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: UQCRB

Gene summary for UQCRB

Gene summary.

Gene information	Species	Human
	Gene symbol	UQCRB
	Gene ID	7381
	Gene name	ubiquinol-cytochrome c reductase binding protein
	Gene Alias	MC3DN3
	Cytomap	8q22.1
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	P14927

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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
7381	UQCRB	GSM4909280	Human	Breast	Precancer	1.41e-02	-1.05e-01	0.0305
7381	UQCRB	GSM4909281	Human	Breast	IDC	1.02e-28	4.38e-01	0.21
7381	UQCRB	GSM4909286	Human	Breast	IDC	1.33e-34	4.42e-01	0.1081
7381	UQCRB	GSM4909287	Human	Breast	IDC	7.16e-72	6.29e-01	0.2057
7381	UQCRB	GSM4909288	Human	Breast	IDC	2.50e-16	4.12e-01	0.0988
7381	UQCRB	GSM4909291	Human	Breast	IDC	1.49e-06	2.50e-01	0.1753
7381	UQCRB	GSM4909294	Human	Breast	IDC	1.77e-52	5.03e-01	0.2022
7381	UQCRB	GSM4909295	Human	Breast	IDC	9.12e-03	1.53e-01	0.0898
7381	UQCRB	GSM4909296	Human	Breast	IDC	3.67e-26	2.49e-01	0.1524
7381	UQCRB	GSM4909297	Human	Breast	IDC	1.10e-32	-4.06e-01	0.1517
7381	UQCRB	GSM4909298	Human	Breast	IDC	1.92e-02	2.71e-01	0.1551
7381	UQCRB	GSM4909299	Human	Breast	IDC	1.26e-07	2.84e-01	0.035
7381	UQCRB	GSM4909301	Human	Breast	IDC	1.46e-10	-3.59e-01	0.1577
7381	UQCRB	GSM4909302	Human	Breast	IDC	9.11e-06	-3.67e-01	0.1545
7381	UQCRB	GSM4909309	Human	Breast	IDC	4.90e-06	-1.84e-01	0.0483
7381	UQCRB	GSM4909311	Human	Breast	IDC	1.44e-68	-2.88e-03	0.1534
7381	UQCRB	GSM4909312	Human	Breast	IDC	4.36e-25	2.26e-01	0.1552
7381	UQCRB	GSM4909313	Human	Breast	IDC	4.60e-03	-2.41e-01	0.0391
7381	UQCRB	GSM4909315	Human	Breast	IDC	3.03e-22	3.72e-01	0.21
7381	UQCRB	GSM4909316	Human	Breast	IDC	2.02e-20	3.48e-01	0.21

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:000609119	Oral cavity	LP	generation of precursor metabolites and energy	214/4623	490/18723	1.12e-20	2.60e-18	214
GO:002290419	Oral cavity	LP	respiratory electron transport chain	75/4623	114/18723	1.92e-20	4.14e-18	75
GO:001964619	Oral cavity	LP	aerobic electron transport chain	62/4623	87/18723	7.13e-20	1.49e-17	62
GO:0006119110	Oral cavity	LP	oxidative phosphorylation	81/4623	141/18723	9.70e-17	1.48e-14	81
GO:001598019	Oral cavity	LP	energy derivation by oxidation of organic compounds	145/4623	318/18723	2.44e-16	3.64e-14	145
GO:0046034110	Oral cavity	LP	ATP metabolic process	128/4623	277/18723	3.95e-15	5.38e-13	128
GO:000612218	Oral cavity	LP	mitochondrial electron transport, ubiquinol to cytochrome c	10/4623	11/18723	7.14e-06	1.37e-04	10
GO:004603426	Oral cavity	EOLP	ATP metabolic process	68/2218	277/18723	2.72e-09	1.71e-07	68
GO:001964625	Oral cavity	EOLP	aerobic electron transport chain	26/2218	87/18723	5.15e-06	1.04e-04	26
GO:004277325	Oral cavity	EOLP	ATP synthesis coupled electron transport	27/2218	95/18723	9.68e-06	1.75e-04	27
GO:004277525	Oral cavity	EOLP	mitochondrial ATP synthesis coupled electron transport	27/2218	95/18723	9.68e-06	1.75e-04	27
GO:000611925	Oral cavity	EOLP	oxidative phosphorylation	33/2218	141/18723	8.63e-05	1.02e-03	33
GO:002290425	Oral cavity	EOLP	respiratory electron transport chain	28/2218	114/18723	1.20e-04	1.33e-03	28
GO:000906025	Oral cavity	EOLP	aerobic respiration	40/2218	189/18723	1.76e-04	1.81e-03	40
GO:000612224	Oral cavity	EOLP	mitochondrial electron transport, ubiquinol to cytochrome c	6/2218	11/18723	7.46e-04	6.03e-03	6
GO:004533325	Oral cavity	EOLP	cellular respiration	44/2218	230/18723	8.67e-04	6.75e-03	44
GO:002290025	Oral cavity	EOLP	electron transport chain	35/2218	175/18723	1.26e-03	9.04e-03	35
GO:000609125	Oral cavity	EOLP	generation of precursor metabolites and energy	79/2218	490/18723	2.65e-03	1.59e-02	79
GO:001598025	Oral cavity	EOLP	energy derivation by oxidation of organic compounds	54/2218	318/18723	4.02e-03	2.23e-02	54
GO:004603433	Oral cavity	NEOLP	ATP metabolic process	71/2005	277/18723	1.44e-12	3.17e-10	71

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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
hsa0426016	Breast	Precancer	Cardiac muscle contraction	22/684	87/8465	9.72e-07	1.62e-05	1.24e-05	22
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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
UQCRB	CD8TCM	Cervix	CC	RPS28,FAU,RPL39, etc.	1.10e-01
UQCRB	CD4TN	Cervix	CC	RPS28,FAU,RPL39, etc.	1.36e-01
UQCRB	GDT	Cervix	CC	RPS28,FAU,RPL39, etc.	1.20e-01
UQCRB	CD8TEFF	Cervix	CC	RPS28,FAU,RPL39, etc.	8.84e-02
UQCRB	CD8TEXP	Cervix	CC	RPS28,FAU,RPL39, etc.	5.28e-02
UQCRB	TFH	Cervix	CC	RPS28,FAU,RPL39, etc.	6.94e-02
UQCRB	CD8TEFF	Endometrium	EEC	RPL34,COX7C,RPL39, etc.	1.48e-01
UQCRB	CD4TN	Endometrium	EEC	RPL34,COX7C,RPL39, etc.	9.24e-02
UQCRB	SMC	Esophagus	Healthy	RPS29,RPL37A,RPS28, etc.	1.09e-01
UQCRB	TH1	Lung	IAC	TPT1,ATP5E,RPL21, etc.	1.66e-01

∗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

UQCRB

SNV

Missense_Mutation

c.146N>A

p.Arg49Lys

p.R49K

P14927

protein_coding

tolerated(0.22)

possibly_damaging(0.487)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UQCRB

SNV

Missense_Mutation

c.39N>T

p.Trp13Cys

p.W13C

P14927

protein_coding

deleterious(0.02)

possibly_damaging(0.905)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

UQCRB

SNV

Missense_Mutation

c.130G>T

p.Val44Leu

p.V44L

P14927

protein_coding

deleterious(0.03)

benign(0.255)

TCGA-Q1-A6DT-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

UQCRB

SNV

Missense_Mutation

novel

c.184C>T

p.Arg62Cys

p.R62C

P14927

protein_coding

deleterious(0.02)

probably_damaging(0.995)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

UQCRB

SNV

Missense_Mutation

rs749174411

c.53N>A

p.Arg18Gln

p.R18Q

P14927

protein_coding

tolerated(0.19)

benign(0.145)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

UQCRB

SNV

Missense_Mutation

c.223A>C

p.Ile75Leu

p.I75L

P14927

protein_coding

tolerated(0.29)

possibly_damaging(0.718)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UQCRB

SNV

Missense_Mutation

novel

c.185N>A

p.Arg62His

p.R62H

P14927

protein_coding

deleterious(0.03)

possibly_damaging(0.693)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

UQCRB

SNV

Missense_Mutation

novel

c.60G>C

p.Trp20Cys

p.W20C

P14927

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AX-A2HG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

UQCRB

SNV

Missense_Mutation

novel

c.233A>C

p.Lys78Thr

p.K78T

P14927

protein_coding

deleterious(0)

probably_damaging(0.976)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

UQCRB

SNV

Missense_Mutation

rs376775585

c.79N>G

p.Phe27Val

p.F27V

P14927

protein_coding

deleterious(0.02)

possibly_damaging(0.795)

TCGA-G3-A5SL-01

Liver

liver hepatocellular carcinoma

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
7381	UQCRB	NA		TERPESTACIN	TERPESTACIN	21215626

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