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: USP5

Gene summary for USP5

Gene summary.

Gene information	Species	Human
	Gene symbol	USP5
	Gene ID	8078
	Gene name	ubiquitin specific peptidase 5
	Gene Alias	ISOT
	Cytomap	12p13.31
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	A0A140VJZ1

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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
8078	USP5	HTA11_3410_2000001011	Human	Colorectum	AD	9.57e-04	1.56e-01	0.0155
8078	USP5	HTA11_2487_2000001011	Human	Colorectum	SER	5.92e-04	2.68e-01	-0.1808
8078	USP5	HTA11_1938_2000001011	Human	Colorectum	AD	8.81e-10	4.33e-01	-0.0811
8078	USP5	HTA11_347_2000001011	Human	Colorectum	AD	2.10e-05	2.55e-01	-0.1954
8078	USP5	HTA11_411_2000001011	Human	Colorectum	SER	5.24e-03	5.44e-01	-0.2602
8078	USP5	HTA11_696_2000001011	Human	Colorectum	AD	4.25e-14	3.22e-01	-0.1464
8078	USP5	HTA11_866_2000001011	Human	Colorectum	AD	2.71e-08	2.37e-01	-0.1001
8078	USP5	HTA11_1391_2000001011	Human	Colorectum	AD	5.43e-10	4.42e-01	-0.059
8078	USP5	HTA11_6801_2000001011	Human	Colorectum	SER	1.18e-07	4.91e-01	0.0171
8078	USP5	HTA11_7696_3000711011	Human	Colorectum	AD	4.40e-15	4.24e-01	0.0674
8078	USP5	HTA11_6818_2000001021	Human	Colorectum	AD	1.05e-02	2.43e-01	0.0588
8078	USP5	HTA11_99999970781_79442	Human	Colorectum	MSS	2.03e-26	4.74e-01	0.294
8078	USP5	HTA11_99999965062_69753	Human	Colorectum	MSI-H	6.62e-03	9.44e-01	0.3487
8078	USP5	HTA11_99999965104_69814	Human	Colorectum	MSS	1.57e-02	3.03e-01	0.281
8078	USP5	HTA11_99999971662_82457	Human	Colorectum	MSS	8.28e-24	4.91e-01	0.3859
8078	USP5	HTA11_99999974143_84620	Human	Colorectum	MSS	1.50e-08	2.94e-01	0.3005
8078	USP5	LZE4T	Human	Esophagus	ESCC	9.29e-03	1.59e-01	0.0811
8078	USP5	LZE7T	Human	Esophagus	ESCC	4.74e-04	3.83e-01	0.0667
8078	USP5	LZE8T	Human	Esophagus	ESCC	1.12e-08	2.94e-01	0.067
8078	USP5	LZE24T	Human	Esophagus	ESCC	3.28e-05	2.09e-01	0.0596

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:19030522	Colorectum	MSS	positive regulation of proteolysis involved in cellular protein catabolic process	48/3467	133/18723	1.21e-06	4.06e-05	48
GO:20000602	Colorectum	MSS	positive regulation of ubiquitin-dependent protein catabolic process	39/3467	107/18723	8.92e-06	2.19e-04	39
GO:19018002	Colorectum	MSS	positive regulation of proteasomal protein catabolic process	40/3467	114/18723	1.96e-05	4.19e-04	40
GO:00709972	Colorectum	MSS	neuron death	97/3467	361/18723	5.21e-05	9.31e-04	97
GO:00324362	Colorectum	MSS	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	32/3467	90/18723	9.56e-05	1.50e-03	32
GO:00514022	Colorectum	MSS	neuron apoptotic process	66/3467	246/18723	7.94e-04	8.36e-03	66
GO:0071108	Colorectum	MSS	protein K48-linked deubiquitination	13/3467	35/18723	7.38e-03	4.68e-02	13
GO:00421763	Colorectum	MSI-H	regulation of protein catabolic process	65/1319	391/18723	6.96e-11	1.29e-08	65
GO:19033623	Colorectum	MSI-H	regulation of cellular protein catabolic process	49/1319	255/18723	9.82e-11	1.66e-08	49
GO:19030503	Colorectum	MSI-H	regulation of proteolysis involved in cellular protein catabolic process	43/1319	221/18723	9.16e-10	1.27e-07	43
GO:00104983	Colorectum	MSI-H	proteasomal protein catabolic process	71/1319	490/18723	4.67e-09	6.03e-07	71
GO:20000583	Colorectum	MSI-H	regulation of ubiquitin-dependent protein catabolic process	34/1319	164/18723	9.82e-09	1.21e-06	34
GO:00611363	Colorectum	MSI-H	regulation of proteasomal protein catabolic process	34/1319	187/18723	2.84e-07	2.25e-05	34
GO:00098963	Colorectum	MSI-H	positive regulation of catabolic process	64/1319	492/18723	1.39e-06	9.16e-05	64
GO:00324343	Colorectum	MSI-H	regulation of proteasomal ubiquitin-dependent protein catabolic process	26/1319	134/18723	1.98e-06	1.25e-04	26
GO:00313313	Colorectum	MSI-H	positive regulation of cellular catabolic process	56/1319	427/18723	4.89e-06	2.54e-04	56
GO:00431613	Colorectum	MSI-H	proteasome-mediated ubiquitin-dependent protein catabolic process	53/1319	412/18723	1.51e-05	6.62e-04	53
GO:00458623	Colorectum	MSI-H	positive regulation of proteolysis	49/1319	372/18723	1.67e-05	7.15e-04	49
GO:00457323	Colorectum	MSI-H	positive regulation of protein catabolic process	34/1319	231/18723	3.46e-05	1.33e-03	34
GO:19033643	Colorectum	MSI-H	positive regulation of cellular protein catabolic process	25/1319	155/18723	8.26e-05	2.72e-03	25

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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

USP5

SNV

Missense_Mutation

c.103N>A

p.Asp35Asn

p.D35N

P45974

protein_coding

deleterious(0.01)

benign(0.124)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP5

SNV

Missense_Mutation

c.891N>C

p.Glu297Asp

p.E297D

P45974

protein_coding

tolerated(0.09)

benign(0.031)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP5

SNV

Missense_Mutation

rs782807103

c.221G>A

p.Arg74Gln

p.R74Q

P45974

protein_coding

tolerated(0.08)

benign(0.001)

TCGA-AN-A0G0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

USP5

SNV

Missense_Mutation

c.1725N>T

p.Lys575Asn

p.K575N

P45974

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-BH-A0B4-01

Breast

breast invasive carcinoma

Male

>=65

III/IV

Hormone Therapy

tamoxiphen

USP5

SNV

Missense_Mutation

novel

c.334N>C

p.Glu112Gln

p.E112Q

P45974

protein_coding

tolerated(0.37)

possibly_damaging(0.672)

TCGA-BH-A8FZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

USP5

insertion

Frame_Shift_Ins

novel

c.339_340insGAAACCAGCCTGGGCAATATGGCAAGACCTCATC

p.Phe114GlufsTer13

p.F114Efs*13

P45974

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP5

insertion

Nonsense_Mutation

novel

c.480_481insCCATTCTGACCTCCTATTGGACTCAGTTTCTTTTTTTCACCTACT

p.Ala160_Ser161insProPheTerProProIleGlyLeuSerPhePhePheSerProThr

p.A160_S161insPF*PPIGLSFFFSPT

P45974

protein_coding

TCGA-A8-A08Z-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

USP5

deletion

Frame_Shift_Del

novel

c.851_852delNN

p.Leu284GlnfsTer11

p.L284Qfs*11

P45974

protein_coding

TCGA-E9-A1RH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

USP5

deletion

Frame_Shift_Del

c.1931delN

p.Pro645LeufsTer45

p.P645Lfs*45

P45974

protein_coding

TCGA-E9-A226-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

USP5

SNV

Missense_Mutation

novel

c.907N>T

p.Arg303Trp

p.R303W

P45974

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
8078	USP5	ENZYME, PROTEASE		VIALININ A	VIALININ A	23791076
8078	USP5	ENZYME, PROTEASE	inhibitor	252166869

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