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Tumor progression. Early Adenoma. Hyperplastic Dysplastic. Polyp. Normal. Carcinoma. Metastasis (to Liver). COLON CANCER - TUMOR PROGRESSION:. Colon cancer - global view. First stage : Total of 144 micro-dissected samples Performed on Affymetrix GeneChip U133A (22,283 probe-sets).
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Tumor progression Early Adenoma Hyperplastic Dysplastic Polyp Normal Carcinoma Metastasis (to Liver) COLON CANCER - TUMOR PROGRESSION:
Colon cancer - global view First stage: Total of 144 micro-dissected samples Performed on Affymetrix GeneChip U133A (22,283 probe-sets) 22 Normal colon 24 polyp 47 primary cancer 19 lung metastasis 16 liver metastasis 5 normal lung 11 normal liver
Colon cancer – PCA First stage: Total of 144 micro-dissected samples Performed on Affymetrix GeneChip U133A (22,283 probe-sets) 22 Normal colon 24 polyp 47 primary cancer 19 lung metastasis 16 liver metastasis 5 normal lung 11 normal liver 1st PCA: tissue 2nd PCA: transformation 3rd PCA: muscle/connective contamination 2 of the dominant signals are not relevant
SORTING liver met lung met colon polyp carc. SPIN: MOTIVATION GLOBAL LAYOUT OF DATA IDENTIFY RELEVANT SUBSETS OF GENES SHAPES OF DATA “CLOUDS” DEMONSTRATE ON COLON CANCER DATA
expression levels of 2 genes for 4 patients: • (19) (27) (37) • 9 11 3 • 8 2 4 6 Gene 1 Gene 2 (27) 4 POINTS IN 2-DIMENSIONS: (19) 4 points Gene 2 Gene 1
PCA Projection with Maximal Variance:
PCA leukemia 1 Korsmeyer ALL,AML,MLL 8700 genes Nature 2001
PCA Leukemia 2 Korsmeyer ALL,AML,MLL (In space of 500 most separating genes)
Colon cancer – PCA First stage: Total of 144 micro-dissected samples Performed on Affymetrix GeneChip U133A (22,283 probe-sets) 22 Normal colon 24 polyp 47 primary cancer 19 lung metastasis 16 liver metastasis 5 normal lung 11 normal liver 1st PCA: tissue 2nd PCA: transformation 3rd PCA: muscle/connective contamination 2 of the dominant signals are not relevant
17,300 probes PCA 3 PCA 1 PCA 2 45 samples Cervical Cancer - Gene Expression Matrix 5 Normal cervical tissues 35 Tumors (5 repeats) 5 Cancer cell lines
17,300 probes PCA 3 PCA 1 PCA 2 29 samples Focus on relevant samples Removed the cell lines, the normals, the a6g (29-3) that clustered with the normals; kept 1 of each repeat
(27) (19) 4 points
0.0 2.82 10.0 10.77 2.82 0.0 7.21 8.24 10.0 7.21 0.0 2.82 10.77 8.24 2.82 0.0 (5) (19) (27) (37) toy distmat 0.0 10.0 10.77 2.82 10.0 0.0 2.82 7.21 10.77 2.82 0.0 8.24 2.82 7.21 8.24 0.0 0.0 2.82 10.0 10.77 10.0 7.21 0.0 2.82 10.77 8.24 2.82 0.0 2.82 0.0 7.21 8.24
(5) (19) (27) (37) (5) (37) (19) (27) toy distmat ordered 0.0 10.0 10.77 2.82 10.0 0.0 2.82 7.21 10.77 2.82 0.0 8.24 2.82 7.21 8.24 0.0 0.0 2.82 10.0 10.77 2.82 0.0 7.21 8.24 10.0 7.21 0.0 2.82 10.77 8.24 2.82 0.0
Aug 2000 Bittner Yakhini MDS
glioblastoma 174 genes separate (at FDR of 5%) PrGBM from LGA + ScGBM S Godard, G Getz, H Kobayashi, P Farmer, M Delorenzi, M Nozaki, A-C Diserens, M-F Hamou, P-Y Dietrich, J-G Villemure, R C. Janzer, P Bucher, R Stupp, N de Tribolet, E Domany, M E. Hegi GLIOBLASTOMA: CLONTECH ARRAYS 1185 Genes, 36 Samples 12 Astrocytoma(II) 4 secondary GBM 17 Primary GlioBlastoMa 3 Cell Lines