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:000749211	Prostate	Tumor	endoderm development	28/3246	77/18723	5.01e-05	5.55e-04	28
GO:003043312	Prostate	Tumor	ubiquitin-dependent ERAD pathway	30/3246	85/18723	5.26e-05	5.75e-04	30
GO:001095116	Prostate	Tumor	negative regulation of endopeptidase activity	68/3246	252/18723	7.91e-05	8.19e-04	68
GO:003650313	Prostate	Tumor	ERAD pathway	35/3246	107/18723	8.02e-05	8.19e-04	35
GO:001046617	Prostate	Tumor	negative regulation of peptidase activity	70/3246	262/18723	8.76e-05	8.66e-04	70
GO:005127114	Prostate	Tumor	negative regulation of cellular component movement	92/3246	367/18723	1.03e-04	9.99e-04	92
GO:007189714	Prostate	Tumor	DNA biosynthetic process	51/3246	180/18723	1.63e-04	1.46e-03	51
GO:001063917	Prostate	Tumor	negative regulation of organelle organization	87/3246	348/18723	1.73e-04	1.53e-03	87
GO:000736912	Prostate	Tumor	gastrulation	52/3246	185/18723	1.76e-04	1.55e-03	52
GO:000931415	Prostate	Tumor	response to radiation	109/3246	456/18723	1.94e-04	1.70e-03	109
GO:200014614	Prostate	Tumor	negative regulation of cell motility	89/3246	359/18723	1.99e-04	1.74e-03	89
GO:003287215	Prostate	Tumor	regulation of stress-activated MAPK cascade	53/3246	192/18723	2.51e-04	2.11e-03	53
GO:005105212	Prostate	Tumor	regulation of DNA metabolic process	88/3246	359/18723	3.23e-04	2.59e-03	88
GO:000661115	Prostate	Tumor	protein export from nucleus	21/3246	57/18723	3.44e-04	2.73e-03	21
GO:003357413	Prostate	Tumor	response to testosterone	17/3246	42/18723	3.45e-04	2.73e-03	17
GO:004578611	Prostate	Tumor	negative regulation of cell cycle	93/3246	385/18723	3.79e-04	2.95e-03	93
GO:007030215	Prostate	Tumor	regulation of stress-activated protein kinase signaling cascade	53/3246	195/18723	3.80e-04	2.95e-03	53
GO:004001313	Prostate	Tumor	negative regulation of locomotion	94/3246	391/18723	4.20e-04	3.21e-03	94
GO:003033613	Prostate	Tumor	negative regulation of cell migration	84/3246	344/18723	4.95e-04	3.66e-03	84
GO:000170411	Prostate	Tumor	formation of primary germ layer	36/3246	121/18723	5.22e-04	3.82e-03	36

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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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