, Canada, Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada and.
Celia M T
CM
Greenwood
D001327:Autoimmune Diseases / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011247:Pregnancy; D012984:Software