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: USP47

Gene summary for USP47

Gene summary.

Gene information	Species	Human
	Gene symbol	USP47
	Gene ID	55031
	Gene name	ubiquitin specific peptidase 47
	Gene Alias	TRFP
	Cytomap	11p15.3
	Gene Type	protein-coding
	GO ID	GO:0000086
	UniProtAcc	Q68D97

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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
55031	USP47	CCI_2	Human	Cervix	CC	5.49e-03	5.13e-01	0.5249
55031	USP47	CCI_3	Human	Cervix	CC	1.60e-03	5.47e-01	0.516
55031	USP47	HTA11_3410_2000001011	Human	Colorectum	AD	7.18e-16	-6.56e-01	0.0155
55031	USP47	HTA11_2487_2000001011	Human	Colorectum	SER	3.48e-03	-5.42e-01	-0.1808
55031	USP47	HTA11_3361_2000001011	Human	Colorectum	AD	2.20e-08	-7.41e-01	-0.1207
55031	USP47	HTA11_696_2000001011	Human	Colorectum	AD	7.07e-18	-5.53e-01	-0.1464
55031	USP47	HTA11_866_2000001011	Human	Colorectum	AD	9.10e-15	-4.79e-01	-0.1001
55031	USP47	HTA11_1391_2000001011	Human	Colorectum	AD	1.35e-02	-4.22e-01	-0.059
55031	USP47	HTA11_5212_2000001011	Human	Colorectum	AD	5.25e-03	-7.51e-01	-0.2061
55031	USP47	HTA11_546_2000001011	Human	Colorectum	AD	2.27e-02	-4.79e-01	-0.0842
55031	USP47	HTA11_866_3004761011	Human	Colorectum	AD	2.98e-12	-6.71e-01	0.096
55031	USP47	HTA11_8622_2000001021	Human	Colorectum	SER	1.83e-02	-6.95e-01	0.0528
55031	USP47	HTA11_10711_2000001011	Human	Colorectum	AD	9.32e-07	-6.27e-01	0.0338
55031	USP47	HTA11_7696_3000711011	Human	Colorectum	AD	2.14e-21	-5.54e-01	0.0674
55031	USP47	HTA11_6818_2000001021	Human	Colorectum	AD	3.64e-04	-6.33e-01	0.0588
55031	USP47	HTA11_99999970781_79442	Human	Colorectum	MSS	6.31e-06	-3.74e-01	0.294
55031	USP47	HTA11_99999971662_82457	Human	Colorectum	MSS	1.52e-09	-4.39e-01	0.3859
55031	USP47	HTA11_99999973899_84307	Human	Colorectum	MSS	5.62e-05	-6.66e-01	0.2585
55031	USP47	HTA11_99999974143_84620	Human	Colorectum	MSS	1.58e-25	-6.47e-01	0.3005
55031	USP47	A015-C-203	Human	Colorectum	FAP	6.69e-28	-2.14e-01	-0.1294

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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
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:009719310	Cervix	CC	intrinsic apoptotic signaling pathway	85/2311	288/18723	4.56e-15	6.46e-12	85
GO:200123310	Cervix	CC	regulation of apoptotic signaling pathway	96/2311	356/18723	4.08e-14	3.05e-11	96
GO:005254710	Cervix	CC	regulation of peptidase activity	112/2311	461/18723	6.70e-13	3.08e-10	112
GO:005254810	Cervix	CC	regulation of endopeptidase activity	103/2311	432/18723	1.89e-11	5.14e-09	103
GO:200124210	Cervix	CC	regulation of intrinsic apoptotic signaling pathway	52/2311	164/18723	5.06e-11	1.01e-08	52
GO:00160557	Cervix	CC	Wnt signaling pathway	98/2311	444/18723	4.82e-09	4.65e-07	98
GO:01987387	Cervix	CC	cell-cell signaling by wnt	98/2311	446/18723	6.16e-09	5.58e-07	98
GO:200011610	Cervix	CC	regulation of cysteine-type endopeptidase activity	61/2311	235/18723	8.69e-09	7.22e-07	61
GO:004328110	Cervix	CC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	55/2311	209/18723	2.77e-08	1.95e-06	55
GO:004586110	Cervix	CC	negative regulation of proteolysis	80/2311	351/18723	2.88e-08	1.98e-06	80
GO:00301117	Cervix	CC	regulation of Wnt signaling pathway	76/2311	328/18723	3.05e-08	2.08e-06	76
GO:200123410	Cervix	CC	negative regulation of apoptotic signaling pathway	56/2311	224/18723	1.39e-07	6.70e-06	56
GO:00447725	Cervix	CC	mitotic cell cycle phase transition	89/2311	424/18723	2.70e-07	1.12e-05	89
GO:00513469	Cervix	CC	negative regulation of hydrolase activity	81/2311	379/18723	4.27e-07	1.67e-05	81
GO:00104669	Cervix	CC	negative regulation of peptidase activity	60/2311	262/18723	1.27e-06	4.34e-05	60
GO:00608287	Cervix	CC	regulation of canonical Wnt signaling pathway	58/2311	253/18723	1.83e-06	5.89e-05	58
GO:00600707	Cervix	CC	canonical Wnt signaling pathway	66/2311	303/18723	2.47e-06	7.35e-05	66
GO:00712148	Cervix	CC	cellular response to abiotic stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:01040048	Cervix	CC	cellular response to environmental stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:001095110	Cervix	CC	negative regulation of endopeptidase activity	56/2311	252/18723	7.43e-06	1.74e-04	56

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

USP47

SNV

Missense_Mutation

rs777625787

c.1180N>A

p.Asp394Asn

p.D394N

Q96K76

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-EO-A3AV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

USP47

SNV

Missense_Mutation

novel

c.2100N>C

p.Arg700Ser

p.R700S

Q96K76

protein_coding

deleterious(0)

benign(0.093)

TCGA-EO-A3B0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

USP47

SNV

Missense_Mutation

novel

c.3176N>T

p.Arg1059Ile

p.R1059I

Q96K76

protein_coding

deleterious(0)

benign(0.276)

TCGA-EO-A3B0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

USP47

SNV

Missense_Mutation

novel

c.3359N>C

p.Lys1120Thr

p.K1120T

Q96K76

protein_coding

deleterious(0.01)

probably_damaging(0.954)

TCGA-EO-A3B0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

USP47

SNV

Missense_Mutation

novel

c.2338A>C

p.Thr780Pro

p.T780P

Q96K76

protein_coding

tolerated(0.09)

possibly_damaging(0.852)

TCGA-EO-A3KX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

USP47

SNV

Missense_Mutation

novel

c.1422N>T

p.Lys474Asn

p.K474N

Q96K76

protein_coding

deleterious(0.02)

benign(0.009)

TCGA-EY-A1GI-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

USP47

SNV

Missense_Mutation

rs545063837

c.2297N>A

p.Arg766His

p.R766H

Q96K76

protein_coding

deleterious(0)

possibly_damaging(0.851)

TCGA-EY-A215-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

USP47

SNV

Missense_Mutation

novel

c.34A>G

p.Lys12Glu

p.K12E

Q96K76

protein_coding

tolerated_low_confidence(0.53)

benign(0.017)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

USP47

SNV

Missense_Mutation

novel

c.82N>G

p.Lys28Glu

p.K28E

Q96K76

protein_coding

deleterious_low_confidence(0.03)

possibly_damaging(0.899)

TCGA-FI-A2F4-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

USP47

SNV

Missense_Mutation

novel

c.1169N>C

p.Leu390Pro

p.L390P

Q96K76

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-FI-A2F4-01

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

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