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	GSM4909282	Human	Breast	IDC	1.33e-06	3.57e-01	-0.0288
4521	NUDT1	GSM4909311	Human	Breast	IDC	3.50e-06	-9.78e-02	0.1534
4521	NUDT1	GSM4909312	Human	Breast	IDC	3.60e-03	-5.51e-02	0.1552
4521	NUDT1	GSM4909315	Human	Breast	IDC	5.65e-17	5.94e-01	0.21
4521	NUDT1	GSM4909316	Human	Breast	IDC	4.15e-05	5.02e-01	0.21
4521	NUDT1	GSM4909319	Human	Breast	IDC	3.29e-18	7.71e-02	0.1563
4521	NUDT1	GSM4909321	Human	Breast	IDC	1.91e-04	7.76e-02	0.1559
4521	NUDT1	NCCBC3	Human	Breast	DCIS	1.22e-02	7.81e-02	0.1198
4521	NUDT1	NCCBC5	Human	Breast	DCIS	2.29e-02	1.92e-01	0.2046
4521	NUDT1	P1	Human	Breast	IDC	3.22e-04	-4.50e-02	0.1527
4521	NUDT1	DCIS2	Human	Breast	DCIS	1.05e-19	4.37e-02	0.0085
4521	NUDT1	LZE2D	Human	Esophagus	HGIN	1.97e-04	4.91e-01	0.0642
4521	NUDT1	LZE2T	Human	Esophagus	ESCC	6.36e-05	1.02e+00	0.082
4521	NUDT1	LZE4T	Human	Esophagus	ESCC	1.12e-11	4.20e-01	0.0811
4521	NUDT1	LZE7T	Human	Esophagus	ESCC	2.77e-15	8.12e-01	0.0667
4521	NUDT1	LZE8T	Human	Esophagus	ESCC	6.49e-04	3.60e-01	0.067
4521	NUDT1	LZE20T	Human	Esophagus	ESCC	9.98e-06	3.73e-01	0.0662
4521	NUDT1	LZE22D1	Human	Esophagus	HGIN	1.64e-03	2.63e-01	0.0595
4521	NUDT1	LZE22T	Human	Esophagus	ESCC	5.73e-11	1.07e+00	0.068
4521	NUDT1	LZE24T	Human	Esophagus	ESCC	1.02e-13	5.37e-01	0.0596

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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:004225434	Thyroid	ATC	ribosome biogenesis	203/6293	299/18723	3.63e-34	4.59e-31	203
GO:000636432	Thyroid	ATC	rRNA processing	157/6293	225/18723	9.02e-29	5.70e-26	157
GO:001607232	Thyroid	ATC	rRNA metabolic process	161/6293	236/18723	1.02e-27	5.89e-25	161
GO:000697934	Thyroid	ATC	response to oxidative stress	246/6293	446/18723	2.98e-21	6.09e-19	246
GO:000640127	Thyroid	ATC	RNA catabolic process	165/6293	278/18723	8.45e-19	1.14e-16	165
GO:003447021	Thyroid	ATC	ncRNA processing	216/6293	395/18723	3.14e-18	3.98e-16	216
GO:000640227	Thyroid	ATC	mRNA catabolic process	140/6293	232/18723	5.08e-17	4.65e-15	140
GO:003465525	Thyroid	ATC	nucleobase-containing compound catabolic process	217/6293	407/18723	1.20e-16	1.04e-14	217
GO:004670024	Thyroid	ATC	heterocycle catabolic process	228/6293	445/18723	7.26e-15	4.50e-13	228
GO:004427025	Thyroid	ATC	cellular nitrogen compound catabolic process	229/6293	451/18723	2.25e-14	1.27e-12	229
GO:003466021	Thyroid	ATC	ncRNA metabolic process	240/6293	485/18723	2.03e-13	9.91e-12	240
GO:001943924	Thyroid	ATC	aromatic compound catabolic process	232/6293	467/18723	3.05e-13	1.44e-11	232
GO:005105219	Thyroid	ATC	regulation of DNA metabolic process	183/6293	359/18723	5.97e-12	2.30e-10	183
GO:190136124	Thyroid	ATC	organic cyclic compound catabolic process	238/6293	495/18723	1.12e-11	4.12e-10	238
GO:0071496210	Thyroid	ATC	cellular response to external stimulus	165/6293	320/18723	2.01e-11	7.23e-10	165
GO:200102026	Thyroid	ATC	regulation of response to DNA damage stimulus	121/6293	219/18723	3.22e-11	1.08e-09	121
GO:004578719	Thyroid	ATC	positive regulation of cell cycle	158/6293	313/18723	4.18e-10	1.14e-08	158
GO:000756829	Thyroid	ATC	aging	166/6293	339/18723	2.79e-09	6.60e-08	166
GO:003166827	Thyroid	ATC	cellular response to extracellular stimulus	125/6293	246/18723	1.65e-08	3.31e-07	125
GO:001969328	Thyroid	ATC	ribose phosphate metabolic process	184/6293	396/18723	5.87e-08	1.05e-06	184

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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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