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: NDUFV1

Gene summary for NDUFV1

Gene summary.

Gene information	Species	Human
	Gene symbol	NDUFV1
	Gene ID	4723
	Gene name	NADH:ubiquinone oxidoreductase core subunit V1
	Gene Alias	CI-51K
	Cytomap	11q13.2
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	P49821

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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
4723	NDUFV1	HTA11_2487_2000001011	Human	Colorectum	SER	2.96e-04	4.00e-01	-0.1808
4723	NDUFV1	HTA11_1938_2000001011	Human	Colorectum	AD	3.44e-08	5.63e-01	-0.0811
4723	NDUFV1	HTA11_347_2000001011	Human	Colorectum	AD	2.51e-21	6.53e-01	-0.1954
4723	NDUFV1	HTA11_411_2000001011	Human	Colorectum	SER	3.11e-02	5.99e-01	-0.2602
4723	NDUFV1	HTA11_3361_2000001011	Human	Colorectum	AD	1.70e-04	4.80e-01	-0.1207
4723	NDUFV1	HTA11_83_2000001011	Human	Colorectum	SER	6.17e-04	5.26e-01	-0.1526
4723	NDUFV1	HTA11_696_2000001011	Human	Colorectum	AD	9.87e-21	7.72e-01	-0.1464
4723	NDUFV1	HTA11_1391_2000001011	Human	Colorectum	AD	1.06e-11	6.14e-01	-0.059
4723	NDUFV1	HTA11_546_2000001011	Human	Colorectum	AD	1.42e-04	5.76e-01	-0.0842
4723	NDUFV1	HTA11_7862_2000001011	Human	Colorectum	AD	6.15e-05	5.16e-01	-0.0179
4723	NDUFV1	HTA11_866_3004761011	Human	Colorectum	AD	1.95e-04	2.55e-01	0.096
4723	NDUFV1	HTA11_8622_2000001021	Human	Colorectum	SER	1.34e-05	5.36e-01	0.0528
4723	NDUFV1	HTA11_7663_2000001011	Human	Colorectum	SER	9.31e-04	5.44e-01	0.0131
4723	NDUFV1	HTA11_6801_2000001011	Human	Colorectum	SER	3.76e-02	7.27e-01	0.0171
4723	NDUFV1	HTA11_10711_2000001011	Human	Colorectum	AD	3.63e-05	5.04e-01	0.0338
4723	NDUFV1	HTA11_7696_3000711011	Human	Colorectum	AD	1.18e-13	5.95e-01	0.0674
4723	NDUFV1	HTA11_7469_2000001011	Human	Colorectum	AD	4.47e-04	8.49e-01	-0.0124
4723	NDUFV1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.18e-04	3.63e-01	0.294
4723	NDUFV1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.62e-02	3.77e-01	0.3859
4723	NDUFV1	A015-C-203	Human	Colorectum	FAP	4.37e-06	1.60e-01	-0.1294

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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
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:00060914	Colorectum	FAP	generation of precursor metabolites and energy	128/2622	490/18723	5.58e-13	4.28e-10	128
GO:00060912	Colorectum	MSS	generation of precursor metabolites and energy	186/3467	490/18723	1.14e-24	2.15e-21	186
GO:00460342	Colorectum	MSS	ATP metabolic process	125/3467	277/18723	1.38e-24	2.15e-21	125
GO:00453332	Colorectum	MSS	cellular respiration	107/3467	230/18723	1.64e-22	2.05e-19	107
GO:00159802	Colorectum	MSS	energy derivation by oxidation of organic compounds	131/3467	318/18723	2.60e-21	2.70e-18	131
GO:00061192	Colorectum	MSS	oxidative phosphorylation	76/3467	141/18723	3.49e-21	3.11e-18	76
GO:00229002	Colorectum	MSS	electron transport chain	83/3467	175/18723	2.06e-18	1.17e-15	83
GO:00229042	Colorectum	MSS	respiratory electron transport chain	61/3467	114/18723	4.46e-17	1.99e-14	61
GO:00427732	Colorectum	MSS	ATP synthesis coupled electron transport	54/3467	95/18723	8.09e-17	3.16e-14	54
GO:00427752	Colorectum	MSS	mitochondrial ATP synthesis coupled electron transport	54/3467	95/18723	8.09e-17	3.16e-14	54
GO:00196462	Colorectum	MSS	aerobic electron transport chain	51/3467	87/18723	9.74e-17	3.57e-14	51
GO:00061202	Colorectum	MSS	mitochondrial electron transport, NADH to ubiquinone	31/3467	51/18723	2.73e-11	3.67e-09	31
GO:00460344	Colorectum	FAP	ATP metabolic process	87/2622	277/18723	6.50e-14	6.63e-11	87
GO:00229044	Colorectum	FAP	respiratory electron transport chain	35/2622	114/18723	3.43e-06	1.23e-04	35
GO:0046034	Colorectum	AD	ATP metabolic process	142/3918	277/18723	2.64e-29	8.26e-26	142
GO:00061204	Colorectum	FAP	mitochondrial electron transport, NADH to ubiquinone	14/2622	51/18723	8.70e-03	4.98e-02	14
GO:00196464	Colorectum	FAP	aerobic electron transport chain	25/2622	87/18723	2.63e-04	3.59e-03	25
GO:00427754	Colorectum	FAP	mitochondrial ATP synthesis coupled electron transport	28/2622	95/18723	7.10e-05	1.32e-03	28
GO:00427734	Colorectum	FAP	ATP synthesis coupled electron transport	28/2622	95/18723	7.10e-05	1.32e-03	28
GO:00453334	Colorectum	FAP	cellular respiration	65/2622	230/18723	1.13e-08	1.33e-06	65

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05012211	Esophagus	ESCC	Parkinson disease	201/4205	266/8465	1.56e-18	8.72e-17	4.46e-17	201
hsa05208211	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa05022210	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa05010210	Esophagus	ESCC	Alzheimer disease	263/4205	384/8465	1.80e-14	5.47e-13	2.80e-13	263
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa05020210	Esophagus	ESCC	Prion disease	193/4205	273/8465	6.42e-13	1.34e-11	6.89e-12	193
hsa00190210	Esophagus	ESCC	Oxidative phosphorylation	104/4205	134/8465	2.04e-11	2.98e-10	1.53e-10	104
hsa05415211	Esophagus	ESCC	Diabetic cardiomyopathy	146/4205	203/8465	5.81e-11	7.78e-10	3.99e-10	146
hsa04714211	Esophagus	ESCC	Thermogenesis	163/4205	232/8465	9.22e-11	1.14e-09	5.86e-10	163
hsa0501438	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0501638	Esophagus	ESCC	Huntington disease	226/4205	306/8465	1.38e-18	8.72e-17	4.46e-17	226
hsa05012310	Esophagus	ESCC	Parkinson disease	201/4205	266/8465	1.56e-18	8.72e-17	4.46e-17	201
hsa05208310	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa0502238	Esophagus	ESCC	Pathways of neurodegeneration - multiple diseases	318/4205	476/8465	6.10e-15	2.04e-13	1.05e-13	318
hsa0501038	Esophagus	ESCC	Alzheimer disease	263/4205	384/8465	1.80e-14	5.47e-13	2.80e-13	263
hsa0493238	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0502038	Esophagus	ESCC	Prion disease	193/4205	273/8465	6.42e-13	1.34e-11	6.89e-12	193
hsa0019038	Esophagus	ESCC	Oxidative phosphorylation	104/4205	134/8465	2.04e-11	2.98e-10	1.53e-10	104
hsa0541538	Esophagus	ESCC	Diabetic cardiomyopathy	146/4205	203/8465	5.81e-11	7.78e-10	3.99e-10	146
hsa04714310	Esophagus	ESCC	Thermogenesis	163/4205	232/8465	9.22e-11	1.14e-09	5.86e-10	163

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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

NDUFV1

SNV

Missense_Mutation

rs747661849

c.451G>A

p.Ala151Thr

p.A151T

P49821

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(1)

TCGA-BH-A0WA-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NDUFV1

SNV

Missense_Mutation

c.800N>C

p.Arg267Thr

p.R267T

P49821

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.998)

TCGA-C8-A1HK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NDUFV1

SNV

Missense_Mutation

c.552N>C

p.Lys184Asn

p.K184N

P49821

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.857)

TCGA-D8-A1Y0-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide+methotrexatum+fluorouracillum

NDUFV1

SNV

Missense_Mutation

c.123N>G

p.Ile41Met

p.I41M

P49821

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.937)

TCGA-GI-A2C8-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

Adriamycin

NDUFV1

insertion

Nonsense_Mutation

novel

c.159_160insCTCTGGGCCTCCTGACCCTTTGTCTCCCT

p.Lys54LeufsTer5

p.K54Lfs*5

P49821

protein_coding

TCGA-AN-A0AR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NDUFV1

insertion

Frame_Shift_Ins

novel

c.293_294insCAGAGTTCTTATGAGGATGAAATGGGATTTTGGAT

p.Lys98AsnfsTer17

p.K98Nfs*17

P49821

protein_coding

TCGA-BH-A0EB-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NDUFV1

insertion

Frame_Shift_Ins

novel

c.1087_1088insGAGCAGAAGGATTAAAACAGGC

p.Ile363ArgfsTer17

p.I363Rfs*17

P49821

protein_coding

TCGA-EA-A1QT-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NDUFV1

SNV

Missense_Mutation

rs376958800

c.1102N>A

p.Ala368Thr

p.A368T

P49821

protein_coding

deleterious_low_confidence(0.04)

benign(0.202)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

NDUFV1

SNV

Missense_Mutation

rs568068157

c.596N>A

p.Arg199His

p.R199H

P49821

protein_coding

tolerated_low_confidence(0.21)

probably_damaging(1)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

NDUFV1

SNV

Missense_Mutation

c.806G>A

p.Arg269His

p.R269H

P49821

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.999)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

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
4723	NDUFV1	ENZYME	inhibitor	CHEMBL3545135	NV-128
4723	NDUFV1	ENZYME	inhibitor	CHEMBL3545320	ME-344
4723	NDUFV1	ENZYME	inhibitor	CHEMBL1703	METFORMIN HYDROCHLORIDE

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