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: NUDT1

Gene summary for NUDT1

Gene summary.

Gene information	Species	Human
	Gene symbol	NUDT1
	Gene ID	4521
	Gene name	nudix hydrolase 1
	Gene Alias	MTH1
	Cytomap	7p22.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024R819

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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
4521	NUDT1	LN38	Human	Oral cavity	OSCC	3.60e-03	1.34e+00	0.168
4521	NUDT1	LN46	Human	Oral cavity	OSCC	6.09e-26	1.34e+00	0.1666
4521	NUDT1	LP15	Human	Oral cavity	LP	1.51e-09	1.69e+00	0.2174
4521	NUDT1	LP17	Human	Oral cavity	LP	5.33e-07	1.33e+00	0.2349
4521	NUDT1	SYSMH1	Human	Oral cavity	OSCC	1.99e-07	2.89e-01	0.1127
4521	NUDT1	SYSMH2	Human	Oral cavity	OSCC	3.31e-32	1.29e+00	0.2326
4521	NUDT1	SYSMH3	Human	Oral cavity	OSCC	8.85e-37	1.21e+00	0.2442
4521	NUDT1	SYSMH4	Human	Oral cavity	OSCC	3.47e-06	1.86e-01	0.1226
4521	NUDT1	SYSMH5	Human	Oral cavity	OSCC	8.49e-25	8.03e-01	0.0647
4521	NUDT1	SYSMH6	Human	Oral cavity	OSCC	9.76e-04	4.49e-01	0.1275
4521	NUDT1	P4_S8_cSCC	Human	Skin	cSCC	3.70e-05	1.36e-01	-0.3095
4521	NUDT1	P5_S10_cSCC	Human	Skin	cSCC	7.41e-18	4.50e-01	-0.299
4521	NUDT1	P1_cSCC	Human	Skin	cSCC	3.98e-33	1.16e+00	0.0292
4521	NUDT1	P2_cSCC	Human	Skin	cSCC	1.91e-22	8.00e-01	-0.024
4521	NUDT1	P4_cSCC	Human	Skin	cSCC	2.59e-39	1.15e+00	-0.00290000000000005
4521	NUDT1	P10_cSCC	Human	Skin	cSCC	3.77e-28	1.14e+00	0.1017
4521	NUDT1	cSCC_p8	Human	Skin	cSCC	4.44e-05	1.28e-01	-0.1971
4521	NUDT1	cSCC_p9	Human	Skin	cSCC	2.45e-04	1.45e-01	-0.1991
4521	NUDT1	PTC05	Human	Thyroid	PTC	3.72e-10	3.39e-01	0.2065
4521	NUDT1	PTC06	Human	Thyroid	PTC	3.92e-13	3.02e-01	0.2057

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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:000697914	Breast	IDC	response to oxidative stress	83/1434	446/18723	2.36e-14	7.06e-12	83
GO:001003814	Breast	IDC	response to metal ion	65/1434	373/18723	2.95e-10	3.42e-08	65
GO:004668613	Breast	IDC	response to cadmium ion	19/1434	68/18723	4.97e-07	2.45e-05	19
GO:000756813	Breast	IDC	aging	52/1434	339/18723	1.14e-06	5.10e-05	52
GO:004860812	Breast	IDC	reproductive structure development	60/1434	424/18723	2.71e-06	1.03e-04	60
GO:006145813	Breast	IDC	reproductive system development	60/1434	427/18723	3.41e-06	1.24e-04	60
GO:007252114	Breast	IDC	purine-containing compound metabolic process	57/1434	416/18723	1.28e-05	3.31e-04	57
GO:007149614	Breast	IDC	cellular response to external stimulus	45/1434	320/18723	5.40e-05	1.15e-03	45
GO:003166814	Breast	IDC	cellular response to extracellular stimulus	35/1434	246/18723	2.79e-04	4.26e-03	35
GO:0008406	Breast	IDC	gonad development	32/1434	221/18723	3.64e-04	5.23e-03	32
GO:0045137	Breast	IDC	development of primary sexual characteristics	32/1434	227/18723	5.85e-04	7.44e-03	32
GO:200102013	Breast	IDC	regulation of response to DNA damage stimulus	30/1434	219/18723	1.36e-03	1.40e-02	30
GO:190136112	Breast	IDC	organic cyclic compound catabolic process	56/1434	495/18723	2.12e-03	1.99e-02	56
GO:0007548	Breast	IDC	sex differentiation	35/1434	276/18723	2.23e-03	2.07e-02	35
GO:00085841	Breast	IDC	male gonad development	21/1434	141/18723	2.46e-03	2.22e-02	21
GO:004670012	Breast	IDC	heterocycle catabolic process	51/1434	445/18723	2.51e-03	2.25e-02	51
GO:00465461	Breast	IDC	development of primary male sexual characteristics	21/1434	142/18723	2.69e-03	2.39e-02	21
GO:003465513	Breast	IDC	nucleobase-containing compound catabolic process	47/1434	407/18723	3.12e-03	2.63e-02	47
GO:00466611	Breast	IDC	male sex differentiation	23/1434	165/18723	3.74e-03	3.07e-02	23
GO:004427012	Breast	IDC	cellular nitrogen compound catabolic process	50/1434	451/18723	5.29e-03	3.93e-02	50

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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

NUDT1

SNV

Missense_Mutation

rs374666803

c.205N>A

p.Glu69Lys

p.E69K

P36639

protein_coding

tolerated(0.2)

possibly_damaging(0.847)

TCGA-AC-A2B8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

chemo

NUDT1

SNV

Missense_Mutation

rs746490760

c.533N>T

p.Thr178Met

p.T178M

P36639

protein_coding

tolerated(0.08)

benign(0.188)

TCGA-C8-A12V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NUDT1

insertion

Nonsense_Mutation

novel

c.483_484insCCTGCTCTGCGCCCACCCTAAAATGAGAAACACGGTCATGAGGATGAAATA

p.Lys161_Phe162insProAlaLeuArgProProTerAsnGluLysHisGlyHisGluAspGluIle

p.K161_F162insPALRPP*NEKHGHEDEI

P36639

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

NUDT1

SNV

Missense_Mutation

c.190N>C

p.Glu64Gln

p.E64Q

P36639

protein_coding

tolerated(0.43)

benign(0.255)

TCGA-C5-A1M6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NUDT1

SNV

Missense_Mutation

rs747651511

c.373C>T

p.Arg125Cys

p.R125C

P36639

protein_coding

tolerated(0.05)

benign(0.073)

TCGA-AA-A01R-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

5-fluorouracil

NUDT1

SNV

Missense_Mutation

novel

c.421N>T

p.Pro141Ser

p.P141S

P36639

protein_coding

deleterious(0.05)

possibly_damaging(0.834)

TCGA-E6-A1M0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

NUDT1

SNV

Missense_Mutation

novel

c.466N>G

p.Phe156Val

p.F156V

P36639

protein_coding

deleterious(0)

benign(0.436)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NUDT1

SNV

Missense_Mutation

novel

c.124N>A

p.Leu42Ile

p.L42I

P36639

protein_coding

deleterious(0)

possibly_damaging(0.787)

TCGA-EO-A22X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unspecific

Carboplatin

Complete Response

NUDT1

SNV

Missense_Mutation

novel

c.291N>A

p.Phe97Leu

p.F97L

P36639

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-QF-A5YS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

NUDT1

SNV

Missense_Mutation

rs115556911

c.367N>A

p.Glu123Lys

p.E123K

P36639

protein_coding

deleterious(0.03)

probably_damaging(0.999)

TCGA-44-6779-01

Lung

lung adenocarcinoma

Female

<65

I/II

Chemotherapy

taxol

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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
4521	NUDT1	DNA REPAIR, ENZYME		8-oxo-dgtp		26238318

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