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

Katarina Baralić; Predrag Božović; Danijela Đukić-Ćosić

doi:10.2478/aiht-2024-75-3817

Figures & Tables

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

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)

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

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

Figures & Tables

Figure 1

Figure 2

Figure 3

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)

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

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

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

miRNAs linked to eye injury caused by ionising radiation (https://toppgene_cchmc_org)

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