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Table 6 TBI-I Gene interaction hierarchy (GIH)

From: Bilateral gene interaction hierarchy analysis of the cell death gene response emphasizes the significance of cell cycle genes following unilateral traumatic brain injury

Gene symbol

Entrez gene name

Fold change

Cellular compartment

Molecular type

Primary

    

 ATF3

activating transcription factor 3

12.027

Nucleus

transcription regulator

  CCND1

cyclin D1

2.152

Nucleus

transcription regulator

 CEBPB

CCAAT/enhancer binding protein (C/EBP), beta

3.366

Nucleus

transcription regulator

 CREB1

cAMP responsive element binding protein 1

2.666

Nucleus

transcription regulator

 CREBBP

CREB binding protein

2.421

Nucleus

transcription regulator

 MDM2

MDM2 proto-oncogene, E3 ubiquitin protein ligase

2.01

Nucleus

transcription regulator

 NFE2L2

nuclear factor, erythroid 2-like 2

2.452

Nucleus

transcription regulator

  SMARCA4

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4

2.521

Nucleus

transcription regulator

  STAT3

signal transducer and activator of transcription 3 (acute-phase response factor)

4.219

Nucleus

transcription regulator

 CDK1

cyclin-dependent kinase 1

2.105

Nucleus

kinase

  CSNK2A1

casein kinase 2, alpha 1 polypeptide

2.992

Cytoplasm

kinase

  EGFR

epidermal growth factor receptor

6.773

Plasma Membrane

kinase

  GSK3B

glycogen synthase kinase 3 beta

−2.733

Nucleus

kinase

  CD44

CD44 molecule (Indian blood group)

15.558

Plasma Membrane

enzyme

 FN1

fibronectin 1

3.97

Extracellular Space

enzyme

 TRAF6

TNF receptor-associated factor 6, E3 ubiquitin protein ligase

2.163

Cytoplasm

enzyme

 CASP3

caspase 3, apoptosis-related cysteine peptidase

2.535

Cytoplasm

peptidase

 ELAVL1

ELAV like RNA binding protein 1

3.275

Cytoplasm

other

Secondary

    

  CEBPD

CCAAT/enhancer binding protein (C/EBP), delta

11.271

Nucleus

transcription regulator

 CREM

cAMP responsive element modulator

2.165

Nucleus

transcription regulator

 EGR2

early growth response 2

2.271

Nucleus

transcription regulator

 FOSL1

FOS-like antigen 1

5.875

Nucleus

transcription regulator

 KLF4

Kruppel-like factor 4 (gut)

2.057

Nucleus

transcription regulator

 MITF

microphthalmia-associated transcription factor

4.755

Nucleus

transcription regulator

  TCF4

transcription factor 4

−2.216

Nucleus

transcription regulator

 HSPA1A/HSPA1B

heat shock 70 kDa protein 1A

3.137

Cytoplasm

enzyme

 MCM2

minichromosome maintenance complex component 2

2.57

Nucleus

enzyme

 PTGS2

prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase)

3.106

Cytoplasm

enzyme

 IL1B

interleukin 1, beta

5.166

Extracellular Space

cytokine

  SPP1

secreted phosphoprotein 1

37.905

Extracellular Space

cytokine

 CDKN1B

cyclin-dependent kinase inhibitor 1B (p27, Kip1)

3.732

Nucleus

kinase

 IKBKB

inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta

2.127

Cytoplasm

kinase

 KPNB1

karyopherin (importin) beta 1

3.173

Nucleus

transporter

 MCL1

myeloid cell leukemia 1

3.25

Cytoplasm

transporter

  THRA

thyroid hormone receptor, alpha

−2.799

Nucleus

ligand-dependent nuclear receptor

 CASP7

caspase 7, apoptosis-related cysteine peptidase

2.579

Cytoplasm

peptidase

 BAG3

BCL2-associated athanogene 3

4.045

Cytoplasm

other

 CCNA2

cyclin A2

2.633

Nucleus

other

 GFAP

glial fibrillary acidic protein

3.011

Cytoplasm

other

 HSPA9

heat shock 70 kDa protein 9 (mortalin)

2.666

Cytoplasm

other

  HSPB1

heat shock 27 kDa protein 1

46.922

Cytoplasm

other

 SNCA

synuclein, alpha (non A4 component of amyloid precursor)

−2.169

Cytoplasm

other

Peripheral

    

 ACSL5

acyl-CoA synthetase long-chain family member 5

−2.361

Cytoplasm

enzyme

 ANXA1

annexin A1

3.535

Plasma Membrane

enzyme

 CHSY1

chondroitin sulfate synthase 1

2.873

Cytoplasm

enzyme

  CP

ceruloplasmin (ferroxidase)

27.838

Extracellular Space

enzyme

  EHD4

EH-domain containing 4

2.361

Plasma Membrane

enzyme

 GCLM

glutamate-cysteine ligase, modifier subunit

2.019

Cytoplasm

enzyme

 HMOX1

heme oxygenase (decycling) 1

9.778

Cytoplasm

enzyme

 MCM8

minichromosome maintenance complex component 8

2.027

Nucleus

enzyme

  MX1

MX dynamin-like GTPase 1

28.177

Cytoplasm

enzyme

  PDE4B

phosphodiesterase 4B, cAMP-specific

5.602

Cytoplasm

enzyme

 RAB35

RAB35, member RAS oncogene family

2.086

Cytoplasm

enzyme

 RRM2

ribonucleotide reductase M2

3.34

Nucleus

enzyme

  SDC1

syndecan 1

13.681

Plasma Membrane

enzyme

  SETD8

SET domain containing (lysine methyltransferase) 8

2.029

Nucleus

enzyme

 SGPL1

sphingosine-1-phosphate lyase 1

3.108

Cytoplasm

enzyme

  SRXN1

sulfiredoxin 1

6.306

Cytoplasm

enzyme

 TGM2

transglutaminase 2

3.574

Cytoplasm

enzyme

  TOP2A

topoisomerase (DNA) II alpha 170 kDa

2.26

Nucleus

enzyme

 BCL11A

B-cell CLL/lymphoma 11A (zinc finger protein)

−2.38

Nucleus

transcription regulator

  BTG2

BTG family, member 2

−2.22

Nucleus

transcription regulator

  CCAR1

cell division cycle and apoptosis regulator 1

−2.943

Nucleus

transcription regulator

 CSRNP1

cysteine-serine-rich nuclear protein 1

2.821

Nucleus

transcription regulator

  DEK

DEK proto-oncogene

−3.006

Nucleus

transcription regulator

  DNAJB6

DnaJ (Hsp40) homolog, subfamily B, member 6

−4.383

Nucleus

transcription regulator

 ETV5

ets variant 5

−2.163

Nucleus

transcription regulator

  KLF13

Kruppel-like factor 13

−2.006

Nucleus

transcription regulator

  KLF6

Kruppel-like factor 6

6.003

Nucleus

transcription regulator

  NAA15

N(alpha)-acetyltransferase 15, NatA auxiliary subunit

3.605

Nucleus

transcription regulator

  NFIX

nuclear factor I/X (CCAAT-binding transcription factor)

−2.548

Nucleus

transcription regulator

 NFKB2

nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)

2.768

Nucleus

transcription regulator

  PA2G4

proliferation-associated 2G4, 38 kDa

−2.702

Nucleus

transcription regulator

 PRDM2

PR domain containing 2, with ZNF domain

3.677

Nucleus

transcription regulator

  TBL1XR1

transducin (beta)-like 1 X-linked receptor 1

2.587

Nucleus

transcription regulator

 TCEB3

transcription elongation factor B (SIII), polypeptide 3 (110 kDa, elongin A)

3.053

Nucleus

transcription regulator

 CAMK1G

calcium/calmodulin-dependent protein kinase IG

−2.271

Cytoplasm

kinase

  CAMK2N1

calcium/calmodulin-dependent protein kinase II inhibitor 1

−11.813

Plasma Membrane

kinase

  CARD11

caspase recruitment domain family, member 11

7.343

Cytoplasm

kinase

  CDK11A

cyclin-dependent kinase 11A

−4.29

Nucleus

kinase

 FGR

FGR proto-oncogene, Src family tyrosine kinase

3.915

Nucleus

kinase

 HCK

HCK proto-oncogene, Src family tyrosine kinase

3.887

Cytoplasm

kinase

 HSPB8

heat shock 22 kDa protein 8

4.112

Cytoplasm

kinase

 LATS1

large tumor suppressor kinase 1

2.003

Nucleus

kinase

 MAP4K4

mitogen-activated protein kinase kinase kinase kinase 4

2.258

Cytoplasm

kinase

 NEK6

NIMA-related kinase 6

2.322

Nucleus

kinase

  SRPK2

SRSF protein kinase 2

−5.614

Nucleus

kinase

 TJP2

tight junction protein 2

2.552

Plasma Membrane

kinase

 Ccl2

chemokine (C-C motif) ligand 2

195.455

Extracellular Space

cytokine

 CCL3L3

chemokine (C-C motif) ligand 3-like 3

5.269

Extracellular Space

cytokine

 CCL4

chemokine (C-C motif) ligand 4

2.162

Extracellular Space

cytokine

 Ccl6

chemokine (C-C motif) ligand 6

10.291

Extracellular Space

cytokine

 Ccl7

chemokine (C-C motif) ligand 7

124.78

Extracellular Space

cytokine

 CXCL3

chemokine (C-X-C motif) ligand 3

13.211

Extracellular Space

cytokine

 Cxcl9

chemokine (C-X-C motif) ligand 9

2.846

Extracellular Space

cytokine

  TIMP1

TIMP metallopeptidase inhibitor 1

38.486

Extracellular Space

cytokine

 IL6R

interleukin 6 receptor

2.315

Plasma Membrane

transmembrane receptor

  IL6ST

interleukin 6 signal transducer

2.307

Plasma Membrane

transmembrane receptor

 ITGB2

integrin, beta 2 (complement component 3 receptor 3 and 4 subunit)

2.675

Plasma Membrane

transmembrane receptor

 TLR4

toll-like receptor 4

2.699

Plasma Membrane

transmembrane receptor

 TNFRSF1A

tumor necrosis factor receptor superfamily, member 1A

3.555

Plasma Membrane

transmembrane receptor

 UNC5B

unc-5 homolog B (C. elegans)

2.067

Plasma Membrane

transmembrane receptor

 ALB

albumin

−3.125

Extracellular Space

transporter

  LCN2

lipocalin 2

71.824

Extracellular Space

transporter

  RASA1

RAS p21 protein activator (GTPase activating protein) 1

2.392

Cytoplasm

transporter

  TPR

translocated promoter region, nuclear basket protein

2.212

Nucleus

transporter

  FGL2

fibrinogen-like 2

16.793

Extracellular Space

peptidase

 SENP2

SUMO1/sentrin/SMT3 specific peptidase 2

2.051

Nucleus

peptidase

 DUSP5

dual specificity phosphatase 5

3.285

Nucleus

phosphatase

  PTPRF

protein tyrosine phosphatase, receptor type, F

−6.365

Plasma Membrane

phosphatase

  EIF3C

eukaryotic translation initiation factor 3, subunit C

−4.369

Other

translation regulator

  EIF5B

eukaryotic translation initiation factor 5B

−3.044

Cytoplasm

translation regulator

 FGF2

fibroblast growth factor 2 (basic)

2.387

Extracellular Space

growth factor

  KCND2

potassium voltage-gated channel, Shal-related subfamily, member 2

−2.792

Plasma Membrane

ion channel

  AHI1

Abelson helper integration site 1

2.243

Cytoplasm

other

 BCL2A1

BCL2-related protein A1

3.055

Cytoplasm

other

 CALB1

calbindin 1, 28 kDa

−2.091

Cytoplasm

other

  CD68

CD68 molecule

4.365

Plasma Membrane

other

 CDCA7L

cell division cycle associated 7-like

2.648

Nucleus

other

  CDT1

chromatin licensing and DNA replication factor 1

3.098

Nucleus

other

  CISD2

CDGSH iron sulfur domain 2

−7.833

Cytoplasm

other

  CMIP

c-Maf inducing protein

−3.778

Cytoplasm

other

 DAB2

Dab, mitogen-responsive phosphoprotein, homolog 2 (Drosophila)

3.053

Plasma Membrane

other

 DES

desmin

2.857

Cytoplasm

other

 DNAJB9

DnaJ (Hsp40) homolog, subfamily B, member 9

2.128

Nucleus

other

 FLNA

filamin A, alpha

3.45

Cytoplasm

other

  GADD45G

growth arrest and DNA-damage-inducible, gamma

3.191

Nucleus

other

  HLA-A

major histocompatibility complex, class I, A

9.296

Plasma Membrane

other

 HSPA2

heat shock 70 kDa protein 2

3.51

Cytoplasm

other

  LCP1

lymphocyte cytosolic protein 1 (L-plastin)

6.082

Cytoplasm

other

  LSP1

lymphocyte-specific protein 1

11.716

Cytoplasm

other

 MMS22L

MMS22-like, DNA repair protein

2.918

Nucleus

other

 MSI2

musashi RNA-binding protein 2

2.288

Cytoplasm

other

 PDLIM7

PDZ and LIM domain 7 (enigma)

4.695

Cytoplasm

other

  PHLDA1

pleckstrin homology-like domain, family A, member 1

5.129

Cytoplasm

other

  PMEPA1

prostate transmembrane protein, androgen induced 1

2.682

Plasma Membrane

other

  PSIP1

PC4 and SFRS1 interacting protein 1

−2.663

Nucleus

other

  RDX

radixin

4.828

Cytoplasm

other

  SERPINA3

serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3

58.488

Extracellular Space

other

 SPIN1

spindlin 1

2.178

Nucleus

other

 SUDS3

suppressor of defective silencing 3 homolog (S. cerevisiae)

2.228

Nucleus

other

 TAGLN2

transgelin 2

3.891

Cytoplasm

other

  THOC2

THO complex 2

2.119

Nucleus

other

 TMEM109

transmembrane protein 109

2.106

Cytoplasm

other

 TMEM123

transmembrane protein 123

2.348

Plasma Membrane

other

Orphan

    

  CYP1B1

cytochrome P450, family 1, subfamily B, polypeptide 1

10.998

Cytoplasm

enzyme

  KIF3A

kinesin family member 3A

−5.083

Cytoplasm

enzyme

 PTGR1

prostaglandin reductase 1

2.258

Cytoplasm

enzyme

  RND3

Rho family GTPase 3

2.864

Cytoplasm

enzyme

 WFS1

Wolfram syndrome 1 (wolframin)

2.083

Cytoplasm

enzyme

 ITPR2

inositol 1,4,5-trisphosphate receptor, type 2

2.489

Cytoplasm

ion channel

  KCNN4

potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4

3.088

Plasma Membrane

ion channel

  ATRX

alpha thalassemia/mental retardation syndrome X-linked

2.091

Nucleus

transcription regulator

 RAI14

retinoic acid induced 14

3.284

Nucleus

transcription regulator

 CX3CL1

chemokine (C-X3-C motif) ligand 1

−2.044

Extracellular Space

cytokine

 PTGER3

prostaglandin E receptor 3 (subtype EP3)

2.425

Plasma Membrane

G-protein coupled receptor

 PI4K2A

phosphatidylinositol 4-kinase type 2 alpha

2.96

Cytoplasm

kinase

 CD36

CD36 molecule (thrombospondin receptor)

5.08

Plasma Membrane

transmembrane receptor

 ARL11

ADP-ribosylation factor-like 11

3.143

Other

other

  Brd4

bromodomain containing 4

−3.528

Nucleus

other

 CLN5

ceroid-lipofuscinosis, neuronal 5

2.041

Cytoplasm

other

  Ctdspl

CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase-like

−7.271

Cytoplasm

other

  KIFAP3

kinesin-associated protein 3

−2.281

Cytoplasm

other

  Nos1ap

nitric oxide synthase 1 (neuronal) adaptor protein

−2.698

Other

other

 PCDH15

protocadherin-related 15

2.147

Plasma Membrane

other

  RASSF4

Ras association (RalGDS/AF-6) domain family member 4

4.289

Other

other

  Rbm25

RNA binding motif protein 25

−5.547

Nucleus

other

  Slpi

secretory leukocyte peptidase inhibitor

82.908

Cytoplasm

other

  Tpm3

tropomyosin 3

2.592

Cytoplasm

other

  TRIM54

tripartite motif containing 54

−4.426

Cytoplasm

other

  1. Primary: >14 connections in GOI network (see text); Secondary: 8–14 connections in GOI network; Peripheral: <8 connections in GOI network; Orphan: No connections in GOI network; Italics= > Gene changes on both sides of the brain