Gene set
All glioma positive enrichment
Function
SABATES_COLORECTAL_ADENOMA_UP
GSE3982_EOSINOPHIL_VS_CENT_MEMORY_CD4_TC
ELL_DN
V$AP2GAMMA_01
WIERENGA_STAT5A_TARGETS_UP
KEGG_PROXIMAL_TUBULE_BICARBONATE_RECLAM
ATION
GSE13306_LAMINA_PROPRIA_VS_SPLEEN_TREG_D
N
GSE13484_12H_VS_3H_YF17D_VACCINE_STIM_PB
MC_DN
MODULE_206
PID_IL27PATHWAY
LEIN_OLIGODENDROCYTE_MARKERS
SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTIO
N
GSE17721_CPG_VS_GARDIQUIMOD_12H_BMDM_D
N
SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP
LEIN_CHOROID_PLEXUS_MARKERS
GSE26928_EFF_MEM_VS_CENTR_MEM_CD4_TCELL
_UP
V$IK2_01
PURINE_NUCLEOTIDE_BINDING
YOKOE_CANCER_TESTIS_ANTIGENS
NUCLEOTIDE_BINDING
MODULE_323
Cancer-related genes
N Genes
ES
NES
PGSEA
FDR q
FWER q
76
0.22
2.28
0.00
1.00
0.97
103
131
100
0.18
0.16
0.18
2.20
2.18
2.18
0.00
0.00
0.00
1.00
1.00
1.00
0.99
1.00
1.00
Blood acidity level
15
0.46
2.09
0.00
1.00
1.00
Immune regulation
111
0.17
2.06
0.00
1.00
1.00
Immune regulation
Cancer-related genes
Immune regulation
Expressed in brain cells
90
79
16
35
0.19
0.20
0.42
0.28
2.05
2.04
2.03
2.00
0.00
0.00
0.00
0.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
Cell signalling
48
0.24
1.99
0.01
1.00
1.00
Immune response
Viral/immune response
Expressed in brain
98
41
68
0.17
0.26
0.19
1.98
1.95
1.92
0.00
0.01
0.01
1.00
1.00
1.00
1.00
1.00
1.00
105
144
114
19
122
35
0.16
0.14
0.15
0.37
0.15
0.27
1.91
1.90
1.90
1.89
1.89
1.89
0.01
0.01
0.01
0.01
0.01
0.01
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
Immune regulation
Development/retinoic acid regulation
Cell-fate decision making
Immune regulation
Regulated by unknown transcription factor
DNA replication/repair
Cancer-related genes
DNA replication/repair
Brain immune regulation
All glioma negative enrichment
GSE17721_LPS_VS_GARDIQUIMOD_6H_BMDM_UP
REACTOME_RESPONSE_TO_ELEVATED_PLATELET_C
YTOSOLIC_CA2_
GSE360_CTRL_VS_B_MALAYI_HIGH_DOSE_DC_UP
ALCALAY_AML_BY_NPM1_LOCALIZATION_DN
GSE3982_MEMORY_CD4_TCELL_VS_BCELL_UP
KERLEY_RESPONSE_TO_CISPLATIN_UP
UNFOLDED_PROTEIN_BINDING
SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_
UP
GSE37416_12H_VS_24H_F_TULARENSIS_LVS_NEUT
ROPHIL_UP
OUILLETTE_CLL_13Q14_DELETION_UP
METALLOENDOPEPTIDASE_ACTIVITY
REACTOME_GAB1_SIGNALOSOME
CALCIUM_ION_BINDING
BASAKI_YBX1_TARGETS_DN
PID_P75NTRPATHWAY
WANG_CLASSIC_ADIPOGENIC_TARGETS_OF_PPARG
FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STAB
LE_UP
NEGATIVE_REGULATION_OF_NUCLEOBASENUCLEOS
IDENUCLEOTIDE_AND_NUCLEIC_ACID_METABOLIC_
PROCESS
RODWELL_AGING_KIDNEY_UP
MORF_EIF3S6
Viral/immune response
112
-0.22
-2.78
0.00
0.08
0.07
Clotting regulation
Parasite/immune response
Stem-cell renewal
Immune regulation
Response to cancer treatment
Stress response
46
103
101
110
24
23
-0.31
-0.21
-0.22
-0.20
-0.41
-0.40
-2.53
-2.49
-2.49
-2.47
-2.36
-2.31
0.00
0.00
0.00
0.00
0.00
0.00
0.28
0.25
0.19
0.19
0.33
0.41
0.40
0.48
0.50
0.57
0.84
0.93
Invasiveness in breast cancer
82
-0.21
-2.27
0.00
0.46
0.97
113
39
18
20
66
199
35
17
-0.18
-0.30
-0.45
-0.41
-0.22
-0.13
-0.30
-0.44
-2.24
-2.23
-2.23
-2.19
-2.18
-2.15
-2.14
-2.13
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.53
0.48
0.46
0.54
0.52
0.58
0.58
0.61
0.99
0.99
0.99
1.00
1.00
1.00
1.00
1.00
95
-0.18
-2.07
0.01
0.79
1.00
107
264
45
-0.17
-0.11
-0.26
-2.06
-2.06
-2.06
0.01
0.01
0.00
0.82
0.79
0.75
1.00
1.00
1.00
Bacterial/immune response
CLL-related genes
Essential enzyme activity
Cell-growth signalling
Cell signalling
Ovarian cancer-related genes
Neuronal survival/differentiation
Fat-cell differentiation
Ewing's sarcoma-related genes
Nucleic acid metabolism
Ageing in kidney
Protein synthesis
GBM positive enrichment
KEGG_AMINO_SUGAR_AND_NUCLEOTIDE_SUGAR
_METABOLISM
GAVIN_FOXP3_TARGETS_CLUSTER_P6
MODULE_239
SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3
GSE22886_IL2_VS_IL15_STIM_NKCELL_DN
GSE12845_IGD_POS_BLOOD_VS_PRE_GC_TONSIL_B
CELL_UP
GSE17721_CPG_VS_GARDIQUIMOD_24H_BMDM_U
P
GSE36392_TYPE_2_MYELOID_VS_NEUTROPHIL_IL25
_TREATED_LUNG_UP
RESPONSE_TO_LIGHT_STIMULUS
GSE32423_CTRL_VS_IL4_MEMORY_CD8_TCELL_UP
MODULE_345
MORF_PCNA
YANG_BREAST_CANCER_ESR1_BULK_UP
KEGG_BASAL_TRANSCRIPTION_FACTORS
TIEN_INTESTINE_PROBIOTICS_6HR_DN
ZHENG_RESPONSE_TO_ARSENITE_DN
WCAANNNYCAG_UNKNOWN
GSE17721_POLYIC_VS_PAM3CSK4_24H_BMDM_UP
SCHRAETS_MLL_TARGETS_UP
MODULE_206
Glycolysis, DNA repair
T-cell immune cell regulation
Liver cancer-related genes
Liver cancer-related genes
Immune response to viral infection
26
57
65
33
107
0.46
0.29
0.25
0.33
0.18
2.84
2.64
2.34
2.26
2.20
0.00
0.00
0.00
0.00
0.00
0.04
0.11
0.68
0.91
1.00
0.04
0.19
0.88
0.97
1.00
Immune regulation
100
0.18
2.16
0.00
1.00
1.00
Immune response to viral/bacterial infection
123
0.17
2.16
0.00
1.00
1.00
Immune response - inflammation
Response to light exposure (can be important
in cancer e.g. phytochemotherapy)
Activation of immune response (adaptive
immunity)
Immune response
DNA replication/repair
Hormone resistant breast cancer (affects cell
cycle, apoptosis, DNA repair)
Gene expression regulation
Immune response to bacteria
DNA damage response/DNA repair
Regulated by unknown transcription factor
Anti-viral immune response
Epigenetic regulation
Breast cancer-related genes
111
0.17
2.15
0.00
0.96
1.00
27
0.34
2.12
0.00
1.00
1.00
92
71
28
0.19
0.21
0.33
2.11
2.11
2.10
0.00
0.01
0.00
0.97
0.90
0.86
1.00
1.00
1.00
15
19
90
15
127
116
18
82
0.46
0.41
0.18
0.43
0.16
0.16
0.40
0.20
2.10
2.10
2.08
2.08
2.07
2.05
2.05
2.04
0.00
0.00
0.01
0.00
0.00
0.01
0.00
0.00
0.80
0.75
0.80
0.76
0.73
0.79
0.77
0.77
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
GBM negative enrichment
GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENIT
OR_DN
GENERATION_OF_PRECURSOR_METABOLITES_AND
_ENERGY
BROWNE_HCMV_INFECTION_30MIN_DN
HOLLEMAN_VINCRISTINE_RESISTANCE_ALL_UP
CHR8Q13
PID_NOTCH_PATHWAY
GSE11864_UNTREATED_VS_CSF1_IFNG_IN_MAC_U
P
PID_ATF2_PATHWAY
SWEET_KRAS_ONCOGENIC_SIGNATURE
PEROXISOME
RHODOPSIN_LIKE_RECEPTOR_ACTIVITY
MICROBODY
GSE24142_EARLY_THYMIC_PROGENITOR_VS_DN3_
THYMOCYTE_ADULT_DN
PID_MYC_ACTIVPATHWAY
FIGUEROA_AML_METHYLATION_CLUSTER_3_UP
YOSHIOKA_LIVER_CANCER_EARLY_RECURRENCE_D
N
POTASSIUM_ION_TRANSPORT
KEGG_FC_GAMMA_R_MEDIATED_PHAGOCYTOSIS
YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_C
LUSTER_1
Non-GBM positive enrichment
Tumour supressor/Ras oncogene/translational
control
29
-0.36
-2.38
0.00
1.00
0.80
Metabolism
Response to viral infection
Cell division/growth
Genes in 8q13
Notch signalling (proliferation/differentiation
70
83
20
23
34
-0.24
-0.21
-0.43
-0.38
-0.30
-2.32
-2.32
-2.30
-2.16
-2.09
0.00
0.00
0.00
0.00
0.00
1.00
0.82
0.68
1.00
1.00
0.91
0.91
0.94
1.00
1.00
Immune activation
Stress response/apoptosis
K-Ras oncogenic signalling
Metabolism
Signal transduction
Metabolism
92
30
38
31
72
31
-0.18
-0.31
-0.28
-0.31
-0.20
-0.31
-2.06
-2.05
-2.05
-2.04
-2.04
-2.04
0.01
0.00
0.01
0.00
0.00
0.01
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
T cell differentiation
Targets of oncogene c-Myc
(proliferation/differentiation)
AML-related genes
92
-0.18
-2.02
0.00
1.00
1.00
46
84
-0.25
-0.19
-2.02
-2.02
0.00
0.00
1.00
1.00
1.00
1.00
Liver cancer recurrence
Neuro-transmission
Phagocytosis
36
32
53
-0.28
-0.30
-0.23
-2.02
-2.01
-2.01
0.01
0.01
0.00
1.00
1.00
1.00
1.00
1.00
1.00
Progesterone signalling
42
-0.26
-2.00
0.01
0.98
1.00
V$HEN1_01
CLASPER_LYMPHATIC_VESSELS_DURING_METASTAS
IS_DN
CHR16Q23
ERB2_UP.V1_UP
CHESLER_BRAIN_HIGHEST_GENETIC_VARIANCE
GSE17974_0H_VS_1H_IN_VITRO_ACT_CD4_TCELL_
UP
GSE13485_DAY3_VS_DAY7_YF17D_VACCINE_PBMC
_UP
PEDRIOLI_MIR31_TARGETS_UP
GSE37416_0H_VS_3H_F_TULARENSIS_LVS_NEUTRO
PHIL_DN
ICHIBA_GRAFT_VERSUS_HOST_DISEASE_35D_DN
GSE360_L_MAJOR_VS_B_MALAYI_LOW_DOSE_MAC
_UP
GSE32423_IL7_VS_IL4_MEMORY_CD8_TCELL_DN
GSE25087_FETAL_VS_ADULT_TREG_DN
MISSIAGLIA_REGULATED_BY_METHYLATION_UP
LINDGREN_BLADDER_CANCER_CLUSTER_1_DN
GSE9037_WT_VS_IRAK4_KO_LPS_1H_STIM_BMDM
_UP
GSE16522_ANTI_CD3CD28_STIM_VS_UNSTIM_ME
MORY_CD8_TCELL_DN
V$TFIIA_Q6
CHR12P11
REACTOME_ABC_FAMILY_PROTEINS_MEDIATED_TR
ANSPORT
Non-GBM negative enrichment
GSE17721_LPS_VS_POLYIC_24H_BMDM_DN
Cell growth, development
99
0.23
2.66
0.00
0.17
0.17
19
16
112
18
0.43
0.47
0.17
0.41
2.27
2.24
2.14
2.13
0.00
0.00
0.00
0.00
1.00
1.00
1.00
1.00
0.98
0.99
1.00
1.00
87
0.19
2.10
0.00
1.00
1.00
Immune response to yellow fever virus
Tumour supressor
76
108
0.20
0.17
2.07
2.06
0.01
0.00
1.00
1.00
1.00
1.00
Immune response to bacterial infection
Immune regulation
114
30
0.16
0.31
2.02
2.00
0.01
0.00
1.00
1.00
1.00
1.00
97
99
90
0.17
0.17
0.17
1.99
1.99
1.98
0.00
0.01
0.01
1.00
1.00
1.00
1.00
1.00
1.00
Downregulated in metastasis
genes in 16q23, commonly lost in gliomas
estrogen signalling - gene regulation
Expressed in brain
T cell differentiation
Immune response to parasite
Immune regulation
Immune regulation
Regulated by methylation, response to DNA
hypomethylating chemotherapy drug
downregulated in kidney cancer (e.g.
candidate tumour suppressors)
64
0.21
1.97
0.01
1.00
1.00
212
0.12
1.96
0.00
1.00
1.00
Immune response to bacterial infection
116
0.15
1.95
0.01
1.00
1.00
Immune response
Transcriptional control
Genes in 12p11, loss previously observed in
gliomas
DNA repair/tumour therapy
resitance/translation
114
128
0.15
0.14
1.93
1.90
0.00
0.01
1.00
1.00
1.00
1.00
18
0.37
1.90
0.01
1.00
1.00
20
0.35
1.90
0.00
1.00
1.00
Immune response to viruses/bacteria
107
-0.22
-2.54
0.00
0.48
0.36
V$VDR_Q3
JECHLINGER_EPITHELIAL_TO_MESENCHYMAL_TRAN
SITION_DN
GSE17721_LPS_VS_GARDIQUIMOD_6H_BMDM_UP
GSE24142_DN2_VS_DN3_THYMOCYTE_ADULT_UP
GSE3982_EOSINOPHIL_VS_MAST_CELL_DN
PARK_TRETINOIN_RESPONSE_AND_PML_RARA_FUS
ION
GSE17721_LPS_VS_POLYIC_0.5H_BMDM_UP
GSE1448_ANTI_VALPHA2_VS_VBETA5_DP_THYMOC
YTE_DN
POTTI_5FU_SENSITIVITY
KIM_WT1_TARGETS_8HR_DN
AGUIRRE_PANCREATIC_CANCER_COPY_NUMBER_D
N
GSE17721_PAM3CSK4_VS_GADIQUIMOD_8H_BMD
M_UP
ALCALAY_AML_BY_NPM1_LOCALIZATION_DN
AIYAR_COBRA1_TARGETS_DN
GSE37416_CTRL_VS_6H_F_TULARENSIS_LVS_NEUT
ROPHIL_DN
WATANABE_RECTAL_CANCER_RADIOTHERAPY_RES
PONSIVE_UP
BOYAULT_LIVER_CANCER_SUBCLASS_G123_UP
GSE1460_INTRATHYMIC_T_PROGENITOR_VS_DP_T
HYMOCYTE_DN
EXCRETION
Regulated by Vitamin D
Negative regulators of
metastasis/invasiveness
Immune response to viruses/bacteria
Immune regulation
Immune regulation
Retinoic acid signalling (differentiation,
apoptosis)
Immune response to viruses/bacteria
111
-0.20
-2.41
0.00
0.68
0.73
38
115
105
102
-0.32
-0.19
-0.19
-0.18
-2.33
-2.30
-2.23
-2.11
0.00
0.00
0.00
0.00
0.78
0.76
0.95
1.00
0.89
0.95
0.99
1.00
18
112
-0.42
-0.17
-2.09
-2.07
0.00
0.00
1.00
1.00
1.00
1.00
Immune response
genes sensitive to 5-FU chemotherapy (blocks
DNA replication)
Regulated by WT1 (expressed in gliomas)
106
-0.17
-2.05
0.00
1.00
1.00
17
71
-0.42
-0.21
-2.05
-2.05
0.00
0.01
1.00
1.00
1.00
1.00
Pancreatic cancer-related genes
127
-0.15
-2.04
0.01
1.00
1.00
immune response to viruses/bacteria
Stem-cell renewal
DNA repair
105
100
20
-0.17
-0.17
-0.38
-2.03
-2.02
-2.00
0.00
0.00
0.00
1.00
1.00
1.00
1.00
1.00
1.00
Bacterial immune response
93
-0.18
-2.00
0.00
1.00
1.00
Response to radiotherapy
Liver cancer-related genes
56
24
-0.22
-0.34
-2.00
-1.99
0.00
0.01
1.00
1.00
1.00
1.00
101
23
-0.17
-0.34
-1.98
-1.97
0.01
0.00
1.00
1.00
1.00
1.00
Immune regulation
Metabolism
Supplementary Table 5: Gene-set enrichment analysis (GSEA) of glioma-associated genes. GSEA was performed on gene-based SKAT P values
generated for all glioma as well as GBM and non-GBM subtypes. “Positive enrichment” corresponds to gene sets enriched for positively
associated (low SKAT P value) genes, “Negative enrichment” corresponds to gene sets enriched for negatively-associated (high SKAT P value)
genes. Gene sets in bold are those passing advocated thresholds (i.e. PGSEA < 0.05, FDR q < 0.25). ES, effect size; NES, normalised effect size;
FDR, false discovery rate; FWER, family-wise error rate.