Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: CYBA

Gene summary for CYBA

Gene summary.

Gene information	Species	Human
	Gene symbol	CYBA
	Gene ID	1535
	Gene name	cytochrome b-245 alpha chain
	Gene Alias	CGD4
	Cytomap	16q24.2
	Gene Type	protein-coding
	GO ID	GO:0001101
	UniProtAcc	B4DT46

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
1535	CYBA	GSM4909281	Human	Breast	IDC	5.10e-03	1.87e-01	0.21
1535	CYBA	GSM4909285	Human	Breast	IDC	1.04e-07	4.01e-02	0.21
1535	CYBA	GSM4909286	Human	Breast	IDC	3.91e-09	-2.31e-01	0.1081
1535	CYBA	GSM4909290	Human	Breast	IDC	3.89e-18	-6.32e-01	0.2096
1535	CYBA	GSM4909292	Human	Breast	IDC	7.11e-04	-7.13e-01	0.1236
1535	CYBA	GSM4909293	Human	Breast	IDC	4.64e-05	-5.09e-02	0.1581
1535	CYBA	GSM4909294	Human	Breast	IDC	1.45e-21	-6.28e-01	0.2022
1535	CYBA	GSM4909296	Human	Breast	IDC	1.26e-08	1.94e-01	0.1524
1535	CYBA	GSM4909297	Human	Breast	IDC	2.34e-29	-6.63e-01	0.1517
1535	CYBA	GSM4909298	Human	Breast	IDC	1.15e-06	-2.97e-01	0.1551
1535	CYBA	GSM4909302	Human	Breast	IDC	1.02e-14	-4.90e-01	0.1545
1535	CYBA	GSM4909304	Human	Breast	IDC	1.56e-07	4.09e-01	0.1636
1535	CYBA	GSM4909305	Human	Breast	IDC	4.62e-05	-3.25e-01	0.0436
1535	CYBA	GSM4909306	Human	Breast	IDC	2.45e-16	-5.51e-01	0.1564
1535	CYBA	GSM4909311	Human	Breast	IDC	3.91e-24	-5.82e-01	0.1534
1535	CYBA	GSM4909312	Human	Breast	IDC	5.42e-15	-4.99e-01	0.1552
1535	CYBA	GSM4909315	Human	Breast	IDC	5.00e-02	-2.91e-01	0.21
1535	CYBA	GSM4909317	Human	Breast	IDC	7.29e-08	5.15e-01	0.1355
1535	CYBA	GSM4909319	Human	Breast	IDC	7.70e-37	-6.94e-01	0.1563
1535	CYBA	GSM4909320	Human	Breast	IDC	2.31e-13	-7.04e-01	0.1575

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:007135618	Oral cavity	OSCC	cellular response to tumor necrosis factor	128/7305	229/18723	1.49e-07	2.49e-06	128
GO:200037716	Oral cavity	OSCC	regulation of reactive oxygen species metabolic process	92/7305	157/18723	4.96e-07	7.27e-06	92
GO:007147917	Oral cavity	OSCC	cellular response to ionizing radiation	49/7305	72/18723	5.59e-07	8.13e-06	49
GO:007137510	Oral cavity	OSCC	cellular response to peptide hormone stimulus	153/7305	290/18723	1.23e-06	1.63e-05	153
GO:004343419	Oral cavity	OSCC	response to peptide hormone	208/7305	414/18723	1.83e-06	2.35e-05	208
GO:00712605	Oral cavity	OSCC	cellular response to mechanical stimulus	52/7305	81/18723	3.86e-06	4.55e-05	52
GO:00022214	Oral cavity	OSCC	pattern recognition receptor signaling pathway	95/7305	172/18723	1.11e-05	1.15e-04	95
GO:00303079	Oral cavity	OSCC	positive regulation of cell growth	92/7305	166/18723	1.27e-05	1.29e-04	92
GO:000961210	Oral cavity	OSCC	response to mechanical stimulus	115/7305	216/18723	1.43e-05	1.44e-04	115
GO:005067310	Oral cavity	OSCC	epithelial cell proliferation	212/7305	437/18723	2.82e-05	2.61e-04	212
GO:000941018	Oral cavity	OSCC	response to xenobiotic stimulus	222/7305	462/18723	4.00e-05	3.48e-04	222
GO:007259316	Oral cavity	OSCC	reactive oxygen species metabolic process	122/7305	239/18723	9.73e-05	7.34e-04	122
GO:000974320	Oral cavity	OSCC	response to carbohydrate	128/7305	253/18723	1.11e-04	8.16e-04	128
GO:00103326	Oral cavity	OSCC	response to gamma radiation	36/7305	56/18723	1.12e-04	8.24e-04	36
GO:00011019	Oral cavity	OSCC	response to acid chemical	74/7305	135/18723	1.38e-04	9.76e-04	74
GO:00321037	Oral cavity	OSCC	positive regulation of response to external stimulus	203/7305	427/18723	1.79e-04	1.22e-03	203
GO:009730519	Oral cavity	OSCC	response to alcohol	127/7305	253/18723	1.81e-04	1.24e-03	127
GO:003428420	Oral cavity	OSCC	response to monosaccharide	114/7305	225/18723	2.37e-04	1.54e-03	114
GO:00432006	Oral cavity	OSCC	response to amino acid	64/7305	116/18723	2.96e-04	1.86e-03	64
GO:00712304	Oral cavity	OSCC	cellular response to amino acid stimulus	42/7305	71/18723	4.59e-04	2.76e-03	42

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0502016	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0520818	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68
hsa0541518	Breast	Precancer	Diabetic cardiomyopathy	63/684	203/8465	5.63e-22	1.48e-20	1.14e-20	63
hsa0541818	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa0541718	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0414518	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0467018	Breast	Precancer	Leukocyte transendothelial migration	20/684	114/8465	7.26e-04	5.33e-03	4.09e-03	20
hsa0502017	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0520819	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68
hsa0541519	Breast	Precancer	Diabetic cardiomyopathy	63/684	203/8465	5.63e-22	1.48e-20	1.14e-20	63
hsa0541819	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa0541719	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0414519	Breast	Precancer	Phagosome	27/684	152/8465	7.37e-05	6.85e-04	5.25e-04	27
hsa0467019	Breast	Precancer	Leukocyte transendothelial migration	20/684	114/8465	7.26e-04	5.33e-03	4.09e-03	20
hsa0502023	Breast	IDC	Prion disease	102/867	273/8465	3.70e-34	4.01e-32	3.00e-32	102
hsa0520824	Breast	IDC	Chemical carcinogenesis - reactive oxygen species	71/867	223/8465	2.55e-19	7.53e-18	5.63e-18	71
hsa0541523	Breast	IDC	Diabetic cardiomyopathy	67/867	203/8465	3.17e-19	8.59e-18	6.43e-18	67
hsa0541824	Breast	IDC	Fluid shear stress and atherosclerosis	34/867	139/8465	9.41e-07	1.61e-05	1.20e-05	34
hsa0414522	Breast	IDC	Phagosome	34/867	152/8465	8.00e-06	9.99e-05	7.48e-05	34
hsa0541724	Breast	IDC	Lipid and atherosclerosis	35/867	215/8465	3.67e-03	2.29e-02	1.71e-02	35

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

CYBA

SNV

Missense_Mutation

novel

c.316G>C

p.Ala106Pro

p.A106P

P13498

protein_coding

tolerated(0.57)

probably_damaging(0.974)

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

CYBA

SNV

Missense_Mutation

rs201755210

c.293N>T

p.Ser98Leu

p.S98L

P13498

protein_coding

deleterious(0.05)

benign(0.137)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CYBA

SNV

Missense_Mutation

rs776963412

c.134N>T

p.Ala45Val

p.A45V

P13498

protein_coding

tolerated(0.22)

probably_damaging(0.996)

TCGA-AJ-A3OJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

CYBA

SNV

Missense_Mutation

rs776963412

c.134N>T

p.Ala45Val

p.A45V

P13498

protein_coding

tolerated(0.22)

probably_damaging(0.996)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CYBA

SNV

Missense_Mutation

rs776963412

c.134N>T

p.Ala45Val

p.A45V

P13498

protein_coding

tolerated(0.22)

probably_damaging(0.996)

TCGA-B5-A0JV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CYBA

SNV

Missense_Mutation

rs13306293

c.223N>A

p.Ala75Thr

p.A75T

P13498

protein_coding

tolerated(0.58)

benign(0.003)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CYBA

SNV

Missense_Mutation

rs179363892

c.268C>T

p.Arg90Trp

p.R90W

P13498

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CYBA

SNV

Missense_Mutation

novel

c.355G>A

p.Gly119Ser

p.G119S

P13498

protein_coding

tolerated(0.41)

benign(0.007)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

CYBA

SNV

Missense_Mutation

novel

c.200N>A

p.Arg67His

p.R67H

P13498

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-DD-AACF-01

Liver

liver hepatocellular carcinoma

Male

>=65

I/II

Unknown

CYBA

SNV

Missense_Mutation

rs755658845

c.163C>T

p.Pro55Ser

p.P55S

P13498

protein_coding

tolerated(0.1)

probably_damaging(0.999)

TCGA-56-8628-01

Lung

lung squamous cell carcinoma

Male

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
1535	CYBA	TRANSPORTER		simvastatin	SIMVASTATIN	15936011
1535	CYBA	TRANSPORTER		idarubicin	IDARUBICIN	19448608,28485375,16330681,25823784
1535	CYBA	TRANSPORTER		doxorubicin	DOXORUBICIN	19448608,28485375,21048526,16330681,25823784

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