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: NDUFB11

Gene summary for NDUFB11

Gene summary.

Gene information	Species	Human
	Gene symbol	NDUFB11
	Gene ID	54539
	Gene name	NADH:ubiquinone oxidoreductase subunit B11
	Gene Alias	CI-ESSS
	Cytomap	Xp11.3
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	Q9NX14

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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
54539	NDUFB11	CA_HPV_1	Human	Cervix	CC	4.87e-13	-3.53e-01	0.0264
54539	NDUFB11	CA_HPV_2	Human	Cervix	CC	5.12e-06	-2.67e-01	0.0391
54539	NDUFB11	CA_HPV_3	Human	Cervix	CC	1.08e-02	2.94e-02	0.0414
54539	NDUFB11	N_HPV_1	Human	Cervix	N_HPV	1.68e-02	-1.71e-01	0.0079
54539	NDUFB11	N_HPV_2	Human	Cervix	N_HPV	3.92e-02	1.90e-02	-0.0131
54539	NDUFB11	CCI_1	Human	Cervix	CC	5.98e-19	-9.97e-01	0.528
54539	NDUFB11	CCI_2	Human	Cervix	CC	2.62e-07	-7.90e-01	0.5249
54539	NDUFB11	CCI_3	Human	Cervix	CC	2.87e-20	-9.65e-01	0.516
54539	NDUFB11	CCII_1	Human	Cervix	CC	4.29e-26	-9.51e-01	0.3249
54539	NDUFB11	sample3	Human	Cervix	CC	2.07e-06	-5.49e-02	0.1387
54539	NDUFB11	L1	Human	Cervix	CC	1.19e-10	-3.40e-01	0.0802
54539	NDUFB11	HTA11_3410_2000001011	Human	Colorectum	AD	2.63e-16	3.58e-01	0.0155
54539	NDUFB11	HTA11_2487_2000001011	Human	Colorectum	SER	9.97e-25	7.01e-01	-0.1808
54539	NDUFB11	HTA11_2951_2000001011	Human	Colorectum	AD	1.78e-02	4.50e-01	0.0216
54539	NDUFB11	HTA11_1938_2000001011	Human	Colorectum	AD	1.42e-17	7.15e-01	-0.0811
54539	NDUFB11	HTA11_78_2000001011	Human	Colorectum	AD	1.08e-04	2.85e-01	-0.1088
54539	NDUFB11	HTA11_347_2000001011	Human	Colorectum	AD	2.46e-36	7.39e-01	-0.1954
54539	NDUFB11	HTA11_411_2000001011	Human	Colorectum	SER	3.90e-21	1.27e+00	-0.2602
54539	NDUFB11	HTA11_2112_2000001011	Human	Colorectum	SER	5.69e-08	9.21e-01	-0.2196
54539	NDUFB11	HTA11_3361_2000001011	Human	Colorectum	AD	6.44e-16	7.17e-01	-0.1207

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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
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: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
GO:00331081	Colorectum	SER	mitochondrial respiratory chain complex assembly	39/2897	93/18723	8.13e-10	8.74e-08	39
GO:00102572	Colorectum	MSS	NADH dehydrogenase complex assembly	33/3467	57/18723	4.07e-11	4.86e-09	33
GO:00329812	Colorectum	MSS	mitochondrial respiratory chain complex I assembly	33/3467	57/18723	4.07e-11	4.86e-09	33
GO:00331082	Colorectum	MSS	mitochondrial respiratory chain complex assembly	44/3467	93/18723	2.17e-10	2.09e-08	44
GO:00102573	Colorectum	MSI-H	NADH dehydrogenase complex assembly	25/1319	57/18723	1.40e-14	3.53e-12	25
GO:00329813	Colorectum	MSI-H	mitochondrial respiratory chain complex I assembly	25/1319	57/18723	1.40e-14	3.53e-12	25
GO:00331083	Colorectum	MSI-H	mitochondrial respiratory chain complex assembly	30/1319	93/18723	5.71e-13	1.27e-10	30
GO:001025710	Endometrium	AEH	NADH dehydrogenase complex assembly	25/2100	57/18723	4.20e-10	4.20e-08	25
GO:003298110	Endometrium	AEH	mitochondrial respiratory chain complex I assembly	25/2100	57/18723	4.20e-10	4.20e-08	25

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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

NDUFB11

SNV

Missense_Mutation

novel

c.406G>T

p.Val136Leu

p.V136L

Q9NX14

protein_coding

tolerated(0.25)

possibly_damaging(0.472)

TCGA-E9-A22A-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

NDUFB11

SNV

Missense_Mutation

rs781871228

c.140G>A

p.Arg47Gln

p.R47Q

Q9NX14

protein_coding

tolerated(0.19)

benign(0.086)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

NDUFB11

SNV

Missense_Mutation

rs782460503

c.386N>A

p.Arg129His

p.R129H

Q9NX14

protein_coding

deleterious(0.02)

benign(0.103)

TCGA-EA-A3HT-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

NDUFB11

SNV

Missense_Mutation

c.263N>C

p.Arg88Pro

p.R88P

Q9NX14

protein_coding

deleterious(0)

probably_damaging(0.946)

TCGA-Q1-A73P-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NDUFB11

SNV

Missense_Mutation

novel

c.11N>A

p.Gly4Glu

p.G4E

Q9NX14

protein_coding

tolerated_low_confidence(0.07)

benign(0.031)

TCGA-AA-A01P-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

NDUFB11

SNV

Missense_Mutation

novel

c.233A>C

p.Lys78Thr

p.K78T

Q9NX14

protein_coding

tolerated(0.19)

benign(0.122)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFB11

SNV

Missense_Mutation

rs782682185

c.283G>A

p.Val95Ile

p.V95I

Q9NX14

protein_coding

tolerated(1)

benign(0.009)

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

NDUFB11

SNV

Missense_Mutation

rs782460503

c.386N>A

p.Arg129His

p.R129H

Q9NX14

protein_coding

deleterious(0.02)

benign(0.103)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFB11

SNV

Missense_Mutation

rs782460503

c.386N>A

p.Arg129His

p.R129H

Q9NX14

protein_coding

deleterious(0.02)

benign(0.103)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

NDUFB11

SNV

Missense_Mutation

c.263N>A

p.Arg88Gln

p.R88Q

Q9NX14

protein_coding

tolerated(0.09)

benign(0.095)

TCGA-AP-A1DV-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
54539	NDUFB11	ENZYME	inhibitor	CHEMBL3545320	ME-344
54539	NDUFB11	ENZYME	inhibitor	CHEMBL3545135	NV-128
54539	NDUFB11	ENZYME	inhibitor	CHEMBL1703	METFORMIN HYDROCHLORIDE

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