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: COX5B

Gene summary for COX5B

Gene summary.

Gene information	Species	Human
	Gene symbol	COX5B
	Gene ID	1329
	Gene name	cytochrome c oxidase subunit 5B
	Gene Alias	COXVB
	Cytomap	2q11.2
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	P10606

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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
1329	COX5B	GSM4909281	Human	Breast	IDC	5.52e-04	2.60e-01	0.21
1329	COX5B	GSM4909282	Human	Breast	IDC	2.69e-16	4.10e-01	-0.0288
1329	COX5B	GSM4909285	Human	Breast	IDC	1.74e-15	4.09e-01	0.21
1329	COX5B	GSM4909287	Human	Breast	IDC	8.28e-10	1.74e-01	0.2057
1329	COX5B	GSM4909288	Human	Breast	IDC	7.60e-07	1.67e-01	0.0988
1329	COX5B	GSM4909289	Human	Breast	IDC	1.11e-03	3.53e-01	0.1064
1329	COX5B	GSM4909290	Human	Breast	IDC	6.46e-09	3.10e-01	0.2096
1329	COX5B	GSM4909291	Human	Breast	IDC	1.77e-20	4.65e-01	0.1753
1329	COX5B	GSM4909293	Human	Breast	IDC	5.23e-05	2.28e-01	0.1581
1329	COX5B	GSM4909294	Human	Breast	IDC	9.43e-33	2.05e-01	0.2022
1329	COX5B	GSM4909296	Human	Breast	IDC	2.42e-21	1.44e-01	0.1524
1329	COX5B	GSM4909297	Human	Breast	IDC	6.26e-28	-1.34e-01	0.1517
1329	COX5B	GSM4909299	Human	Breast	IDC	1.28e-03	2.46e-01	0.035
1329	COX5B	GSM4909301	Human	Breast	IDC	4.55e-35	5.06e-01	0.1577
1329	COX5B	GSM4909302	Human	Breast	IDC	3.46e-05	7.18e-02	0.1545
1329	COX5B	GSM4909306	Human	Breast	IDC	3.21e-08	3.24e-01	0.1564
1329	COX5B	GSM4909307	Human	Breast	IDC	8.98e-04	2.18e-01	0.1569
1329	COX5B	GSM4909308	Human	Breast	IDC	6.35e-05	2.29e-01	0.158
1329	COX5B	GSM4909309	Human	Breast	IDC	1.63e-09	1.16e-01	0.0483
1329	COX5B	GSM4909311	Human	Breast	IDC	2.35e-57	-4.91e-02	0.1534

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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
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:00061237	Liver	Cyst	mitochondrial electron transport, cytochrome c to oxygen	5/496	21/18723	1.83e-04	7.05e-03	5
GO:002290018	Oral cavity	OSCC	electron transport chain	126/7305	175/18723	6.65e-19	8.42e-17	126
GO:000609118	Oral cavity	OSCC	generation of precursor metabolites and energy	286/7305	490/18723	1.45e-18	1.71e-16	286
GO:000906018	Oral cavity	OSCC	aerobic respiration	133/7305	189/18723	1.79e-18	2.02e-16	133
GO:004533318	Oral cavity	OSCC	cellular respiration	153/7305	230/18723	2.07e-17	1.87e-15	153
GO:004277318	Oral cavity	OSCC	ATP synthesis coupled electron transport	75/7305	95/18723	1.95e-15	1.33e-13	75
GO:004277518	Oral cavity	OSCC	mitochondrial ATP synthesis coupled electron transport	75/7305	95/18723	1.95e-15	1.33e-13	75
GO:002290418	Oral cavity	OSCC	respiratory electron transport chain	86/7305	114/18723	2.43e-15	1.63e-13	86
GO:001598018	Oral cavity	OSCC	energy derivation by oxidation of organic compounds	190/7305	318/18723	4.10e-14	2.26e-12	190
GO:001964618	Oral cavity	OSCC	aerobic electron transport chain	68/7305	87/18723	9.88e-14	5.17e-12	68
GO:004603420	Oral cavity	OSCC	ATP metabolic process	166/7305	277/18723	1.16e-12	5.12e-11	166
GO:000611919	Oral cavity	OSCC	oxidative phosphorylation	96/7305	141/18723	2.33e-12	9.75e-11	96
GO:002290019	Oral cavity	LP	electron transport chain	108/4623	175/18723	2.21e-25	9.90e-23	108
GO:000906019	Oral cavity	LP	aerobic respiration	111/4623	189/18723	1.68e-23	5.85e-21	111
GO:004277319	Oral cavity	LP	ATP synthesis coupled electron transport	69/4623	95/18723	9.69e-23	3.04e-20	69
GO:004277519	Oral cavity	LP	mitochondrial ATP synthesis coupled electron transport	69/4623	95/18723	9.69e-23	3.04e-20	69
GO:004533319	Oral cavity	LP	cellular respiration	124/4623	230/18723	1.35e-21	3.38e-19	124
GO:000609119	Oral cavity	LP	generation of precursor metabolites and energy	214/4623	490/18723	1.12e-20	2.60e-18	214
GO:002290419	Oral cavity	LP	respiratory electron transport chain	75/4623	114/18723	1.92e-20	4.14e-18	75
GO:001964619	Oral cavity	LP	aerobic electron transport chain	62/4623	87/18723	7.13e-20	1.49e-17	62

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501218	Breast	Precancer	Parkinson disease	99/684	266/8465	3.58e-42	5.65e-40	4.33e-40	99
hsa0502016	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0501616	Breast	Precancer	Huntington disease	98/684	306/8465	2.85e-35	2.25e-33	1.72e-33	98
hsa0019016	Breast	Precancer	Oxidative phosphorylation	59/684	134/8465	6.15e-30	3.24e-28	2.48e-28	59
hsa0501016	Breast	Precancer	Alzheimer disease	103/684	384/8465	1.03e-29	4.66e-28	3.57e-28	103
hsa0501416	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0502216	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0520818	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68
hsa0471418	Breast	Precancer	Thermogenesis	68/684	232/8465	4.40e-22	1.26e-20	9.69e-21	68
hsa0541518	Breast	Precancer	Diabetic cardiomyopathy	63/684	203/8465	5.63e-22	1.48e-20	1.14e-20	63
hsa0493216	Breast	Precancer	Non-alcoholic fatty liver disease	48/684	155/8465	6.16e-17	1.50e-15	1.15e-15	48
hsa0426016	Breast	Precancer	Cardiac muscle contraction	22/684	87/8465	9.72e-07	1.62e-05	1.24e-05	22
hsa0501219	Breast	Precancer	Parkinson disease	99/684	266/8465	3.58e-42	5.65e-40	4.33e-40	99
hsa0502017	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0501617	Breast	Precancer	Huntington disease	98/684	306/8465	2.85e-35	2.25e-33	1.72e-33	98
hsa0019017	Breast	Precancer	Oxidative phosphorylation	59/684	134/8465	6.15e-30	3.24e-28	2.48e-28	59
hsa0501017	Breast	Precancer	Alzheimer disease	103/684	384/8465	1.03e-29	4.66e-28	3.57e-28	103
hsa0501417	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0502217	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0520819	Breast	Precancer	Chemical carcinogenesis - reactive oxygen species	68/684	223/8465	3.61e-23	1.14e-21	8.73e-22	68

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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

COX5B

SNV

Missense_Mutation

rs746587601

c.335N>A

p.Arg112Gln

p.R112Q

P10606

protein_coding

tolerated(0.07)

benign(0.319)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

COX5B

insertion

Nonsense_Mutation

novel

c.169_170insAAAACTTTATATCTAAACTTACCAACT

p.Lys57_Gly58insAsnPheIleSerLysLeuThrAsnTer

p.K57_G58insNFISKLTN*

P10606

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

COX5B

SNV

Missense_Mutation

c.182N>A

p.Pro61Gln

p.P61Q

P10606

protein_coding

deleterious(0.02)

possibly_damaging(0.725)

TCGA-AZ-6598-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

COX5B

SNV

Missense_Mutation

rs142213285

c.344N>A

p.Arg115His

p.R115H

P10606

protein_coding

deleterious(0.03)

benign(0.003)

TCGA-D5-6540-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

COX5B

SNV

Missense_Mutation

novel

c.38N>T

p.Ala13Val

p.A13V

P10606

protein_coding

tolerated(0.11)

benign(0.051)

TCGA-AJ-A3BH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

COX5B

SNV

Missense_Mutation

novel

c.147N>C

p.Arg49Ser

p.R49S

P10606

protein_coding

deleterious(0.02)

probably_damaging(0.909)

TCGA-AX-A2IN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

COX5B

SNV

Missense_Mutation

c.218N>T

p.Thr73Ile

p.T73I

P10606

protein_coding

deleterious(0.01)

probably_damaging(0.98)

TCGA-B5-A0JN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

COX5B

SNV

Missense_Mutation

novel

c.54N>T

p.Arg18Ser

p.R18S

P10606

protein_coding

tolerated(0.06)

benign(0.018)

TCGA-EO-A22T-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

COX5B

SNV

Missense_Mutation

novel

c.293N>T

p.Thr98Ile

p.T98I

P10606

protein_coding

deleterious(0.01)

benign(0.309)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

COX5B

SNV

Missense_Mutation

novel

c.217A>T

p.Thr73Ser

p.T73S

P10606

protein_coding

tolerated(0.12)

benign(0.338)

TCGA-05-4398-01

Lung

lung adenocarcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

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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

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