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Supplementary Information

Gene-expression patterns in drug resistant acute lymphoblastic leukemia cells and response to treatment.

Supplemental Table 3 : Permutation analysis and false discovery rate of probe sets selected by Wilcoxon rank sum test and t-test.

Permutation analysis (N=1000) was computed for each dataset (prednisolone (PRED), vincristine (VCR), asparaginase (ASP), daunorubicin (DNR) using (a) all patients and (b) only patients with B-lineage acute lymphoblastic leukemia. For each P-value (α) using Wilcoxon rank sum test, the number of probe sets (N), the false discovery rate (FDR) and the P-value are listed. Numbers in red indicate the subset of genes chosen for further analyses  (Supplemental Table 4) based on a low P-value, an FDR less than 10 percent when possible, and between 25 and 100 genes for each drug. Similar results were obtained with probe sets selected by t-test using (c) all patients and (d) only patients with B-lineage.

a. All Patients

  α = 0.0001 α = 0.0005 α = 0.001

drug

N

FDR [%]

P-value

N

FDR [%]

P-value

N

FDR [%]

P-value

PRED

11

10

0.021

32

18

0.017

53

22

0.019

VCR

7

13

0.028

76

15

<0.001

76

16

<0.001

ASP

24

5

0.007

91

6

<0.001

135

9

<0.001

DNR

2

22

0.060

11

45

0.080

27

45

0.065

b. B-lineage

  α = 0.0001 α = 0.0005 α = 0.001

drug

N

FDR [%]

P-value

N

FDR [%]

P-value

N

FDR [%]

P-value

PRED

19

6

0.007

57

10

0.002

92

13

0.003

VCR

22

6

0.004

74

8

<0.001

138

10

<0.001

ASP

67

2

0.002

202

3

<0.001

279

4

<0.001

DNR

5

22

0.029

25

26

0.011

38

32

0.014

c. All patients

  α = 0.0001 α = 0.0005 α = 0.001

drug

N

FDR [%]

P-value

N

FDR [%]

P-value

N

FDR [%]

P-value

PRED

10

12

0.058

33

17

0.021

49

24

0.034

VCR

7

8

0.032

55

11

0.012

91

13

0.012

ASP

21

5

0.028

84

7

<0.001

120

9

<0.001

DNR

3

29

0.556

19

34

0.188

34

37

0.164

d. B-lineage

  α = 0.0001 α = 0.0005 α = 0.001

drug

N

FDR [%]

P-value

N

FDR [%]

P-value

N

FDR [%]

P-value

PRED

26

4

0.014

69

8

0.003

98

12

0.003

VCR

33

3

0.016

101

5

<0.001

166

7

<0.001

ASP

71

2

<0.001

184

3

<0.001

269

4

<0.001

DNR

8

12

0.140

34

18

0.043

50

26

0.068

In each random permutation, the class label (resistant or sensitive) was randomly assigned to each patient and genes were reselected using Wilcoxon rank sum test and t-test based on the random labels. The overall significance (Pα) of the model was estimated using the following formula:

table 3

Where α is the P-value using Wilcoxon rank sum test or t-test; q-valueαrandom is estimated q-value given a using random class label; q-valueαobs is the observed q-value given α using the observed class label.

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