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: NDUFS7

Gene summary for NDUFS7

Gene summary.

Gene information	Species	Human
	Gene symbol	NDUFS7
	Gene ID	374291
	Gene name	NADH:ubiquinone oxidoreductase core subunit S7
	Gene Alias	CI-20
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	O75251

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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
374291	NDUFS7	CA_HPV_1	Human	Cervix	CC	1.10e-09	-2.21e-01	0.0264
374291	NDUFS7	CCI_1	Human	Cervix	CC	7.20e-04	-5.45e-01	0.528
374291	NDUFS7	CCI_3	Human	Cervix	CC	1.93e-05	-5.39e-01	0.516
374291	NDUFS7	CCII_1	Human	Cervix	CC	1.79e-10	-5.63e-01	0.3249
374291	NDUFS7	H2	Human	Cervix	HSIL_HPV	2.44e-04	-2.77e-01	0.0632
374291	NDUFS7	L1	Human	Cervix	CC	1.48e-04	-1.83e-01	0.0802
374291	NDUFS7	LZE2T	Human	Esophagus	ESCC	2.29e-03	1.04e+00	0.082
374291	NDUFS7	LZE4T	Human	Esophagus	ESCC	1.02e-18	7.28e-01	0.0811
374291	NDUFS7	LZE5T	Human	Esophagus	ESCC	3.76e-05	1.11e+00	0.0514
374291	NDUFS7	LZE7T	Human	Esophagus	ESCC	1.20e-13	1.14e+00	0.0667
374291	NDUFS7	LZE8T	Human	Esophagus	ESCC	8.61e-17	1.03e+00	0.067
374291	NDUFS7	LZE20T	Human	Esophagus	ESCC	5.47e-05	6.09e-01	0.0662
374291	NDUFS7	LZE22D1	Human	Esophagus	HGIN	5.53e-03	6.62e-01	0.0595
374291	NDUFS7	LZE22T	Human	Esophagus	ESCC	1.49e-06	8.52e-01	0.068
374291	NDUFS7	LZE24T	Human	Esophagus	ESCC	4.59e-27	1.05e+00	0.0596
374291	NDUFS7	LZE22D3	Human	Esophagus	HGIN	4.84e-02	1.03e+00	0.0653
374291	NDUFS7	LZE21T	Human	Esophagus	ESCC	5.41e-08	1.19e+00	0.0655
374291	NDUFS7	LZE6T	Human	Esophagus	ESCC	9.25e-09	3.56e-01	0.0845
374291	NDUFS7	P1T-E	Human	Esophagus	ESCC	6.32e-21	1.38e+00	0.0875
374291	NDUFS7	P2T-E	Human	Esophagus	ESCC	5.03e-31	6.73e-01	0.1177

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:004603410	Cervix	CC	ATP metabolic process	90/2311	277/18723	7.90e-19	2.36e-15	90
GO:000611910	Cervix	CC	oxidative phosphorylation	55/2311	141/18723	7.12e-16	1.42e-12	55
GO:00090609	Cervix	CC	aerobic respiration	60/2311	189/18723	1.59e-12	6.36e-10	60
GO:00427739	Cervix	CC	ATP synthesis coupled electron transport	38/2311	95/18723	8.45e-12	2.66e-09	38
GO:00427759	Cervix	CC	mitochondrial ATP synthesis coupled electron transport	38/2311	95/18723	8.45e-12	2.66e-09	38
GO:00196469	Cervix	CC	aerobic electron transport chain	36/2311	87/18723	9.15e-12	2.74e-09	36
GO:00229049	Cervix	CC	respiratory electron transport chain	42/2311	114/18723	1.67e-11	4.77e-09	42
GO:00453339	Cervix	CC	cellular respiration	66/2311	230/18723	2.07e-11	5.39e-09	66
GO:00229009	Cervix	CC	electron transport chain	53/2311	175/18723	2.23e-10	3.43e-08	53
GO:00060919	Cervix	CC	generation of precursor metabolites and energy	105/2311	490/18723	7.40e-09	6.61e-07	105
GO:00159809	Cervix	CC	energy derivation by oxidation of organic compounds	74/2311	318/18723	3.83e-08	2.53e-06	74
GO:00061209	Cervix	CC	mitochondrial electron transport, NADH to ubiquinone	22/2311	51/18723	4.01e-08	2.54e-06	22
GO:00102579	Cervix	CC	NADH dehydrogenase complex assembly	22/2311	57/18723	4.28e-07	1.67e-05	22
GO:00329819	Cervix	CC	mitochondrial respiratory chain complex I assembly	22/2311	57/18723	4.28e-07	1.67e-05	22
GO:19026009	Cervix	CC	proton transmembrane transport	39/2311	157/18723	1.23e-05	2.57e-04	39
GO:00331089	Cervix	CC	mitochondrial respiratory chain complex assembly	26/2311	93/18723	3.97e-05	6.18e-04	26
GO:004603415	Cervix	HSIL_HPV	ATP metabolic process	36/737	277/18723	3.06e-10	7.02e-08	36
GO:000611914	Cervix	HSIL_HPV	oxidative phosphorylation	23/737	141/18723	6.76e-09	8.80e-07	23
GO:001964614	Cervix	HSIL_HPV	aerobic electron transport chain	15/737	87/18723	1.38e-06	6.26e-05	15
GO:000906014	Cervix	HSIL_HPV	aerobic respiration	23/737	189/18723	1.59e-06	6.90e-05	23

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0520820	Cervix	CC	Chemical carcinogenesis - reactive oxygen species	92/1267	223/8465	4.71e-22	5.09e-20	3.01e-20	92
hsa0501220	Cervix	CC	Parkinson disease	102/1267	266/8465	1.81e-21	1.47e-19	8.66e-20	102
hsa0019018	Cervix	CC	Oxidative phosphorylation	64/1267	134/8465	1.25e-19	8.07e-18	4.77e-18	64
hsa0502018	Cervix	CC	Prion disease	98/1267	273/8465	2.64e-18	1.42e-16	8.42e-17	98
hsa0541520	Cervix	CC	Diabetic cardiomyopathy	76/1267	203/8465	1.40e-15	6.46e-14	3.82e-14	76
hsa0501018	Cervix	CC	Alzheimer disease	113/1267	384/8465	9.67e-14	3.92e-12	2.32e-12	113
hsa0501618	Cervix	CC	Huntington disease	94/1267	306/8465	8.49e-13	3.06e-11	1.81e-11	94
hsa0502218	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa0493218	Cervix	CC	Non-alcoholic fatty liver disease	58/1267	155/8465	3.58e-12	1.05e-10	6.23e-11	58
hsa0471420	Cervix	CC	Thermogenesis	76/1267	232/8465	4.29e-12	1.16e-10	6.85e-11	76
hsa0501418	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
hsa0472318	Cervix	CC	Retrograde endocannabinoid signaling	42/1267	148/8465	1.79e-05	1.42e-04	8.40e-05	42
hsa05208110	Cervix	CC	Chemical carcinogenesis - reactive oxygen species	92/1267	223/8465	4.71e-22	5.09e-20	3.01e-20	92
hsa05012110	Cervix	CC	Parkinson disease	102/1267	266/8465	1.81e-21	1.47e-19	8.66e-20	102
hsa0019019	Cervix	CC	Oxidative phosphorylation	64/1267	134/8465	1.25e-19	8.07e-18	4.77e-18	64
hsa0502019	Cervix	CC	Prion disease	98/1267	273/8465	2.64e-18	1.42e-16	8.42e-17	98
hsa05415110	Cervix	CC	Diabetic cardiomyopathy	76/1267	203/8465	1.40e-15	6.46e-14	3.82e-14	76
hsa0501019	Cervix	CC	Alzheimer disease	113/1267	384/8465	9.67e-14	3.92e-12	2.32e-12	113
hsa0501619	Cervix	CC	Huntington disease	94/1267	306/8465	8.49e-13	3.06e-11	1.81e-11	94
hsa0502219	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128

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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

NDUFS7

deletion

Frame_Shift_Del

novel

c.625delN

p.Ile209SerfsTer?

p.I209Sfs*?

O75251

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

NDUFS7

SNV

Missense_Mutation

c.627N>G

p.Ile209Met

p.I209M

O75251

protein_coding

tolerated_low_confidence(0.74)

benign(0.003)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

NDUFS7

SNV

Missense_Mutation

c.332N>A

p.Arg111His

p.R111H

O75251

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(1)

TCGA-F4-6703-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

NDUFS7

SNV

Missense_Mutation

rs778260862

c.29N>A

p.Arg10His

p.R10H

O75251

protein_coding

tolerated_low_confidence(0.14)

benign(0.13)

TCGA-G4-6320-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

oxaliplatin

NDUFS7

SNV

Missense_Mutation

rs769398012

c.614N>A

p.Arg205Gln

p.R205Q

O75251

protein_coding

tolerated_low_confidence(0.13)

benign(0.001)

TCGA-EI-6882-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

NDUFS7

SNV

Missense_Mutation

rs745768565

c.466N>A

p.Gly156Arg

p.G156R

O75251

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(0.999)

TCGA-AJ-A3NF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

chemo

NDUFS7

SNV

Missense_Mutation

novel

c.403C>T

p.Arg135Cys

p.R135C

O75251

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(1)

TCGA-D1-A15X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFS7

SNV

Missense_Mutation

c.530A>G

p.Asp177Gly

p.D177G

O75251

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(1)

TCGA-D1-A15X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFS7

SNV

Missense_Mutation

novel

c.479N>G

p.Tyr160Cys

p.Y160C

O75251

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-D1-A175-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

NDUFS7

SNV

Missense_Mutation

novel

c.550C>T

p.Pro184Ser

p.P184S

O75251

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.997)

TCGA-D1-A1NZ-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
374291	NDUFS7	ENZYME	inhibitor	CHEMBL3545320	ME-344
374291	NDUFS7	ENZYME	inhibitor	CHEMBL3545135	NV-128
374291	NDUFS7	ENZYME	inhibitor	CHEMBL1703	METFORMIN HYDROCHLORIDE

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