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: NDUFA11

Gene summary for NDUFA11

Gene summary.

Gene information	Species	Human
	Gene symbol	NDUFA11
	Gene ID	126328
	Gene name	NADH:ubiquinone oxidoreductase subunit A11
	Gene Alias	B14.7
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	Q86Y39

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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
126328	NDUFA11	GSM4909285	Human	Breast	IDC	5.43e-04	-1.82e-01	0.21
126328	NDUFA11	GSM4909286	Human	Breast	IDC	3.52e-03	2.80e-01	0.1081
126328	NDUFA11	GSM4909291	Human	Breast	IDC	7.26e-08	4.00e-01	0.1753
126328	NDUFA11	GSM4909293	Human	Breast	IDC	4.32e-02	-1.45e-01	0.1581
126328	NDUFA11	GSM4909294	Human	Breast	IDC	2.31e-12	1.64e-01	0.2022
126328	NDUFA11	GSM4909296	Human	Breast	IDC	1.42e-19	1.82e-01	0.1524
126328	NDUFA11	GSM4909297	Human	Breast	IDC	3.95e-23	-8.84e-02	0.1517
126328	NDUFA11	GSM4909298	Human	Breast	IDC	1.99e-19	4.97e-01	0.1551
126328	NDUFA11	GSM4909301	Human	Breast	IDC	1.48e-17	3.80e-01	0.1577
126328	NDUFA11	GSM4909304	Human	Breast	IDC	2.40e-13	4.06e-01	0.1636
126328	NDUFA11	GSM4909306	Human	Breast	IDC	1.22e-19	4.30e-01	0.1564
126328	NDUFA11	GSM4909308	Human	Breast	IDC	3.17e-03	2.71e-01	0.158
126328	NDUFA11	GSM4909311	Human	Breast	IDC	3.19e-54	4.36e-02	0.1534
126328	NDUFA11	GSM4909312	Human	Breast	IDC	8.48e-20	2.19e-01	0.1552
126328	NDUFA11	GSM4909313	Human	Breast	IDC	8.17e-06	3.97e-02	0.0391
126328	NDUFA11	GSM4909315	Human	Breast	IDC	1.76e-26	5.28e-01	0.21
126328	NDUFA11	GSM4909316	Human	Breast	IDC	3.47e-36	8.08e-01	0.21
126328	NDUFA11	GSM4909319	Human	Breast	IDC	1.62e-55	-4.25e-01	0.1563
126328	NDUFA11	GSM4909320	Human	Breast	IDC	5.60e-84	1.20e+00	0.1575
126328	NDUFA11	GSM4909321	Human	Breast	IDC	5.86e-126	1.10e+00	0.1559

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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:00102578	Breast	Precancer	NADH dehydrogenase complex assembly	19/1080	57/18723	1.93e-10	1.92e-08	19
GO:00329818	Breast	Precancer	mitochondrial respiratory chain complex I assembly	19/1080	57/18723	1.93e-10	1.92e-08	19
GO:00331088	Breast	Precancer	mitochondrial respiratory chain complex assembly	24/1080	93/18723	3.39e-10	3.16e-08	24
GO:001025713	Breast	IDC	NADH dehydrogenase complex assembly	22/1434	57/18723	6.20e-11	8.80e-09	22
GO:003298113	Breast	IDC	mitochondrial respiratory chain complex I assembly	22/1434	57/18723	6.20e-11	8.80e-09	22
GO:003310813	Breast	IDC	mitochondrial respiratory chain complex assembly	28/1434	93/18723	1.54e-10	1.83e-08	28
GO:001025723	Breast	DCIS	NADH dehydrogenase complex assembly	22/1390	57/18723	3.38e-11	5.17e-09	22
GO:003298123	Breast	DCIS	mitochondrial respiratory chain complex I assembly	22/1390	57/18723	3.38e-11	5.17e-09	22
GO:003310823	Breast	DCIS	mitochondrial respiratory chain complex assembly	28/1390	93/18723	7.50e-11	9.43e-09	28
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:00331089	Cervix	CC	mitochondrial respiratory chain complex assembly	26/2311	93/18723	3.97e-05	6.18e-04	26
GO:001025714	Cervix	N_HPV	NADH dehydrogenase complex assembly	10/534	57/18723	4.24e-06	1.65e-04	10
GO:003298114	Cervix	N_HPV	mitochondrial respiratory chain complex I assembly	10/534	57/18723	4.24e-06	1.65e-04	10
GO:003310814	Cervix	N_HPV	mitochondrial respiratory chain complex assembly	10/534	93/18723	3.17e-04	4.75e-03	10
GO:0010257	Colorectum	AD	NADH dehydrogenase complex assembly	34/3918	57/18723	2.15e-10	1.89e-08	34
GO:0032981	Colorectum	AD	mitochondrial respiratory chain complex I assembly	34/3918	57/18723	2.15e-10	1.89e-08	34
GO:0033108	Colorectum	AD	mitochondrial respiratory chain complex assembly	46/3918	93/18723	8.95e-10	6.91e-08	46
GO:00102571	Colorectum	SER	NADH dehydrogenase complex assembly	30/2897	57/18723	7.92e-11	1.19e-08	30
GO:00329811	Colorectum	SER	mitochondrial respiratory chain complex I assembly	30/2897	57/18723	7.92e-11	1.19e-08	30

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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

NDUFA11

SNV

Missense_Mutation

novel

c.170N>C

p.Gly57Ala

p.G57A

Q86Y39

protein_coding

tolerated_low_confidence(0.29)

probably_damaging(0.998)

TCGA-C8-A8HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NDUFA11

SNV

Missense_Mutation

novel

c.411G>A

p.Met137Ile

p.M137I

Q86Y39

protein_coding

tolerated_low_confidence(0.07)

benign(0)

TCGA-VS-A8QM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NDUFA11

SNV

Missense_Mutation

c.221N>T

p.Thr74Ile

p.T74I

Q86Y39

protein_coding

deleterious_low_confidence(0)

benign(0.153)

TCGA-AZ-5407-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

NDUFA11

SNV

Missense_Mutation

novel

c.643N>T

p.Ile215Leu

p.I215L

Q86Y39

protein_coding

benign(0)

TCGA-EO-A22X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unspecific

Carboplatin

Complete Response

NDUFA11

deletion

Frame_Shift_Del

novel

c.514delG

p.Ala172HisfsTer21

p.A172Hfs*21

Q86Y39

protein_coding

TCGA-AP-A1DH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFA11

deletion

Frame_Shift_Del

novel

c.514delN

p.Ala172HisfsTer21

p.A172Hfs*21

Q86Y39

protein_coding

TCGA-DI-A1BU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

NDUFA11

insertion

Frame_Shift_Ins

novel

c.514dupG

p.Ala172GlyfsTer256

p.A172Gfs*256

Q86Y39

protein_coding

TCGA-EO-A22U-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
126328	NDUFA11	ENZYME	inhibitor	CHEMBL1703	METFORMIN HYDROCHLORIDE
126328	NDUFA11	ENZYME	inhibitor	CHEMBL3545320	ME-344
126328	NDUFA11	ENZYME	inhibitor	CHEMBL3545135	NV-128

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