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: NDUFV2

Gene summary for NDUFV2

Gene summary.

Gene information	Species	Human
	Gene symbol	NDUFV2
	Gene ID	4729
	Gene name	NADH:ubiquinone oxidoreductase core subunit V2
	Gene Alias	CI-24k
	Cytomap	18p11.22
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	P19404

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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
4729	NDUFV2	GSM4909281	Human	Breast	IDC	1.99e-03	-2.66e-01	0.21
4729	NDUFV2	GSM4909286	Human	Breast	IDC	7.41e-07	-1.77e-01	0.1081
4729	NDUFV2	GSM4909292	Human	Breast	IDC	3.90e-02	-5.98e-01	0.1236
4729	NDUFV2	GSM4909294	Human	Breast	IDC	9.86e-03	-8.33e-03	0.2022
4729	NDUFV2	GSM4909296	Human	Breast	IDC	4.37e-08	-1.01e-01	0.1524
4729	NDUFV2	GSM4909297	Human	Breast	IDC	3.56e-23	-3.74e-01	0.1517
4729	NDUFV2	GSM4909298	Human	Breast	IDC	1.43e-08	-3.40e-01	0.1551
4729	NDUFV2	GSM4909299	Human	Breast	IDC	6.95e-03	-2.54e-01	0.035
4729	NDUFV2	GSM4909301	Human	Breast	IDC	4.57e-05	-2.67e-01	0.1577
4729	NDUFV2	GSM4909307	Human	Breast	IDC	5.03e-09	-4.08e-01	0.1569
4729	NDUFV2	GSM4909309	Human	Breast	IDC	3.65e-06	-3.63e-01	0.0483
4729	NDUFV2	GSM4909311	Human	Breast	IDC	1.65e-51	-6.65e-01	0.1534
4729	NDUFV2	GSM4909312	Human	Breast	IDC	3.06e-24	-5.15e-01	0.1552
4729	NDUFV2	GSM4909313	Human	Breast	IDC	3.53e-07	-3.69e-01	0.0391
4729	NDUFV2	GSM4909319	Human	Breast	IDC	1.71e-52	-4.85e-01	0.1563
4729	NDUFV2	GSM4909320	Human	Breast	IDC	4.54e-15	-7.12e-01	0.1575
4729	NDUFV2	GSM4909321	Human	Breast	IDC	1.52e-12	-3.34e-01	0.1559
4729	NDUFV2	brca1	Human	Breast	Precancer	2.66e-04	3.32e-01	-0.0338
4729	NDUFV2	brca2	Human	Breast	Precancer	4.08e-10	4.38e-01	-0.024
4729	NDUFV2	brca3	Human	Breast	Precancer	2.45e-09	3.85e-01	-0.0263

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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
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:0006091111	Skin	cSCC	generation of precursor metabolites and energy	224/4864	490/18723	1.13e-21	2.21e-19	224
GO:002290026	Skin	cSCC	electron transport chain	104/4864	175/18723	7.28e-21	1.23e-18	104
GO:0006119112	Skin	cSCC	oxidative phosphorylation	89/4864	141/18723	1.56e-20	2.49e-18	89
GO:004277326	Skin	cSCC	ATP synthesis coupled electron transport	68/4864	95/18723	1.59e-20	2.49e-18	68
GO:004277526	Skin	cSCC	mitochondrial ATP synthesis coupled electron transport	68/4864	95/18723	1.59e-20	2.49e-18	68
GO:0046034112	Skin	cSCC	ATP metabolic process	142/4864	277/18723	1.38e-19	1.96e-17	142
GO:002290426	Skin	cSCC	respiratory electron transport chain	74/4864	114/18723	2.52e-18	3.29e-16	74
GO:001598026	Skin	cSCC	energy derivation by oxidation of organic compounds	154/4864	318/18723	4.19e-18	5.15e-16	154
GO:001964626	Skin	cSCC	aerobic electron transport chain	61/4864	87/18723	7.73e-18	8.97e-16	61
GO:000612026	Skin	cSCC	mitochondrial electron transport, NADH to ubiquinone	40/4864	51/18723	6.69e-15	5.06e-13	40
GO:00460346	Stomach	GC	ATP metabolic process	73/1159	277/18723	5.03e-27	1.37e-23	73
GO:00061196	Stomach	GC	oxidative phosphorylation	46/1159	141/18723	1.23e-21	2.24e-18	46
GO:00060916	Stomach	GC	generation of precursor metabolites and energy	88/1159	490/18723	6.82e-20	9.27e-17	88
GO:00090606	Stomach	GC	aerobic respiration	49/1159	189/18723	3.25e-18	3.54e-15	49
GO:00453336	Stomach	GC	cellular respiration	54/1159	230/18723	7.63e-18	6.91e-15	54
GO:00159806	Stomach	GC	energy derivation by oxidation of organic compounds	64/1159	318/18723	2.79e-17	2.16e-14	64
GO:00229006	Stomach	GC	electron transport chain	41/1159	175/18723	7.75e-14	4.68e-11	41
GO:00196466	Stomach	GC	aerobic electron transport chain	28/1159	87/18723	1.55e-13	7.03e-11	28
GO:00229046	Stomach	GC	respiratory electron transport chain	31/1159	114/18723	1.27e-12	4.30e-10	31
GO:00427736	Stomach	GC	ATP synthesis coupled electron transport	28/1159	95/18723	1.79e-12	5.40e-10	28

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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
hsa0472316	Breast	Precancer	Retrograde endocannabinoid signaling	25/684	148/8465	3.05e-04	2.47e-03	1.89e-03	25
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

NDUFV2

SNV

Missense_Mutation

c.743N>T

p.Gly248Val

p.G248V

P19404

protein_coding

deleterious(0.01)

benign(0.197)

TCGA-A2-A04U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NDUFV2

SNV

Missense_Mutation

c.391N>G

p.His131Asp

p.H131D

P19404

protein_coding

deleterious(0.01)

possibly_damaging(0.883)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

NDUFV2

SNV

Missense_Mutation

c.647N>A

p.Pro216Gln

p.P216Q

P19404

protein_coding

deleterious(0.02)

benign(0.091)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NDUFV2

SNV

Missense_Mutation

c.691N>G

p.Leu231Val

p.L231V

P19404

protein_coding

tolerated(0.12)

benign(0.067)

TCGA-VS-A953-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NDUFV2

SNV

Missense_Mutation

novel

c.697N>C

p.Ser233Pro

p.S233P

P19404

protein_coding

deleterious(0)

possibly_damaging(0.786)

TCGA-CI-6620-01

Colorectum

rectum adenocarcinoma

Female

<65

I/II

Ancillary

leucovorin

NDUFV2

SNV

Missense_Mutation

novel

c.193N>A

p.Ala65Thr

p.A65T

P19404

protein_coding

tolerated(0.13)

benign(0.196)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFV2

SNV

Missense_Mutation

novel

c.583N>T

p.Asp195Tyr

p.D195Y

P19404

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

NDUFV2

SNV

Missense_Mutation

novel

c.163T>C

p.Phe55Leu

p.F55L

P19404

protein_coding

deleterious(0.02)

probably_damaging(0.968)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFV2

SNV

Missense_Mutation

novel

c.725N>A

p.Gly242Glu

p.G242E

P19404

protein_coding

deleterious(0.01)

probably_damaging(0.978)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NDUFV2

SNV

Missense_Mutation

novel

c.194N>T

p.Ala65Val

p.A65V

P19404

protein_coding

tolerated(0.09)

benign(0.05)

TCGA-AP-A1DH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<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
4729	NDUFV2	ENZYME	inhibitor	CHEMBL3545320	ME-344
4729	NDUFV2	ENZYME	inhibitor	CHEMBL3545135	NV-128
4729	NDUFV2	ENZYME	inhibitor	CHEMBL1703	METFORMIN HYDROCHLORIDE

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