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: NUDT8

Gene summary for NUDT8

Gene summary.

Gene information	Species	Human
	Gene symbol	NUDT8
	Gene ID	254552
	Gene name	nudix hydrolase 8
	Gene Alias	NUDT8
	Cytomap	11q13.2
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	Q8WV74

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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
254552	NUDT8	GSM4909282	Human	Breast	IDC	2.77e-07	4.14e-01	-0.0288
254552	NUDT8	GSM4909290	Human	Breast	IDC	5.31e-43	1.03e+00	0.2096
254552	NUDT8	GSM4909294	Human	Breast	IDC	7.39e-17	7.04e-01	0.2022
254552	NUDT8	GSM4909296	Human	Breast	IDC	2.05e-02	-6.05e-02	0.1524
254552	NUDT8	GSM4909297	Human	Breast	IDC	2.25e-03	-9.53e-02	0.1517
254552	NUDT8	GSM4909311	Human	Breast	IDC	1.38e-04	-9.11e-02	0.1534
254552	NUDT8	GSM4909312	Human	Breast	IDC	1.69e-02	-2.53e-02	0.1552
254552	NUDT8	GSM4909315	Human	Breast	IDC	6.96e-19	6.61e-01	0.21
254552	NUDT8	GSM4909316	Human	Breast	IDC	7.65e-05	4.49e-01	0.21
254552	NUDT8	GSM4909319	Human	Breast	IDC	6.19e-10	-3.63e-02	0.1563
254552	NUDT8	GSM4909321	Human	Breast	IDC	1.89e-03	-3.68e-02	0.1559
254552	NUDT8	NCCBC6	Human	Breast	DCIS	1.48e-24	1.30e+00	0.2095
254552	NUDT8	DCIS2	Human	Breast	DCIS	1.16e-14	5.65e-02	0.0085
254552	NUDT8	LZE4T	Human	Esophagus	ESCC	4.06e-06	1.13e-01	0.0811
254552	NUDT8	LZE20T	Human	Esophagus	ESCC	7.57e-24	7.62e-01	0.0662
254552	NUDT8	LZE22D1	Human	Esophagus	HGIN	1.39e-07	4.50e-01	0.0595
254552	NUDT8	LZE22T	Human	Esophagus	ESCC	3.60e-08	6.14e-01	0.068
254552	NUDT8	LZE24T	Human	Esophagus	ESCC	2.76e-13	4.40e-01	0.0596
254552	NUDT8	LZE21T	Human	Esophagus	ESCC	8.25e-07	3.48e-01	0.0655
254552	NUDT8	P1T-E	Human	Esophagus	ESCC	5.18e-16	7.63e-01	0.0875

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:000915014	Breast	IDC	purine ribonucleotide metabolic process	55/1434	368/18723	1.30e-06	5.72e-05	55
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:000925914	Breast	IDC	ribonucleotide metabolic process	56/1434	385/18723	2.47e-06	9.63e-05	56
GO:000616314	Breast	IDC	purine nucleotide metabolic process	56/1434	396/18723	5.90e-06	1.90e-04	56
GO:007252114	Breast	IDC	purine-containing compound metabolic process	57/1434	416/18723	1.28e-05	3.31e-04	57
GO:190136112	Breast	IDC	organic cyclic compound catabolic process	56/1434	495/18723	2.12e-03	1.99e-02	56
GO:004670012	Breast	IDC	heterocycle catabolic process	51/1434	445/18723	2.51e-03	2.25e-02	51
GO:003465513	Breast	IDC	nucleobase-containing compound catabolic process	47/1434	407/18723	3.12e-03	2.63e-02	47
GO:004427012	Breast	IDC	cellular nitrogen compound catabolic process	50/1434	451/18723	5.29e-03	3.93e-02	50
GO:001943912	Breast	IDC	aromatic compound catabolic process	51/1434	467/18723	6.54e-03	4.59e-02	51
GO:001969324	Breast	DCIS	ribose phosphate metabolic process	58/1390	396/18723	4.80e-07	2.11e-05	58
GO:000915024	Breast	DCIS	purine ribonucleotide metabolic process	55/1390	368/18723	4.92e-07	2.14e-05	55
GO:000925924	Breast	DCIS	ribonucleotide metabolic process	56/1390	385/18723	9.44e-07	3.79e-05	56
GO:000616324	Breast	DCIS	purine nucleotide metabolic process	56/1390	396/18723	2.31e-06	8.29e-05	56
GO:000911723	Breast	DCIS	nucleotide metabolic process	65/1390	489/18723	3.19e-06	1.03e-04	65
GO:007252124	Breast	DCIS	purine-containing compound metabolic process	57/1390	416/18723	5.07e-06	1.48e-04	57
GO:000675323	Breast	DCIS	nucleoside phosphate metabolic process	65/1390	497/18723	5.51e-06	1.59e-04	65
GO:003465522	Breast	DCIS	nucleobase-containing compound catabolic process	47/1390	407/18723	1.69e-03	1.68e-02	47

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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

NUDT8

SNV

Missense_Mutation

rs569654818

c.643C>T

p.Arg215Cys

p.R215C

Q8WV74

protein_coding

tolerated_low_confidence(0.11)

benign(0.012)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NUDT8

SNV

Missense_Mutation

novel

c.530N>T

p.Arg177Leu

p.R177L

Q8WV74

protein_coding

deleterious(0)

benign(0.357)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

NUDT8

SNV

Missense_Mutation

novel

c.580N>A

p.Ala194Thr

p.A194T

Q8WV74

protein_coding

tolerated(0.2)

benign(0.236)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NUDT8

SNV

Missense_Mutation

rs745587907

c.235G>C

p.Val79Leu

p.V79L

Q8WV74

protein_coding

tolerated(0.1)

benign(0.068)

TCGA-BG-A0VZ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

NUDT8

SNV

Missense_Mutation

rs201447359

c.479N>A

p.Arg160Gln

p.R160Q

Q8WV74

protein_coding

tolerated(1)

benign(0)

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NUDT8

SNV

Missense_Mutation

novel

c.701N>C

p.Lys234Thr

p.K234T

Q8WV74

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.746)

TCGA-EO-A3B0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

NUDT8

SNV

Missense_Mutation

novel

c.620G>A

p.Cys207Tyr

p.C207Y

Q8WV74

protein_coding

tolerated_low_confidence(1)

benign(0.014)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

NUDT8

SNV

Missense_Mutation

rs745587907

c.235N>C

p.Val79Leu

p.V79L

Q8WV74

protein_coding

tolerated(0.1)

benign(0.068)

TCGA-43-6770-01

Lung

lung squamous cell carcinoma

Female

<65

I/II

Vaccine

recprame+as15

NUDT8

SNV

Missense_Mutation

novel

c.77G>T

p.Arg26Leu

p.R26L

Q8WV74

protein_coding

deleterious(0.02)

benign(0.326)

TCGA-85-8352-01

Lung

lung squamous cell carcinoma

Male

>=65

III/IV

Unknown

NUDT8

SNV

Missense_Mutation

novel

c.340N>T

p.Val114Leu

p.V114L

Q8WV74

protein_coding

deleterious(0.01)

possibly_damaging(0.611)

TCGA-85-A4JB-01

Lung

lung squamous cell carcinoma

Male

>=65

I/II

Chemotherapy

unknown

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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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