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:0006163112	Skin	cSCC	purine nucleotide metabolic process	140/4864	396/18723	1.93e-05	2.27e-04	140
GO:006145825	Skin	cSCC	reproductive system development	149/4864	427/18723	2.30e-05	2.65e-04	149
GO:004860824	Skin	cSCC	reproductive structure development	148/4864	424/18723	2.40e-05	2.74e-04	148
GO:001003829	Skin	cSCC	response to metal ion	132/4864	373/18723	3.11e-05	3.42e-04	132
GO:001819610	Skin	cSCC	peptidyl-asparagine modification	16/4864	24/18723	3.35e-05	3.66e-04	16
GO:004668624	Skin	cSCC	response to cadmium ion	32/4864	68/18723	1.44e-04	1.29e-03	32
GO:00063025	Skin	cSCC	double-strand break repair	89/4864	251/18723	5.23e-04	3.92e-03	89
GO:00092625	Skin	cSCC	deoxyribonucleotide metabolic process	22/4864	44/18723	5.41e-04	4.01e-03	22
GO:0009410110	Skin	cSCC	response to xenobiotic stimulus	151/4864	462/18723	6.76e-04	4.82e-03	151
GO:00196925	Skin	cSCC	deoxyribose phosphate metabolic process	21/4864	42/18723	7.20e-04	5.05e-03	21
GO:19016575	Skin	cSCC	glycosyl compound metabolic process	37/4864	88/18723	7.39e-04	5.15e-03	37
GO:00091164	Skin	cSCC	nucleoside metabolic process	27/4864	62/18723	1.99e-03	1.19e-02	27
GO:00093945	Skin	cSCC	2'-deoxyribonucleotide metabolic process	19/4864	40/18723	2.73e-03	1.54e-02	19
GO:00085845	Skin	cSCC	male gonad development	51/4864	141/18723	4.70e-03	2.40e-02	51
GO:00465465	Skin	cSCC	development of primary male sexual characteristics	51/4864	142/18723	5.52e-03	2.73e-02	51
GO:00062827	Skin	cSCC	regulation of DNA repair	47/4864	130/18723	6.52e-03	3.17e-02	47
GO:200102122	Skin	cSCC	negative regulation of response to DNA damage stimulus	31/4864	81/18723	1.00e-02	4.40e-02	31
GO:0022613113	Thyroid	PTC	ribonucleoprotein complex biogenesis	292/5968	463/18723	3.24e-44	2.05e-40	292
GO:0042254113	Thyroid	PTC	ribosome biogenesis	202/5968	299/18723	3.47e-37	5.47e-34	202
GO:0006364112	Thyroid	PTC	rRNA processing	156/5968	225/18723	5.58e-31	5.03e-28	156

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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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