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: NUDT5

Gene summary for NUDT5

Gene summary.

Gene information	Species	Human
	Gene symbol	NUDT5
	Gene ID	11164
	Gene name	nudix hydrolase 5
	Gene Alias	YSA1
	Cytomap	10p14
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	Q9UKK9

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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
11164	NUDT5	GSM4909281	Human	Breast	IDC	2.25e-12	3.50e-01	0.21
11164	NUDT5	GSM4909282	Human	Breast	IDC	3.96e-32	6.23e-01	-0.0288
11164	NUDT5	GSM4909285	Human	Breast	IDC	1.56e-64	9.29e-01	0.21
11164	NUDT5	GSM4909290	Human	Breast	IDC	4.02e-03	2.75e-01	0.2096
11164	NUDT5	GSM4909297	Human	Breast	IDC	7.72e-05	-5.59e-02	0.1517
11164	NUDT5	GSM4909311	Human	Breast	IDC	8.65e-10	-1.11e-01	0.1534
11164	NUDT5	GSM4909312	Human	Breast	IDC	5.06e-04	7.90e-02	0.1552
11164	NUDT5	GSM4909319	Human	Breast	IDC	4.44e-13	-5.36e-02	0.1563
11164	NUDT5	GSM4909321	Human	Breast	IDC	2.53e-03	-1.25e-02	0.1559
11164	NUDT5	brca1	Human	Breast	Precancer	1.90e-11	3.42e-01	-0.0338
11164	NUDT5	brca2	Human	Breast	Precancer	5.57e-10	2.70e-01	-0.024
11164	NUDT5	M2	Human	Breast	IDC	1.33e-03	3.94e-01	0.21
11164	NUDT5	P1	Human	Breast	IDC	8.57e-05	-5.81e-02	0.1527
11164	NUDT5	P2	Human	Breast	IDC	5.57e-03	3.02e-01	0.21
11164	NUDT5	DCIS2	Human	Breast	DCIS	1.83e-35	7.09e-02	0.0085
11164	NUDT5	LZE2T	Human	Esophagus	ESCC	3.69e-06	5.74e-01	0.082
11164	NUDT5	LZE4T	Human	Esophagus	ESCC	3.58e-14	6.36e-01	0.0811
11164	NUDT5	LZE5T	Human	Esophagus	ESCC	1.31e-03	6.16e-01	0.0514
11164	NUDT5	LZE7T	Human	Esophagus	ESCC	4.31e-04	4.98e-01	0.0667
11164	NUDT5	LZE8T	Human	Esophagus	ESCC	7.32e-15	4.30e-01	0.067

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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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00196938	Breast	Precancer	ribose phosphate metabolic process	49/1080	396/18723	3.81e-07	1.78e-05	49
GO:00091179	Breast	Precancer	nucleotide metabolic process	56/1080	489/18723	7.40e-07	3.00e-05	56
GO:00067539	Breast	Precancer	nucleoside phosphate metabolic process	56/1080	497/18723	1.24e-06	4.70e-05	56
GO:00091858	Breast	Precancer	ribonucleoside diphosphate metabolic process	20/1080	106/18723	2.37e-06	8.17e-05	20
GO:00091328	Breast	Precancer	nucleoside diphosphate metabolic process	21/1080	124/18723	7.98e-06	2.17e-04	21
GO:00346558	Breast	Precancer	nucleobase-containing compound catabolic process	42/1080	407/18723	1.91e-04	3.06e-03	42
GO:00160527	Breast	Precancer	carbohydrate catabolic process	21/1080	154/18723	2.10e-04	3.28e-03	21
GO:00467007	Breast	Precancer	heterocycle catabolic process	44/1080	445/18723	3.49e-04	4.88e-03	44
GO:00442708	Breast	Precancer	cellular nitrogen compound catabolic process	44/1080	451/18723	4.64e-04	6.12e-03	44
GO:00194397	Breast	Precancer	aromatic compound catabolic process	44/1080	467/18723	9.55e-04	1.07e-02	44
GO:19013617	Breast	Precancer	organic cyclic compound catabolic process	45/1080	495/18723	1.73e-03	1.74e-02	45
GO:00059966	Breast	Precancer	monosaccharide metabolic process	27/1080	257/18723	1.94e-03	1.88e-02	27
GO:004603414	Breast	IDC	ATP metabolic process	85/1434	277/18723	6.42e-30	1.82e-26	85
GO:001969314	Breast	IDC	ribose phosphate metabolic process	58/1434	396/18723	1.31e-06	5.73e-05	58
GO:000675313	Breast	IDC	nucleoside phosphate metabolic process	68/1434	497/18723	2.01e-06	8.23e-05	68
GO:000911713	Breast	IDC	nucleotide metabolic process	67/1434	489/18723	2.28e-06	9.05e-05	67
GO:000913213	Breast	IDC	nucleoside diphosphate metabolic process	23/1434	124/18723	6.08e-05	1.27e-03	23
GO:000918513	Breast	IDC	ribonucleoside diphosphate metabolic process	20/1434	106/18723	1.41e-04	2.49e-03	20
GO:190136112	Breast	IDC	organic cyclic compound catabolic process	56/1434	495/18723	2.12e-03	1.99e-02	56

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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

NUDT5

SNV

Missense_Mutation

c.307N>A

p.Glu103Lys

p.E103K

Q9UKK9

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

NUDT5

insertion

Frame_Shift_Ins

novel

c.202_203insACCCTGCCGTCTCCAGCCTTTTGAGTAATTGCCC

p.Leu68HisfsTer19

p.L68Hfs*19

Q9UKK9

protein_coding

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NUDT5

deletion

Frame_Shift_Del

novel

c.490delG

p.Asp164MetfsTer23

p.D164Mfs*23

Q9UKK9

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

NUDT5

SNV

Missense_Mutation

c.439N>G

p.Thr147Ala

p.T147A

Q9UKK9

protein_coding

tolerated(0.61)

benign(0.017)

TCGA-G4-6588-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

NUDT5

SNV

Missense_Mutation

rs755821025

c.151N>T

p.Arg51Cys

p.R51C

Q9UKK9

protein_coding

deleterious(0)

probably_damaging(0.965)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

NUDT5

SNV

Missense_Mutation

novel

c.611N>G

p.Leu204Arg

p.L204R

Q9UKK9

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NUDT5

SNV

Missense_Mutation

c.472N>A

p.Pro158Thr

p.P158T

Q9UKK9

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

NUDT5

SNV

Missense_Mutation

novel

c.626N>A

p.Ala209Glu

p.A209E

Q9UKK9

protein_coding

tolerated_low_confidence(1)

benign(0)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

NUDT5

SNV

Missense_Mutation

novel

c.116C>T

p.Pro39Leu

p.P39L

Q9UKK9

protein_coding

deleterious(0)

possibly_damaging(0.8)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NUDT5

SNV

Missense_Mutation

rs755821025

c.151N>T

p.Arg51Cys

p.R51C

Q9UKK9

protein_coding

deleterious(0)

probably_damaging(0.965)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

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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

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