. 2020 Feb 26;36(11):3537–3548. doi: 10.1093/bioinformatics/btaa126

Table 2.

Summary of transcriptomic drivers of MRI traits in GBM patients

Transcriptomic drivers

Theme	Gene set (collection,^a query^b)	AUC	AP	See also
Enhancing
Growth/death	Growth (G, PTEN)	0.86	0.84
Growth/death	Sensory organ development (G, EGFR, KCNK3)	0.85	0.84	Gutman et al. (2013); Jamshidi et al. (2014)
Immune system	IL2/STAT5 signaling (H)	0.77	0.76
	Complement system (H)	0.79	0.75
	Activation of immune response (G, PTEN)	0.90	0.89
	Leukocyte and lymphocyte activation (G, PIK3R1)	0.85^c	0.84^c
	Immune effector process (G, PIK3CA)	0.87	0.84
Hormones	Early and late responses to estrogen (H)	0.79^c	0.73^c
	Response to steroid hormone (G, RBI)	0.88	0.88
	Reg. of hormone levels (G, PARK2)	0.87	0.84
ECM	Related to ECM proteins (C, ECM)	0.81^c	0.75^c	Diehn et al. (2008)
ECM	Apical junction (H)	0.80	0.75
Vasculature	Heme metabolism (H)	0.77	0.65
Vasculature	Vasculature and heart development (G, LTBP1)	0.80^c	0.79^c	Gutman et al. (2013)
Kinase activity	Multiple (G, EGFR, LTBP1, KCNK3)	0.87^c	0.85^c	Gutman et al. (2013); Jamshidi et al. (2014)
Edema
EMT	EMT (H)	0.80	0.80
	Positive reg. of locomotion (G, EGFR, POSTN)	0.80	0.81	Zinn et al. (2011)
	Taxis (G, CXCL12, KIF5C)	0.80	0.80	Zinn et al. (2011)
	Apical junction (H)	0.77	0.74
	Related to cell adhesion (G, CDKN2A, CTNNA2)	0.79^c	0.80^c	Zinn et al. (2011)
Growth/death	p53 pathway (H)	0.77	0.77
	Autophagy (G, CDKN2A)	0.75	0.76
	Myogenesis (H)	0.75	0.76
	Urogenital system development (G, PTEN)	0.81	0.81
	Muscle structure development (G, COL6A3)	0.80	0.80	Zinn et al. (2011)
	Response to growth factor (G, EGFR, POSTN)	0.76	0.81	Zinn et al. (2011)
Vasculature	Heme metabolism (H)	0.77	0.73
Differentiation	Central nervous sys. neuron differentiation (G, PTEN)	0.79	0.81
	Cell differentiation (G, MET)	0.79	0.81
	Stem cell differentiation (G, CDK6)	0.80	0.80
Immune system	Reg. of cell activation (G, CDKN2A)	0.83	0.82
	Neg. reg. of immune system (G, CDKN2A, CXCL12)	0.82	0.81	Zinn et al. (2011)
	Immune effector process (G, PIK3CA)	0.80	0.81
Other	Glycolysis (H)	0.76	0.70
nCET
Cell cycle	Mitotic spindle (H)	0.78	0.70
	DNA repair (H)	0.77	0.66
	G2M checkpoint (H)	0.72	0.63
	Reg. of mitotic cell cycle (G, TP53)	0.78	0.71
Growth/death	p53 pathway (H)	0.76	0.65
	Urogenital and vasculature development (G, PTEN)	0.81^c	0.74^c
	Neg. reg. of cell cycle (G, TP53)	0.80	0.74
	Reproductive system development (G, EGFR)	0.80	0.72
UV	UV response down (H)	0.78	0.59
UV	Response to radiation (G, TP53)	0.83	0.73
Other	Glycerphospholip metabolism process (G, EGFR)	0.75	0.74
Other	Small molecule catabolic process (G, PTEN)	0.78	0.73
Necrosis
Vasculature	Heme metabolism (H)	0.72	0.61
Growth/death	Apoptosis (H)	0.71	0.58
	Apoptotic signaling pathway (G, IL4, TP53)	0.72	0.63	Gevaert et al. (2014)
	Related to TP53	0.76^c	0.66^c
	Gland development (G, EGFR)	0.76	0.65
Immune system	IL6/JAK/STAT3 signaling (H)	0.67	0.56
	Leukocyte cell adhesion (G, IL4, ITGA5)	0.76	0.59	Gevaert et al. (2014); Jamshidi et al. (2014)
	Reg. of leukocyte proliferation (G, CDKN2A)	0.77	0.61	Gutman et al. (2013)
Others	Xenobiotic metabolism (H)	0.76	0.65
	Related to PTEN	0.76^c	0.65^c
	Reg. of homeostatic process (G, NF1)	0.78	0.65
	Glycolysis (H)	0.76	0.56
Focal
Growth/death	Reg. of anatomical structure size (G, PTEN)	0.96	0.88
	Response to growth factor (G, EGFR)	0.92	0.83
Transport	Secretion by cell (G, NF1)	0.95	0.88
	Neg. reg. of transport (G, PTEN)	0.96	0.87
	Reg. of cytoplasmic transport (G, TP53)	0.95	0.85
	Monovalent inorganic cation transport (G, PARK2)	0.95	0.81
Response to	Steroid hormone, lipid and organic cyclic compound (G, RB1)	0.95^c	0.84^c
Vasculature	Vasculature development (G, PTEN)	0.93	0.84
Vasculature	Muscle and circulatory system process (G, PIK3CA)	0.94^c	0.83^c
Oxygen	Hypoxia (H)	0.85	0.61
Others	Genes down-regulated by KRAS (H)	0.88	0.64
	Protein heterodimerization activity (G, TP53)	0.97	0.85
	Neg. reg. of intracellular signaling transduction (G, PTEN)	0.96	0.84
	Synaptic signaling (G, PTEN)	0.92	0.82
Infiltrative
Oxygen	Reactive oxygen species pathway (H)	0.71	0.50
Oxygen	Response to oxygen levels (G, TP53)	0.67	0.60
Transport	Neg. reg. of transport (G, PTEN, NFKBIA)	0.74	0.64	Colen et al. (2014)
Healing	Wound healing (G, NF1)	0.80	0.64
Healing	Hemostasis (G, PIK3CA)	0.78	0.59
Growth/death	Developmental growth (G, PTEN)	0.74	0.62
Growth/death	Spinal cord development (G, NF1)	0.66	0.60
Response to	Response to drug (G, MDM2, MYC)	0.75	0.60
Response to	Response to inorganic substance (G, PTEN)	0.73	0.61	Colen et al. (2014)
Others	DNA repair (H)	0.70	0.58
	Ligase activity (G, MDM2)	0.75	0.64
	Ubiquitin-like protein transferase activity (G, MDM2)	0.70	0.59
	Ubiquitin-like protein ligase binding (G, NFKBIA)	0.67	0.57	Colen et al. (2014)
	Related to protein and transcription factor complex (G, TP53)	0.75^c	0.62^c
	WNT signaling pathway (G, PTEN, MYC)	0.73	0.62	Colen et al. (2014)

Note: The top five gene sets ranked by AUC or AP and compared against gene sets related to prior GBM work in gene abnormalities (McLendon et al., 2008; Parsons et al., 2008) or radiogenomics.

MSigDB: H, hallmark; G, Gene Ontology; C, canonical.

Gene sets queried in MSigDB using keyword(s) reported in Colen et al. (2014), Diehn et al. (2008), Gevaert et al. (2014), Gutman et al. (2013), Jamshidi et al. (2014) and Zinn et al. (2011).

Averaged.

neg., negative; reg., regulation; sys., system.