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Deciphering the molecular landscape of ionising radiation-induced eye damage with the help of genomic data mining

Katarina Baralić
Katarina Baralić
, 
Predrag Božović
Predrag Božović
 et 
Danijela Đukić-Ćosić
Danijela Đukić-Ćosić
   | 29 juin 2024
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Article Category: Original article
Publié en ligne: 29 juin 2024
Pages: 91 - 101
Reçu: 01 janv. 2024
Accepté: 01 mai 2024
DOI: https://doi.org/10.2478/aiht-2024-75-3817
Mots clés
© 2024 Katarina Baralić et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.

Figure 1

Detailed step-by-step diagram showing different phases of gene database analysis applied to investigate the relationship between the ionising radiation and eye injury
Detailed step-by-step diagram showing different phases of gene database analysis applied to investigate the relationship between the ionising radiation and eye injury

Figure 2

GeneMANIA network of genes associated with eye injury caused by ionising radiation (black) together with the 20 related genes (grey). Interaction type: 100 % physical interactions (GeneMANIA; https://apps.cytoscape.org/apps/genemania)
GeneMANIA network of genes associated with eye injury caused by ionising radiation (black) together with the 20 related genes (grey). Interaction type: 100 % physical interactions (GeneMANIA; https://apps.cytoscape.org/apps/genemania)

Figure 3

Subnetwork of interconnected genes associated with eye injury caused by ionising radiation (yellow) obtained with MCODE algorithm (https://apps.cytoscape.org/apps/mcode): (A) all input genes (n=26); (B) highly interconnected genes
Subnetwork of interconnected genes associated with eye injury caused by ionising radiation (yellow) obtained with MCODE algorithm (https://apps.cytoscape.org/apps/mcode): (A) all input genes (n=26); (B) highly interconnected genes

Gene set linked to the eye injury caused by ionising radiation based on CTD and GeneMANIA analysis (http://ctdbase.org/; https://apps.cytoscape.org/apps/genemania)

Gene symbol Gene name Gene ID
ATM ATM serine/threonine kinase 472
CRYAB Crystallin alpha B 1410
SIRT1 Sirtuin 1 23411
TGFB1 Transforming growth factor beta 1 7040
TREX1 Three prime repair exonuclease 1 11277
YAP1 Yes1 associated transcriptional regulator 10413
TEAD2 TEA domain transcription factor 2 8463
RRP8 Ribosomal RNA processing 8 23378
CS Citrate synthase 1431
TIPARP TCDD inducible poly(ADP-ribose) polymerase 25976
CRYGC Crystallin gamma C 1420
HIC1 HIC ZBTB transcriptional repressor 1 3090
EEF1E1 Eukaryotic translation elongation factor 1 epsilon 1 9521
LTBP4 Latent transforming growth factor beta binding protein 4 8425
NBN Nibrin 4683
MSH2 MutS homolog 2 4436
WBP1 WW domain binding protein 1 23559
AMOTL1 Angiomotin like 1 154810
BMP3 Bone morphogenetic protein 3 651
LBH LBH regulator of WNT signaling pathway 81606
CRYGS Crystallin gamma S 1427
IFT20 Intraflagellar transport 20 90410
ITGB8 Integrin subunit beta 8 3696
FCN1 Ficolin 1 2219
CRYBB2 Crystallin beta B2 1415
ATR ATR serine/threonine kinase 545

Diseases and interacting genes associated with eye injury caused by radiation (CTD; http://ctdbase.org/)

Phenotype Disease Gene
Cellular response to gamma radiation Cataract ATM | CRYAB
Cellular response to ionising radiation Diabetic retinopathy SIRT1
Cellular response to ionising radiation Retinal diseases SIRT1
Cellular response to gamma radiation Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or impaired intellectual development YAP1
Cellular response to gamma radiation Cataract 16, multiple types CRYAB
Regulation of cellular response to gamma radiation Cataract ATM
Cellular response to gamma radiation Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related CRYAB
Cellular response to X-ray Cataract ATM
Cellular response to gamma radiation Alpha-B crystallinopathy CRYAB
Cellular response to ionising radiation Dry eye syndromes TGFB1
Cellular response to ionising radiation Cataract ATM
Cellular response to gamma radiation Vasculopathy, retinal, with cerebral leukodystrophy TREX1
Cellular response to ionising radiation Graves disease TGFB1

Top 15 gene ontology (molecular functions, biological processes) and molecular pathways associated with eye injury caused by ionising radiation (https://toppgene.cchmc.org)

ID Name p-value Input genes Annotated genes
Molecular functions GO:0005212 structural constituent of eye lens 2.806E-8 4 25
GO:0032405 MutLalpha complex binding 6.840E-8 3 7
GO:0032404 mismatch repair complex binding 3.214E-7 3 11
GO:0032407 MutSalpha complex binding 3.412E-5 2 7
GO:0044877 protein-containing complex binding 2.123E-4 9 1726
GO:0003950 NAD+ ADP-ribosyltransferase activity 6.938E-4 2 30
GO:0047485 protein N-terminus binding 7.323E-4 3 137
GO:0050699 WW domain binding 8.919E-4 2 34
GO:0004108 citrate (Si)-synthase activity 1.304E-3 1 1
GO:0160011 NAD-dependent protein decrotonylase activity 1.304E-3 1 1
GO:0160012 NAD-dependent histone decrotonylase activity 1.304E-3 1 1
GO:0036440 citrate synthase activity 1.304E-3 1 1
GO:0016763 pentosyltransferase activity 2.491E-3 2 57
GO:0106231 protein-propionyllysine depropionylase activity 2.603E-3 1 2
GO:0032129 histone deacetylase activity (H3-K9 specific) 2.603E-3 1 2
Biological processes GO:0071479 cellular response to ionising radiation 1.415E-11 7 90
GO:0042770 signal transduction in response to DNA damage 8.815E-11 8 200
GO:0010212 response to ionising radiation 9.545E-11 8 202
GO:0072331 signal transduction by p53 class mediator 9.545E-11 8 202
GO:0071480 cellular response to gamma radiation 5.615E-10 5 34
GO:0030330 DNA damage response, signal transduction by p53 class mediator 7.424E-10 6 83
GO:0043516 regulation of DNA damage response, signal transduction by p53 class mediator 2.173E-9 5 44
GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator 4.584E-9 4 17
GO:0097190 apoptotic signaling pathway 7.241E-9 10 715
GO:0071478 cellular response to radiation 8.951E-9 7 225
GO:0010332 response to gamma radiation 4.104E-8 5 78
GO:0009314 response to radiation 5.117E-8 9 646
GO:0045786 negative regulation of cell cycle 8.888E-8 8 483
GO:1901798 positive regulation of signal transduction by p53 class mediator 9.931E-8 4 35
GO:0097193 intrinsic apoptotic signalling pathway 2.361E-7 7 363
Cellular components GO:0061773 eNoSc complex 4.112E-6 2 3
GO:0140552 TEAD-YAP complex 4.112E-6 2 3
GO:0033553 rDNA heterochromatin 8.218E-6 2 4
GO:0000781 chromosome, telomeric region 4.993E-5 4 173
GO:0005677 chromatin silencing complex 1.237E-4 2 14
GO:0140513 nuclear protein-containing complex 1.424E-4 8 1386
GO:0016605 PML body 4.055E-4 3 122
GO:0098687 chromosomal region 1.439E-3 4 419
GO:0070310 ATR-ATRIP complex 2.389E-3 1 2
GO:0032301 MutSalpha complex 2.389E-3 1 2
GO:0034686 integrin alphav-beta8 complex 2.389E-3 1 2
GO:0032302 MutSbeta complex 2.389E-3 1 2
GO:0099126 transforming growth factor beta complex 3.582E-3 1 3
GO:1902636 kinociliary basal body 3.582E-3 1 3
GO:0005657 replication fork 3.703E-3 2 76
Molecular pathways M9703 role of BRCA1, BRCA2 and ATR in Cancer Susceptibility 3.010E-8 4 22
M39490 DNA IR-damage and cellular response via ATR 1.245E-7 5 81
M39598 DNA IR-double strand breaks and cellular response via ATM 1.358E-6 4 55
M648 cell Cycle: G1/S Check Point 1.012E-5 3 28
137959 BARD1 signalling events 1.128E-5 3 29
M258 BARD1 signalling events 1.128E-5 3 29
1270252 molecules associated with elastic fibres 1.384E-5 3 31
1309108 HDR through Single Strand Annealing (SSA) 2.580E-5 3 38
1309104 presynaptic phase of homologous DNA pairing and strand exchange 3.016E-5 3 40
M40049 DNA repair pathways, full network 3.166E-5 4 121
1309097 sensing of DNA Double Strand Breaks 3.389E-5 2 6
1270251 elastic fibre formation 3.497E-5 3 42
1309103 homologous DNA Pairing and Strand Exchange 3.756E-5 3 43
M39628 integrated cancer pathway 4.310E-5 3 45
M39518 ATM signalling in development and disease 4.606E-5 3 46

Gene ontology terms linked to the obtained MCODE network [Metascape software (https://metascape.org)]

GO Description Log10(P)
GO:0010212 response to ionising radiation −10.5
GO:0071479 cellular response to ionising radiation −10.4
GO:0071480 cellular response to gamma radiation −10.4
GO:0000077 DNA damage checkpoint signalling −12.3
GO:0031570 DNA integrity checkpoint signalling −12.2
GO:0042770 signal transduction in response to DNA damage −11.7

miRNAs linked to eye injury caused by ionising radiation (https://toppgene.cchmc.org)

ID Name pValue Input genes Annotated genes
hsa-miR-892b:mirSVR lowEffct hsa-miR-892b:mirSVR non-conserved low effect-0.1-0.5 2.811E-7 8 1596
hsa-miR-183:mirSVR highEffct hsa-miR-183:mirSVR conserved high effect-0.5 1.597E-6 6 853
hsa-miR-708:mirSVR lowEffct hsa-miR-708:mirSVR non-conserved low effect-0.1-0.5 1.629E-6 7 1376
hsa-miR-3688-3p 2.792E-6 6 940
hsa-miR-3118:mirSVR lowEffct hsa-miR-3118:mirSVR non-conserved low effect-0.1-0.5 4.640E-6 7 1613
hsa-miR-19a-3p 6.859E-6 6 1100
hsa-miR-19b-3p 7.002E-6 6 1104
hsa-miR-590-5p 1.105E-5 4 317
hsa-miR-3166:mirSVR lowEffct hsa-miR-3166:mirSVR non-conserved low effect-0.1-0.5 1.146E-5 7 1853
hsa-miR-589:mirSVR highEffct hsa-miR-589:mirSVR non-conserved high effect-0.5 1.182E-5 7 1862
hsa-miR-548ap-3p 1.281E-5 6 1228
hsa-miR-548t-3p 1.281E-5 6 1228
hsa-miR-548aa 1.281E-5 6 1228
hsa-miR-21-5p 1.455E-5 4 340
hsa-miR-19b:PITA hsa-miR-19b:PITA TOP 1.615E-5 5 741
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