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	P5T-E	Human	Esophagus	ESCC	2.37e-19	6.80e-01	0.1327
7398	USP1	P8T-E	Human	Esophagus	ESCC	7.57e-19	5.22e-01	0.0889
7398	USP1	P9T-E	Human	Esophagus	ESCC	6.76e-08	2.62e-01	0.1131
7398	USP1	P10T-E	Human	Esophagus	ESCC	2.07e-38	8.78e-01	0.116
7398	USP1	P11T-E	Human	Esophagus	ESCC	6.42e-10	6.18e-01	0.1426
7398	USP1	P12T-E	Human	Esophagus	ESCC	2.24e-21	4.67e-01	0.1122
7398	USP1	P15T-E	Human	Esophagus	ESCC	5.11e-17	5.81e-01	0.1149
7398	USP1	P16T-E	Human	Esophagus	ESCC	1.15e-19	5.71e-01	0.1153
7398	USP1	P17T-E	Human	Esophagus	ESCC	3.49e-03	5.35e-01	0.1278
7398	USP1	P20T-E	Human	Esophagus	ESCC	7.13e-23	5.22e-01	0.1124
7398	USP1	P21T-E	Human	Esophagus	ESCC	3.13e-39	8.47e-01	0.1617
7398	USP1	P22T-E	Human	Esophagus	ESCC	1.29e-16	2.86e-01	0.1236
7398	USP1	P23T-E	Human	Esophagus	ESCC	1.67e-27	7.09e-01	0.108
7398	USP1	P24T-E	Human	Esophagus	ESCC	1.48e-13	3.41e-01	0.1287
7398	USP1	P26T-E	Human	Esophagus	ESCC	1.24e-30	5.64e-01	0.1276
7398	USP1	P27T-E	Human	Esophagus	ESCC	1.79e-33	7.97e-01	0.1055
7398	USP1	P28T-E	Human	Esophagus	ESCC	1.36e-21	5.84e-01	0.1149
7398	USP1	P30T-E	Human	Esophagus	ESCC	7.76e-17	1.04e+00	0.137
7398	USP1	P31T-E	Human	Esophagus	ESCC	3.85e-36	8.74e-01	0.1251
7398	USP1	P32T-E	Human	Esophagus	ESCC	2.49e-32	9.40e-01	0.1666

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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:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:00458619	Breast	Precancer	negative regulation of proteolysis	50/1080	351/18723	2.99e-09	2.39e-07	50
GO:00513468	Breast	Precancer	negative regulation of hydrolase activity	50/1080	379/18723	3.85e-08	2.34e-06	50
GO:00349769	Breast	Precancer	response to endoplasmic reticulum stress	38/1080	256/18723	7.89e-08	4.60e-06	38
GO:00104668	Breast	Precancer	negative regulation of peptidase activity	38/1080	262/18723	1.46e-07	7.82e-06	38
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:00109519	Breast	Precancer	negative regulation of endopeptidase activity	37/1080	252/18723	1.55e-07	8.05e-06	37
GO:19033629	Breast	Precancer	regulation of cellular protein catabolic process	36/1080	255/18723	6.03e-07	2.55e-05	36
GO:00421769	Breast	Precancer	regulation of protein catabolic process	47/1080	391/18723	1.50e-06	5.58e-05	47
GO:19030509	Breast	Precancer	regulation of proteolysis involved in cellular protein catabolic process	31/1080	221/18723	4.10e-06	1.27e-04	31
GO:00313309	Breast	Precancer	negative regulation of cellular catabolic process	34/1080	262/18723	8.16e-06	2.20e-04	34
GO:19058979	Breast	Precancer	regulation of response to endoplasmic reticulum stress	16/1080	82/18723	1.53e-05	3.75e-04	16
GO:19033638	Breast	Precancer	negative regulation of cellular protein catabolic process	14/1080	75/18723	8.54e-05	1.63e-03	14
GO:00098959	Breast	Precancer	negative regulation of catabolic process	36/1080	320/18723	9.92e-05	1.83e-03	36
GO:19035739	Breast	Precancer	negative regulation of response to endoplasmic reticulum stress	10/1080	44/18723	1.61e-04	2.69e-03	10
GO:00611369	Breast	Precancer	regulation of proteasomal protein catabolic process	24/1080	187/18723	1.99e-04	3.14e-03	24
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:19030518	Breast	Precancer	negative regulation of proteolysis involved in cellular protein catabolic process	12/1080	64/18723	2.58e-04	3.83e-03	12
GO:20000599	Breast	Precancer	negative regulation of ubiquitin-dependent protein catabolic process	10/1080	48/18723	3.43e-04	4.81e-03	10

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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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