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: USP1

Gene summary for USP1

Gene summary.

Gene information	Species	Human
	Gene symbol	USP1
	Gene ID	7398
	Gene name	ubiquitin specific peptidase 1
	Gene Alias	UBP
	Cytomap	1p31.3
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	O94782

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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
7398	USP1	GSM4909281	Human	Breast	IDC	1.99e-15	5.59e-01	0.21
7398	USP1	GSM4909282	Human	Breast	IDC	6.34e-11	4.95e-01	-0.0288
7398	USP1	GSM4909285	Human	Breast	IDC	4.08e-19	4.50e-01	0.21
7398	USP1	GSM4909286	Human	Breast	IDC	1.90e-11	4.78e-01	0.1081
7398	USP1	GSM4909287	Human	Breast	IDC	3.37e-10	5.37e-01	0.2057
7398	USP1	GSM4909293	Human	Breast	IDC	4.70e-02	1.68e-01	0.1581
7398	USP1	GSM4909311	Human	Breast	IDC	1.09e-07	-1.44e-01	0.1534
7398	USP1	GSM4909319	Human	Breast	IDC	2.99e-09	-6.62e-02	0.1563
7398	USP1	DCIS2	Human	Breast	DCIS	9.40e-42	2.07e-01	0.0085
7398	USP1	LZE2D	Human	Esophagus	HGIN	8.33e-05	2.54e-01	0.0642
7398	USP1	LZE2T	Human	Esophagus	ESCC	2.09e-06	7.14e-01	0.082
7398	USP1	LZE3D	Human	Esophagus	HGIN	1.74e-02	4.99e-01	0.0668
7398	USP1	LZE4T	Human	Esophagus	ESCC	1.36e-06	2.61e-01	0.0811
7398	USP1	LZE7T	Human	Esophagus	ESCC	3.96e-10	6.55e-01	0.0667
7398	USP1	LZE20T	Human	Esophagus	ESCC	2.62e-04	2.01e-01	0.0662
7398	USP1	LZE24T	Human	Esophagus	ESCC	9.63e-18	5.05e-01	0.0596
7398	USP1	LZE6T	Human	Esophagus	ESCC	4.43e-05	2.03e-01	0.0845
7398	USP1	P1T-E	Human	Esophagus	ESCC	5.22e-03	4.35e-01	0.0875
7398	USP1	P2T-E	Human	Esophagus	ESCC	1.80e-51	1.17e+00	0.1177
7398	USP1	P4T-E	Human	Esophagus	ESCC	2.36e-16	6.02e-01	0.1323

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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
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:2000058113	Thyroid	PTC	regulation of ubiquitin-dependent protein catabolic process	110/5968	164/18723	1.83e-20	2.97e-18	110
GO:0061136113	Thyroid	PTC	regulation of proteasomal protein catabolic process	121/5968	187/18723	2.25e-20	3.37e-18	121
GO:0006979113	Thyroid	PTC	response to oxidative stress	234/5968	446/18723	6.97e-20	9.77e-18	234
GO:0032434113	Thyroid	PTC	regulation of proteasomal ubiquitin-dependent protein catabolic process	94/5968	134/18723	9.17e-20	1.23e-17	94
GO:001657010	Thyroid	PTC	histone modification	235/5968	463/18723	1.17e-17	1.15e-15	235
GO:0006417113	Thyroid	PTC	regulation of translation	236/5968	468/18723	2.70e-17	2.52e-15	236
GO:0010506110	Thyroid	PTC	regulation of autophagy	172/5968	317/18723	8.76e-17	7.57e-15	172
GO:0010563113	Thyroid	PTC	negative regulation of phosphorus metabolic process	219/5968	442/18723	4.47e-15	3.07e-13	219
GO:0045936113	Thyroid	PTC	negative regulation of phosphate metabolic process	218/5968	441/18723	7.08e-15	4.75e-13	218
GO:0034250113	Thyroid	PTC	positive regulation of cellular amide metabolic process	98/5968	162/18723	5.26e-14	3.04e-12	98
GO:00365038	Thyroid	PTC	ERAD pathway	71/5968	107/18723	2.37e-13	1.22e-11	71
GO:0001933113	Thyroid	PTC	negative regulation of protein phosphorylation	173/5968	342/18723	3.46e-13	1.75e-11	173
GO:0045727113	Thyroid	PTC	positive regulation of translation	84/5968	136/18723	6.52e-13	3.08e-11	84
GO:0042326113	Thyroid	PTC	negative regulation of phosphorylation	189/5968	385/18723	1.00e-12	4.64e-11	189
GO:003043315	Thyroid	PTC	ubiquitin-dependent ERAD pathway	59/5968	85/18723	1.30e-12	5.91e-11	59
GO:0000302113	Thyroid	PTC	response to reactive oxygen species	121/5968	222/18723	2.10e-12	9.26e-11	121
GO:0042542113	Thyroid	PTC	response to hydrogen peroxide	86/5968	146/18723	1.39e-11	5.60e-10	86
GO:0051348113	Thyroid	PTC	negative regulation of transferase activity	137/5968	268/18723	3.78e-11	1.36e-09	137
GO:000734619	Thyroid	PTC	regulation of mitotic cell cycle	212/5968	457/18723	4.03e-11	1.44e-09	212
GO:0072331113	Thyroid	PTC	signal transduction by p53 class mediator	92/5968	163/18723	7.29e-11	2.54e-09	92

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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

USP1

SNV

Missense_Mutation

c.1516N>A

p.Cys506Ser

p.C506S

O94782

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A04U-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

USP1

SNV

Missense_Mutation

c.1058N>T

p.Ser353Phe

p.S353F

O94782

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

USP1

SNV

Missense_Mutation

novel

c.127C>G

p.Gln43Glu

p.Q43E

O94782

protein_coding

tolerated(0.18)

benign(0.104)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

USP1

SNV

Missense_Mutation

rs772351967

c.962N>G

p.Tyr321Cys

p.Y321C

O94782

protein_coding

tolerated(0.19)

benign(0)

TCGA-AC-A8OR-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

USP1

SNV

Missense_Mutation

c.670N>G

p.Lys224Glu

p.K224E

O94782

protein_coding

tolerated(0.82)

benign(0.033)

TCGA-AN-A0AL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

USP1

SNV

Missense_Mutation

c.1881N>T

p.Leu627Phe

p.L627F

O94782

protein_coding

deleterious(0.04)

benign(0.376)

TCGA-BH-A0C0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

USP1

SNV

Missense_Mutation

novel

c.219G>C

p.Lys73Asn

p.K73N

O94782

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-BH-A0DX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

USP1

insertion

In_Frame_Ins

novel

c.395_396insCGTTACTTCCAA

p.Asp131_Lys132insAsnValThrSer

p.D131_K132insNVTS

O94782

protein_coding

TCGA-AR-A0TU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Doxorubicin

USP1

insertion

Frame_Shift_Ins

novel

c.2072_2073insCTGCAGGTGCCCACCACCACGCCCGGCTAATTTTTTGTATTTT

p.Ser692CysfsTer15

p.S692Cfs*15

O94782

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

USP1

SNV

Missense_Mutation

novel

c.748G>A

p.Glu250Lys

p.E250K

O94782

protein_coding

tolerated(0.21)

benign(0.341)

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
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		GNF-PF-5510	CHEMBL578741
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		CLOFENOXYDE	CLOFENOXYDE
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		GW7074	CHEMBL72365
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		CETRIMIDE	CETRIMIDE
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		BENZIODARONE	BENZIODARONE
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		GNF-PF-4579	CHEMBL584626
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		AMYLMETACRESOL	AMYLMETACRESOL
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		DIHYDROGAMBOGIC ACID	DIHYDROGAMBOGIC ACID
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		BEXAROTENE	BEXAROTENE
7398	USP1	DNA REPAIR, PROTEASE, ENZYME		DITHIAZANINE	DITHIAZANINE

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