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: UQCR10

Gene summary for UQCR10

Gene summary.

Gene information	Species	Human
	Gene symbol	UQCR10
	Gene ID	29796
	Gene name	ubiquinol-cytochrome c reductase, complex III subunit X
	Gene Alias	HSPC051
	Cytomap	22q12.2
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	Q9UDW1

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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
29796	UQCR10	GSM4909281	Human	Breast	IDC	1.96e-75	7.90e-01	0.21
29796	UQCR10	GSM4909282	Human	Breast	IDC	5.60e-24	4.20e-01	-0.0288
29796	UQCR10	GSM4909287	Human	Breast	IDC	4.78e-18	4.30e-01	0.2057
29796	UQCR10	GSM4909289	Human	Breast	IDC	4.98e-04	4.28e-01	0.1064
29796	UQCR10	GSM4909290	Human	Breast	IDC	9.67e-11	4.11e-01	0.2096
29796	UQCR10	GSM4909291	Human	Breast	IDC	1.70e-87	1.04e+00	0.1753
29796	UQCR10	GSM4909293	Human	Breast	IDC	1.67e-15	4.16e-01	0.1581
29796	UQCR10	GSM4909294	Human	Breast	IDC	1.69e-72	7.18e-01	0.2022
29796	UQCR10	GSM4909296	Human	Breast	IDC	3.97e-35	4.15e-01	0.1524
29796	UQCR10	GSM4909297	Human	Breast	IDC	1.90e-27	2.50e-02	0.1517
29796	UQCR10	GSM4909298	Human	Breast	IDC	6.99e-45	6.43e-01	0.1551
29796	UQCR10	GSM4909301	Human	Breast	IDC	2.51e-06	2.29e-01	0.1577
29796	UQCR10	GSM4909304	Human	Breast	IDC	4.91e-46	6.52e-01	0.1636
29796	UQCR10	GSM4909306	Human	Breast	IDC	1.42e-25	5.11e-01	0.1564
29796	UQCR10	GSM4909307	Human	Breast	IDC	3.38e-02	2.09e-01	0.1569
29796	UQCR10	GSM4909309	Human	Breast	IDC	3.11e-02	3.18e-02	0.0483
29796	UQCR10	GSM4909311	Human	Breast	IDC	1.37e-61	1.20e-01	0.1534
29796	UQCR10	GSM4909312	Human	Breast	IDC	3.37e-22	2.06e-01	0.1552
29796	UQCR10	GSM4909313	Human	Breast	IDC	2.27e-03	-2.28e-02	0.0391
29796	UQCR10	GSM4909315	Human	Breast	IDC	5.68e-68	7.84e-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
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:002290020	Esophagus	HGIN	electron transport chain	66/2587	175/18723	2.21e-15	4.73e-13	66
GO:190260017	Esophagus	HGIN	proton transmembrane transport	43/2587	157/18723	5.51e-06	1.75e-04	43
GO:000612219	Esophagus	HGIN	mitochondrial electron transport, ubiquinol to cytochrome c	7/2587	11/18723	1.89e-04	3.52e-03	7
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0045333110	Esophagus	ESCC	cellular respiration	173/8552	230/18723	4.53e-20	5.99e-18	173
GO:0009060110	Esophagus	ESCC	aerobic respiration	145/8552	189/18723	2.16e-18	2.21e-16	145
GO:0015980110	Esophagus	ESCC	energy derivation by oxidation of organic compounds	220/8552	318/18723	1.20e-17	1.09e-15	220
GO:0022900110	Esophagus	ESCC	electron transport chain	133/8552	175/18723	2.18e-16	1.67e-14	133
GO:0046034111	Esophagus	ESCC	ATP metabolic process	189/8552	277/18723	1.99e-14	1.04e-12	189
GO:0006119111	Esophagus	ESCC	oxidative phosphorylation	106/8552	141/18723	8.19e-13	3.63e-11	106
GO:0022904110	Esophagus	ESCC	respiratory electron transport chain	89/8552	114/18723	1.36e-12	5.80e-11	89
GO:0042773110	Esophagus	ESCC	ATP synthesis coupled electron transport	74/8552	95/18723	1.28e-10	3.77e-09	74
GO:0042775110	Esophagus	ESCC	mitochondrial ATP synthesis coupled electron transport	74/8552	95/18723	1.28e-10	3.77e-09	74
GO:0019646110	Esophagus	ESCC	aerobic electron transport chain	67/8552	87/18723	2.30e-09	5.14e-08	67
GO:0006122110	Esophagus	ESCC	mitochondrial electron transport, ubiquinol to cytochrome c	10/8552	11/18723	2.54e-03	1.08e-02	10
GO:190260018	Esophagus	ESCC	proton transmembrane transport	88/8552	157/18723	5.62e-03	2.10e-02	88
GO:000609112	Liver	Cirrhotic	generation of precursor metabolites and energy	238/4634	490/18723	6.85e-31	1.07e-27	238
GO:002290012	Liver	Cirrhotic	electron transport chain	111/4634	175/18723	1.94e-27	1.52e-24	111
GO:004603412	Liver	Cirrhotic	ATP metabolic process	144/4634	277/18723	1.04e-22	5.02e-20	144
GO:00427737	Liver	Cirrhotic	ATP synthesis coupled electron transport	69/4634	95/18723	1.12e-22	5.02e-20	69

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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

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

UQCR10

SNV

Missense_Mutation

rs374152934

c.109N>A

p.Asp37Asn

p.D37N

Q9UDW1

protein_coding

tolerated(0.06)

probably_damaging(0.977)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

UQCR10

insertion

In_Frame_Ins

novel

c.108_109insAGAGGAACTACAAATCCCATAAAGTGTTGCACGTCTAGGGCCTTTGGA

p.Phe36_Asp37insArgGlyThrThrAsnProIleLysCysCysThrSerArgAlaPheGly

p.F36_D37insRGTTNPIKCCTSRAFG

Q9UDW1

protein_coding

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

UQCR10

SNV

Missense_Mutation

c.97N>A

p.Glu33Lys

p.E33K

Q9UDW1

protein_coding

deleterious(0.03)

probably_damaging(0.951)

TCGA-D5-5541-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

calcium

UQCR10

SNV

Missense_Mutation

novel

c.183N>T

p.Glu61Asp

p.E61D

Q9UDW1

protein_coding

deleterious(0.01)

probably_damaging(0.972)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

UQCR10

SNV

Missense_Mutation

rs536988546

c.64G>A

p.Ala22Thr

p.A22T

Q9UDW1

protein_coding

tolerated(0.21)

benign(0.297)

TCGA-AX-A1C8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unspecific

Carboplatin

UQCR10

SNV

Missense_Mutation

novel

c.158G>T

p.Trp53Leu

p.W53L

Q9UDW1

protein_coding

deleterious(0)

possibly_damaging(0.886)

TCGA-DF-A2KU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

UQCR10

SNV

Missense_Mutation

rs749721393

c.103N>A

p.Ala35Thr

p.A35T

Q9UDW1

protein_coding

tolerated(0.16)

benign(0.015)

TCGA-22-1012-01

Lung

lung squamous cell 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
29796	UQCR10	NA		FAMOXADONE	FAMOXADONE	10843216

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