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: NDUFB6

Gene summary for NDUFB6

Gene summary.

Gene information	Species	Human
	Gene symbol	NDUFB6
	Gene ID	4712
	Gene name	NADH:ubiquinone oxidoreductase subunit B6
	Gene Alias	B17
	Cytomap	9p21.1
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	A0A087WZX2

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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
4712	NDUFB6	GSM4909281	Human	Breast	IDC	4.83e-10	4.39e-01	0.21
4712	NDUFB6	GSM4909282	Human	Breast	IDC	1.18e-09	4.25e-01	-0.0288
4712	NDUFB6	GSM4909288	Human	Breast	IDC	3.34e-04	1.26e-01	0.0988
4712	NDUFB6	GSM4909290	Human	Breast	IDC	1.03e-16	6.21e-01	0.2096
4712	NDUFB6	GSM4909293	Human	Breast	IDC	2.13e-05	2.40e-01	0.1581
4712	NDUFB6	GSM4909296	Human	Breast	IDC	1.22e-10	2.28e-01	0.1524
4712	NDUFB6	GSM4909297	Human	Breast	IDC	5.45e-10	-1.38e-02	0.1517
4712	NDUFB6	GSM4909301	Human	Breast	IDC	6.91e-04	2.57e-01	0.1577
4712	NDUFB6	GSM4909308	Human	Breast	IDC	5.76e-06	3.51e-01	0.158
4712	NDUFB6	GSM4909311	Human	Breast	IDC	2.13e-22	-8.98e-02	0.1534
4712	NDUFB6	GSM4909312	Human	Breast	IDC	4.73e-08	7.87e-02	0.1552
4712	NDUFB6	GSM4909313	Human	Breast	IDC	1.65e-04	-1.12e-01	0.0391
4712	NDUFB6	GSM4909319	Human	Breast	IDC	7.27e-38	-6.17e-02	0.1563
4712	NDUFB6	GSM4909320	Human	Breast	IDC	4.04e-13	1.33e-01	0.1575
4712	NDUFB6	GSM4909321	Human	Breast	IDC	4.54e-14	-3.62e-03	0.1559
4712	NDUFB6	brca1	Human	Breast	Precancer	2.60e-06	3.98e-01	-0.0338
4712	NDUFB6	brca2	Human	Breast	Precancer	3.49e-10	3.51e-01	-0.024
4712	NDUFB6	NCCBC11	Human	Breast	DCIS	1.38e-03	1.48e-01	0.1232
4712	NDUFB6	NCCBC14	Human	Breast	DCIS	1.20e-05	-2.69e-02	0.2021
4712	NDUFB6	NCCBC5	Human	Breast	DCIS	2.94e-10	1.25e-02	0.2046

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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
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
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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00061199	Breast	Precancer	oxidative phosphorylation	53/1080	141/18723	1.15e-29	2.04e-26	53
GO:00090608	Breast	Precancer	aerobic respiration	58/1080	189/18723	5.69e-27	7.62e-24	58
GO:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00453338	Breast	Precancer	cellular respiration	59/1080	230/18723	5.97e-23	5.32e-20	59
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:00196468	Breast	Precancer	aerobic electron transport chain	34/1080	87/18723	3.95e-20	2.64e-17	34
GO:00427738	Breast	Precancer	ATP synthesis coupled electron transport	35/1080	95/18723	1.08e-19	5.76e-17	35
GO:00427758	Breast	Precancer	mitochondrial ATP synthesis coupled electron transport	35/1080	95/18723	1.08e-19	5.76e-17	35
GO:00229048	Breast	Precancer	respiratory electron transport chain	35/1080	114/18723	8.51e-17	3.26e-14	35
GO:00229008	Breast	Precancer	electron transport chain	42/1080	175/18723	1.37e-15	4.59e-13	42
GO:00061208	Breast	Precancer	mitochondrial electron transport, NADH to ubiquinone	19/1080	51/18723	2.05e-11	2.49e-09	19
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:004603414	Breast	IDC	ATP metabolic process	85/1434	277/18723	6.42e-30	1.82e-26	85
GO:000611913	Breast	IDC	oxidative phosphorylation	56/1434	141/18723	1.87e-26	3.53e-23	56
GO:000906013	Breast	IDC	aerobic respiration	61/1434	189/18723	4.42e-23	6.27e-20	61
GO:000609113	Breast	IDC	generation of precursor metabolites and energy	103/1434	490/18723	1.53e-21	1.74e-18	103
GO:004533313	Breast	IDC	cellular respiration	62/1434	230/18723	5.98e-19	4.25e-16	62

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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

NDUFB6

SNV

Missense_Mutation

c.224T>C

p.Val75Ala

p.V75A

O95139

protein_coding

deleterious(0.02)

benign(0.005)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NDUFB6

SNV

Missense_Mutation

c.247N>T

p.His83Tyr

p.H83Y

O95139

protein_coding

tolerated(0.07)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NDUFB6

SNV

Missense_Mutation

novel

c.314T>A

p.Phe105Tyr

p.F105Y

O95139

protein_coding

tolerated(0.29)

probably_damaging(0.995)

TCGA-GM-A2DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

NDUFB6

SNV

Missense_Mutation

novel

c.79N>A

p.Glu27Lys

p.E27K

O95139

protein_coding

deleterious(0.01)

possibly_damaging(0.67)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NDUFB6

insertion

Frame_Shift_Ins

novel

c.215_216insT

p.Thr73HisfsTer20

p.T73Hfs*20

O95139

protein_coding

TCGA-AZ-4615-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

xeloda

NDUFB6

SNV

Missense_Mutation

novel

c.336N>T

p.Glu112Asp

p.E112D

O95139

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

NDUFB6

SNV

Missense_Mutation

novel

c.173N>T

p.Arg58Met

p.R58M

O95139

protein_coding

deleterious(0)

possibly_damaging(0.87)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFB6

SNV

Missense_Mutation

novel

c.56N>T

p.Arg19Ile

p.R19I

O95139

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NDUFB6

SNV

Missense_Mutation

novel

c.100N>A

p.Val34Met

p.V34M

O95139

protein_coding

deleterious(0)

possibly_damaging(0.875)

TCGA-AX-A1C5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unspecific

Carboplatin

NDUFB6

SNV

Missense_Mutation

novel

c.300N>T

p.Lys100Asn

p.K100N

O95139

protein_coding

tolerated(0.42)

benign(0.012)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

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
4712	NDUFB6	ENZYME	inhibitor	CHEMBL3545135	NV-128
4712	NDUFB6	ENZYME	inhibitor	CHEMBL3545320	ME-344
4712	NDUFB6	ENZYME	inhibitor	CHEMBL1703	METFORMIN HYDROCHLORIDE

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