St. Jude Children's Research: ALL4

	Supplementary Information for:
	Gene-expression patterns in drug resistant acute lymphoblastic leukemia cells and response to treatment. Amy Holleman, Meyling H. Cheok, Monique L. den Boer, Wenjian Yang, Anjo J.P. Veerman, Karin M. Kazemier, Deqing Pei, Cheng Cheng, Ching-Hon Pui, Mary V. Relling, Gritta E. Janka-Schaub, Rob Pieters, and William E. Evans

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 (P_α) of the model was estimated using the following formula:

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