This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 19702 genes and 15 clinical features across 474 samples, statistically thresholded by Q value < 0.05, 14 clinical features related to at least one genes.
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6 genes correlated to 'Time to Death'.
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FAM118B__1 , SYNGR3 , KLHL29 , SYN2__1 , ANKRD53 , ...
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345 genes correlated to 'AGE'.
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MGA , NHLRC1 , INA , RANBP17 , C1ORF59 , ...
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280 genes correlated to 'NEOPLASM.DISEASESTAGE'.
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OTOS , C1ORF91__1 , EIF3I__1 , ACTA1 , C10ORF137 , ...
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104 genes correlated to 'PATHOLOGY.T.STAGE'.
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TBKBP1 , GJD3 , IFT140 , TMEM204 , PDGFB , ...
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1118 genes correlated to 'PATHOLOGY.N.STAGE'.
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CPNE1__1 , RBM12__1 , PON2 , DAGLA , BMP1 , ...
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25 genes correlated to 'PATHOLOGY.M.STAGE'.
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C1ORF91__1 , EIF3I__1 , LCA5 , CAPN5__1 , OMP , ...
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27 genes correlated to 'GENDER'.
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ALG11__2 , UTP14C__1 , ETF1 , KIF4B , FAM35A , ...
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2303 genes correlated to 'HISTOLOGICAL.TYPE'.
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PON2 , EMP1 , C8ORF73 , SLC6A12 , LAMP3 , ...
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45 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
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SIK1 , SNX31 , STX17 , KIAA1143__1 , KIF15__1 , ...
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47 genes correlated to 'RADIATIONEXPOSURE'.
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CHEK2 , HSCB , MGC21881 , CASP12 , TMEM63C , ...
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329 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.
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OTOS , DEFB131 , TBX19 , SLC16A3 , PA2G4P4 , ...
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7 genes correlated to 'COMPLETENESS.OF.RESECTION'.
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ANKRD34B , CAPN5__1 , OMP , C17ORF108 , KCNJ14 , ...
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1004 genes correlated to 'NUMBER.OF.LYMPH.NODES'.
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FUT2 , MET , TMEM173 , TAGLN2 , MACF1 , ...
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1 gene correlated to 'TUMOR.SIZE'.
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TGFBR1
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No genes correlated to 'MULTIFOCALITY'
Complete statistical result table is provided in Supplement Table 1
Table 1. Get Full Table This table shows the clinical features, statistical methods used, and the number of genes that are significantly associated with each clinical feature at Q value < 0.05.
Clinical feature | Statistical test | Significant genes | Associated with | Associated with | ||
---|---|---|---|---|---|---|
Time to Death | Cox regression test | N=6 | shorter survival | N=4 | longer survival | N=2 |
AGE | Spearman correlation test | N=345 | older | N=343 | younger | N=2 |
NEOPLASM DISEASESTAGE | ANOVA test | N=280 | ||||
PATHOLOGY T STAGE | Spearman correlation test | N=104 | higher stage | N=59 | lower stage | N=45 |
PATHOLOGY N STAGE | t test | N=1118 | class1 | N=97 | class0 | N=1021 |
PATHOLOGY M STAGE | ANOVA test | N=25 | ||||
GENDER | t test | N=27 | male | N=13 | female | N=14 |
HISTOLOGICAL TYPE | ANOVA test | N=2303 | ||||
RADIATIONS RADIATION REGIMENINDICATION | t test | N=45 | yes | N=23 | no | N=22 |
RADIATIONEXPOSURE | t test | N=47 | yes | N=23 | no | N=24 |
EXTRATHYROIDAL EXTENSION | ANOVA test | N=329 | ||||
COMPLETENESS OF RESECTION | ANOVA test | N=7 | ||||
NUMBER OF LYMPH NODES | Spearman correlation test | N=1004 | higher number.of.lymph.nodes | N=20 | lower number.of.lymph.nodes | N=984 |
MULTIFOCALITY | t test | N=0 | ||||
TUMOR SIZE | Spearman correlation test | N=1 | higher tumor.size | N=1 | lower tumor.size | N=0 |
Table S1. Basic characteristics of clinical feature: 'Time to Death'
Time to Death | Duration (Months) | 0-158.8 (median=14.1) |
censored | N = 456 | |
death | N = 13 | |
Significant markers | N = 6 | |
associated with shorter survival | 4 | |
associated with longer survival | 2 |
Table S2. Get Full Table List of 6 genes significantly associated with 'Time to Death' by Cox regression test
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
FAM118B__1 | 0 | 6.112e-07 | 0.012 | 0.229 |
SYNGR3 | 171 | 1.087e-06 | 0.021 | 0.743 |
KLHL29 | 0 | 1.403e-06 | 0.028 | 0.235 |
SYN2__1 | 331 | 1.634e-06 | 0.032 | 0.858 |
ANKRD53 | 391 | 2.382e-06 | 0.047 | 0.64 |
LOC150786 | 59001 | 2.531e-06 | 0.05 | 0.88 |
Figure S1. Get High-res Image As an example, this figure shows the association of FAM118B__1 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 6.11e-07 with univariate Cox regression analysis using continuous log-2 expression values.

Table S3. Basic characteristics of clinical feature: 'AGE'
AGE | Mean (SD) | 46.98 (16) |
Significant markers | N = 345 | |
pos. correlated | 343 | |
neg. correlated | 2 |
Table S4. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
MGA | 0.5317 | 6.065e-36 | 1.19e-31 |
NHLRC1 | 0.494 | 1.576e-30 | 3.1e-26 |
INA | 0.4853 | 2.27e-29 | 4.47e-25 |
RANBP17 | 0.4594 | 4.023e-26 | 7.93e-22 |
C1ORF59 | 0.4558 | 1.083e-25 | 2.13e-21 |
ACN9 | 0.4526 | 2.611e-25 | 5.14e-21 |
SYNGR3 | 0.4478 | 9.432e-25 | 1.86e-20 |
ZNF518B | 0.4422 | 4.148e-24 | 8.17e-20 |
NTNG2 | 0.4242 | 3.968e-22 | 7.81e-18 |
OTUD7A | 0.4242 | 4.004e-22 | 7.88e-18 |
Figure S2. Get High-res Image As an example, this figure shows the association of MGA to 'AGE'. P value = 6.06e-36 with Spearman correlation analysis. The straight line presents the best linear regression.

Table S5. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'
NEOPLASM.DISEASESTAGE | Labels | N |
STAGE I | 271 | |
STAGE II | 48 | |
STAGE III | 106 | |
STAGE IV | 2 | |
STAGE IVA | 41 | |
STAGE IVC | 4 | |
Significant markers | N = 280 |
Table S6. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'
ANOVA_P | Q | |
---|---|---|
OTOS | 7.576e-30 | 1.49e-25 |
C1ORF91__1 | 1.605e-29 | 3.16e-25 |
EIF3I__1 | 1.605e-29 | 3.16e-25 |
ACTA1 | 1.446e-26 | 2.85e-22 |
C10ORF137 | 6.644e-23 | 1.31e-18 |
LCA5 | 5.937e-22 | 1.17e-17 |
C2ORF34 | 4.26e-17 | 8.39e-13 |
PREPL | 4.26e-17 | 8.39e-13 |
RABL2A | 1.121e-15 | 2.21e-11 |
RPL23AP7 | 1.121e-15 | 2.21e-11 |
Figure S3. Get High-res Image As an example, this figure shows the association of OTOS to 'NEOPLASM.DISEASESTAGE'. P value = 7.58e-30 with ANOVA analysis.

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'
PATHOLOGY.T.STAGE | Mean (SD) | 2.12 (0.88) |
N | ||
1 | 138 | |
2 | 157 | |
3 | 158 | |
4 | 19 | |
Significant markers | N = 104 | |
pos. correlated | 59 | |
neg. correlated | 45 |
Table S8. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
TBKBP1 | 0.3038 | 1.564e-11 | 3.08e-07 |
GJD3 | 0.2934 | 7.97e-11 | 1.57e-06 |
IFT140 | 0.2928 | 8.698e-11 | 1.71e-06 |
TMEM204 | 0.2928 | 8.698e-11 | 1.71e-06 |
PDGFB | 0.2836 | 3.506e-10 | 6.91e-06 |
CKMT2 | 0.2814 | 4.883e-10 | 9.62e-06 |
RNU5D__1 | 0.2814 | 4.883e-10 | 9.62e-06 |
RNU5E__1 | 0.2814 | 4.883e-10 | 9.62e-06 |
FLJ42875 | 0.2662 | 4.254e-09 | 8.38e-05 |
GGT7 | 0.263 | 6.603e-09 | 0.00013 |
Figure S4. Get High-res Image As an example, this figure shows the association of TBKBP1 to 'PATHOLOGY.T.STAGE'. P value = 1.56e-11 with Spearman correlation analysis.

Table S9. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'
PATHOLOGY.N.STAGE | Labels | N |
class0 | 213 | |
class1 | 214 | |
Significant markers | N = 1118 | |
Higher in class1 | 97 | |
Higher in class0 | 1021 |
Table S10. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'
T(pos if higher in 'class1') | ttestP | Q | AUC | |
---|---|---|---|---|
CPNE1__1 | -9.34 | 6.484e-19 | 1.28e-14 | 0.7313 |
RBM12__1 | -9.34 | 6.484e-19 | 1.28e-14 | 0.7313 |
PON2 | -9.34 | 7.331e-19 | 1.44e-14 | 0.7275 |
DAGLA | -9.26 | 1.147e-18 | 2.26e-14 | 0.73 |
BMP1 | -9.25 | 1.298e-18 | 2.56e-14 | 0.7277 |
MACF1 | -9.25 | 1.501e-18 | 2.96e-14 | 0.7238 |
STARD5 | -9.11 | 3.643e-18 | 7.18e-14 | 0.7286 |
XDH | -8.97 | 1.276e-17 | 2.51e-13 | 0.716 |
SLC34A2 | -8.93 | 1.341e-17 | 2.64e-13 | 0.7302 |
EPHA4 | -8.92 | 1.966e-17 | 3.87e-13 | 0.7133 |
Figure S5. Get High-res Image As an example, this figure shows the association of CPNE1__1 to 'PATHOLOGY.N.STAGE'. P value = 6.48e-19 with T-test analysis.

Table S11. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'
PATHOLOGY.M.STAGE | Labels | N |
M0 | 258 | |
M1 | 7 | |
MX | 208 | |
Significant markers | N = 25 |
Table S12. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'
ANOVA_P | Q | |
---|---|---|
C1ORF91__1 | 4.859e-15 | 9.57e-11 |
EIF3I__1 | 4.859e-15 | 9.57e-11 |
LCA5 | 1.159e-13 | 2.28e-09 |
CAPN5__1 | 6.68e-10 | 1.32e-05 |
OMP | 6.68e-10 | 1.32e-05 |
RPS10 | 2.882e-09 | 5.68e-05 |
PRPF31 | 1.29e-08 | 0.000254 |
TFPT | 1.29e-08 | 0.000254 |
C2ORF34 | 2.591e-08 | 0.00051 |
PREPL | 2.591e-08 | 0.00051 |
Figure S6. Get High-res Image As an example, this figure shows the association of C1ORF91__1 to 'PATHOLOGY.M.STAGE'. P value = 4.86e-15 with ANOVA analysis.

Table S13. Basic characteristics of clinical feature: 'GENDER'
GENDER | Labels | N |
FEMALE | 351 | |
MALE | 123 | |
Significant markers | N = 27 | |
Higher in MALE | 13 | |
Higher in FEMALE | 14 |
Table S14. Get Full Table List of top 10 genes differentially expressed by 'GENDER'
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
ALG11__2 | 41.78 | 1.331e-154 | 2.62e-150 | 0.9952 |
UTP14C__1 | 41.78 | 1.331e-154 | 2.62e-150 | 0.9952 |
ETF1 | 31.79 | 2.553e-79 | 5.03e-75 | 0.9879 |
KIF4B | -17.82 | 4.254e-46 | 8.38e-42 | 0.9034 |
FAM35A | -11.48 | 1.059e-25 | 2.09e-21 | 0.855 |
GLUD1__1 | -11.48 | 1.059e-25 | 2.09e-21 | 0.855 |
WBP11P1 | 9.53 | 9.178e-18 | 1.81e-13 | 0.8038 |
ANKRD20A4 | 8.64 | 4.741e-16 | 9.34e-12 | 0.7426 |
CCDC121__1 | 7.07 | 1.817e-11 | 3.58e-07 | 0.7057 |
GPN1__1 | 7.07 | 1.817e-11 | 3.58e-07 | 0.7057 |
Figure S7. Get High-res Image As an example, this figure shows the association of ALG11__2 to 'GENDER'. P value = 1.33e-154 with T-test analysis.

Table S15. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'
HISTOLOGICAL.TYPE | Labels | N |
OTHER SPECIFY | 9 | |
THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | 332 | |
THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | 98 | |
THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) | 35 | |
Significant markers | N = 2303 |
Table S16. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'
ANOVA_P | Q | |
---|---|---|
PON2 | 2.343e-43 | 4.62e-39 |
EMP1 | 1.706e-42 | 3.36e-38 |
C8ORF73 | 2.415e-41 | 4.76e-37 |
SLC6A12 | 2.514e-41 | 4.95e-37 |
LAMP3 | 2.937e-41 | 5.79e-37 |
LEPR | 5.396e-41 | 1.06e-36 |
LEPROT | 5.396e-41 | 1.06e-36 |
LOC100126784 | 1.067e-39 | 2.1e-35 |
NAV2__1 | 1.067e-39 | 2.1e-35 |
C5ORF62 | 4.029e-39 | 7.93e-35 |
Figure S8. Get High-res Image As an example, this figure shows the association of PON2 to 'HISTOLOGICAL.TYPE'. P value = 2.34e-43 with ANOVA analysis.

45 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
Table S17. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 14 | |
YES | 460 | |
Significant markers | N = 45 | |
Higher in YES | 23 | |
Higher in NO | 22 |
Table S18. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
SIK1 | 9.54 | 3.426e-19 | 6.75e-15 | 0.6953 |
SNX31 | 8.26 | 3.369e-15 | 6.64e-11 | 0.7016 |
STX17 | 9.26 | 1.128e-13 | 2.22e-09 | 0.634 |
KIAA1143__1 | 8.9 | 2.543e-13 | 5.01e-09 | 0.7422 |
KIF15__1 | 8.9 | 2.543e-13 | 5.01e-09 | 0.7422 |
TAF7 | 7.78 | 3.849e-13 | 7.58e-09 | 0.7023 |
MYOM2 | 7.94 | 5.474e-12 | 1.08e-07 | 0.5366 |
HORMAD1 | -8.56 | 3.131e-11 | 6.17e-07 | 0.7278 |
ZNHIT3 | 7.08 | 1.078e-10 | 2.12e-06 | 0.562 |
CBLN1 | 7.22 | 1.611e-10 | 3.17e-06 | 0.7325 |
Figure S9. Get High-res Image As an example, this figure shows the association of SIK1 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 3.43e-19 with T-test analysis.

Table S19. Basic characteristics of clinical feature: 'RADIATIONEXPOSURE'
RADIATIONEXPOSURE | Labels | N |
NO | 400 | |
YES | 17 | |
Significant markers | N = 47 | |
Higher in YES | 23 | |
Higher in NO | 24 |
Table S20. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONEXPOSURE'
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
CHEK2 | -7.33 | 2.742e-12 | 5.4e-08 | 0.6022 |
HSCB | -7.33 | 2.742e-12 | 5.4e-08 | 0.6022 |
MGC21881 | -7.3 | 1.15e-11 | 2.27e-07 | 0.5853 |
CASP12 | -7.61 | 3.384e-11 | 6.67e-07 | 0.6076 |
TMEM63C | -7.47 | 5.819e-11 | 1.15e-06 | 0.6287 |
HESX1 | 7.19 | 1.291e-10 | 2.54e-06 | 0.6697 |
CYP3A4 | 7.36 | 4.623e-10 | 9.1e-06 | 0.666 |
POLR2F | 7.34 | 5.845e-10 | 1.15e-05 | 0.6754 |
PHKB | 6.54 | 7.862e-10 | 1.55e-05 | 0.7191 |
RAD54B | 7.91 | 1.314e-09 | 2.59e-05 | 0.7494 |
Figure S10. Get High-res Image As an example, this figure shows the association of CHEK2 to 'RADIATIONEXPOSURE'. P value = 2.74e-12 with T-test analysis.

Table S21. Basic characteristics of clinical feature: 'EXTRATHYROIDAL.EXTENSION'
EXTRATHYROIDAL.EXTENSION | Labels | N |
MINIMAL (T3) | 124 | |
MODERATE/ADVANCED (T4A) | 15 | |
NONE | 319 | |
VERY ADVANCED (T4B) | 1 | |
Significant markers | N = 329 |
Table S22. Get Full Table List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'
ANOVA_P | Q | |
---|---|---|
OTOS | 2.782e-73 | 5.48e-69 |
DEFB131 | 3.473e-33 | 6.84e-29 |
TBX19 | 1.341e-23 | 2.64e-19 |
SLC16A3 | 4.797e-21 | 9.45e-17 |
PA2G4P4 | 3.558e-20 | 7.01e-16 |
BTBD12 | 4.612e-20 | 9.08e-16 |
C9ORF46 | 1.652e-17 | 3.25e-13 |
TRAM1L1 | 3.561e-17 | 7.01e-13 |
NPTN | 4.155e-17 | 8.18e-13 |
ISL2 | 4.576e-17 | 9.01e-13 |
Figure S11. Get High-res Image As an example, this figure shows the association of OTOS to 'EXTRATHYROIDAL.EXTENSION'. P value = 2.78e-73 with ANOVA analysis.

Table S23. Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'
COMPLETENESS.OF.RESECTION | Labels | N |
R0 | 369 | |
R1 | 46 | |
R2 | 3 | |
RX | 27 | |
Significant markers | N = 7 |
Table S24. Get Full Table List of 7 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'
ANOVA_P | Q | |
---|---|---|
ANKRD34B | 2.157e-19 | 4.25e-15 |
CAPN5__1 | 7.325e-18 | 1.44e-13 |
OMP | 7.325e-18 | 1.44e-13 |
C17ORF108 | 7.62e-13 | 1.5e-08 |
KCNJ14 | 3.321e-09 | 6.54e-05 |
HPS3 | 2.336e-07 | 0.0046 |
FCRL1 | 1.411e-06 | 0.0278 |
Figure S12. Get High-res Image As an example, this figure shows the association of ANKRD34B to 'COMPLETENESS.OF.RESECTION'. P value = 2.16e-19 with ANOVA analysis.

Table S25. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'
NUMBER.OF.LYMPH.NODES | Mean (SD) | 3.56 (6.2) |
Significant markers | N = 1004 | |
pos. correlated | 20 | |
neg. correlated | 984 |
Table S26. Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
FUT2 | -0.4279 | 2.66e-18 | 5.24e-14 |
MET | -0.424 | 5.672e-18 | 1.12e-13 |
TMEM173 | -0.4189 | 1.564e-17 | 3.08e-13 |
TAGLN2 | -0.4152 | 3.179e-17 | 6.26e-13 |
MACF1 | -0.413 | 4.829e-17 | 9.51e-13 |
CAPN2 | -0.4102 | 8.153e-17 | 1.61e-12 |
STARD5 | -0.4085 | 1.118e-16 | 2.2e-12 |
HDAC9 | -0.405 | 2.163e-16 | 4.26e-12 |
CPNE1__1 | -0.4049 | 2.192e-16 | 4.32e-12 |
RBM12__1 | -0.4049 | 2.192e-16 | 4.32e-12 |
Figure S13. Get High-res Image As an example, this figure shows the association of FUT2 to 'NUMBER.OF.LYMPH.NODES'. P value = 2.66e-18 with Spearman correlation analysis. The straight line presents the best linear regression.

Table S27. Basic characteristics of clinical feature: 'MULTIFOCALITY'
MULTIFOCALITY | Labels | N |
MULTIFOCAL | 214 | |
UNIFOCAL | 250 | |
Significant markers | N = 0 |
Table S28. Basic characteristics of clinical feature: 'TUMOR.SIZE'
TUMOR.SIZE | Mean (SD) | 2.94 (1.6) |
Significant markers | N = 1 | |
pos. correlated | 1 | |
neg. correlated | 0 |
Table S29. Get Full Table List of one gene significantly correlated to 'TUMOR.SIZE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
TGFBR1 | 0.2396 | 2.308e-06 | 0.0455 |
Figure S14. Get High-res Image As an example, this figure shows the association of TGFBR1 to 'TUMOR.SIZE'. P value = 2.31e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

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Expresson data file = THCA-TP.meth.by_min_expr_corr.data.txt
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Clinical data file = THCA-TP.clin.merged.picked.txt
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Number of patients = 474
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Number of genes = 19702
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Number of clinical features = 15
For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels
For continuous numerical clinical features, Spearman's rank correlation coefficients (Spearman 1904) and two-tailed P values were estimated using 'cor.test' function in R
For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R
For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R
For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.