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:00434132	Liver	HCC	macromolecule glycosylation	122/7958	226/18723	3.11e-04	2.21e-03	122
GO:00093941	Liver	HCC	2'-deoxyribonucleotide metabolic process	28/7958	40/18723	4.01e-04	2.71e-03	28
GO:00700852	Liver	HCC	glycosylation	128/7958	240/18723	4.35e-04	2.92e-03	128
GO:00196921	Liver	HCC	deoxyribose phosphate metabolic process	29/7958	42/18723	4.57e-04	3.04e-03	29
GO:00062824	Liver	HCC	regulation of DNA repair	74/7958	130/18723	6.27e-04	3.89e-03	74
GO:00900683	Liver	HCC	positive regulation of cell cycle process	125/7958	236/18723	7.21e-04	4.40e-03	125
GO:00092003	Liver	HCC	deoxyribonucleoside triphosphate metabolic process	14/7958	17/18723	9.39e-04	5.47e-03	14
GO:00063021	Liver	HCC	double-strand break repair	131/7958	251/18723	1.17e-03	6.54e-03	131
GO:19012921	Liver	HCC	nucleoside phosphate catabolic process	49/7958	83/18723	1.73e-03	9.02e-03	49
GO:0009100	Liver	HCC	glycoprotein metabolic process	193/7958	387/18723	1.89e-03	9.62e-03	193
GO:00092641	Liver	HCC	deoxyribonucleotide catabolic process	21/7958	30/18723	2.15e-03	1.08e-02	21
GO:00091661	Liver	HCC	nucleotide catabolic process	43/7958	73/18723	3.43e-03	1.55e-02	43
GO:00463861	Liver	HCC	deoxyribose phosphate catabolic process	21/7958	31/18723	4.01e-03	1.76e-02	21
GO:00714662	Liver	HCC	cellular response to xenobiotic stimulus	93/7958	177/18723	4.35e-03	1.89e-02	93
GO:00091161	Liver	HCC	nucleoside metabolic process	37/7958	62/18723	4.73e-03	2.02e-02	37
GO:006145811	Liver	HCC	reproductive system development	205/7958	427/18723	1.16e-02	4.27e-02	205
GO:2000779	Liver	HCC	regulation of double-strand break repair	47/7958	85/18723	1.17e-02	4.28e-02	47
GO:002261320	Oral cavity	OSCC	ribonucleoprotein complex biogenesis	333/7305	463/18723	8.28e-48	5.24e-44	333
GO:004225420	Oral cavity	OSCC	ribosome biogenesis	230/7305	299/18723	3.22e-41	6.80e-38	230
GO:001049820	Oral cavity	OSCC	proteasomal protein catabolic process	336/7305	490/18723	5.45e-41	8.63e-38	336

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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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