DNA methylation-based classification of human central...
10
July 5, 2017 DNA methylation-based classification of human central nervous system tumors Martin Sill, German Cancer Research Center (DKFZ)
Transcript of DNA methylation-based classification of human central...
July 5, 2017
DNA methylation-basedclassification of human centralnervous system tumors
Martin Sill, German Cancer Research Center (DKFZ)
DNA methylation / Illumina methylation arrays
0
1
2
3
0.00 0.25 0.50 0.75 1.00
valuede
nsity
variable
STS
LTS
• 450k probes / beta values between 0 and 1
July 5, 2017 Page 2 molecularneuropathology.org
Brain tumor reference set / TSNE
82 tumor classes9 non-tumor classes2801 samples
July 5, 2017 Page 3 molecularneuropathology.org
Random Forest classifier
• variable selection by RF permutated importance measure• subsampling to minority class• ridge-penalized, multinomial GLM for score calibration
July 5, 2017 Page 4 molecularneuropathology.org
Nested 3-fold cross validation
July 5, 2017 Page 5 molecularneuropathology.org
Performance evaluation
MCF PLEXMCF GLM, IDH
MCF MB, G3/4MCF MB, SHH
MCF ENB
MCF GBM
MCF ATRT
MCF LGG, PA
Annotated
Pre
dict
edCross-validation
100
23.2
76.8
78.6
84.4
15.6
3.5
86.7
9.1
7.7
84.6
7.7
GBM, RTK III
GBM, RTK II
GBM, RTK I
GBM, MYCN
GBM, MID
GBM, MES
0 50 100Percent of samples in
annotated class
Raw score Calibrated scoreCalibrated MCF score
Error rate4.89%4.28%1.14%
Brier score0.4440.0700.024
Figure 3
ATRT, MYC
ATRT, SHH
ATRT, TYR
96.6
100 3.45.4
94.6
AUC0.99960.99980.9999
Sensitivity0.9510.9570.989
Specificity0.9990.9990.999
MCF ATRT
MCF Glioblastoma, IDH wildtype
July 5, 2017 Page 6 molecularneuropathology.org
R-package
library(minfi) # basic methylation array analysislibrary(conumee) # copy-number variation analysislibrary(mnp.v11b4)RGset <- read.metharray("path2idats/")MNPreport(RGset)
July 5, 2017 Page 7 molecularneuropathology.org
Interactive copy number variation profile
July 5, 2017 Page 8 molecularneuropathology.org
molecularneuropathology.org
July 5, 2017 Page 9 molecularneuropathology.org
Pediatric Neurooncology DKFZStefan PfisterDavid JonesLukas ChavezDominik Sturm
Biostatistics DKFZAxel BennerAnnette Kopp-Schneider
Neuropathology HeidelbergAndreas von DeimlingDavid CapperDaniel SchrimpfDamian StichelFelix Sahm
Broad InstituteVolker Hovestadt
Genomics and Proteomics Core FacilityDKFZMatthias SchickMelanie Bewerunge-HudlerOliver HeilRoger Fischer
July 5, 2017 Page 10 molecularneuropathology.org
