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:00353372	Prostate	Tumor	fatty-acyl-CoA metabolic process	14/3246	38/18723	3.24e-03	1.69e-02	14
GO:0034655111	Skin	cSCC	nucleobase-containing compound catabolic process	172/4864	407/18723	4.11e-13	2.43e-11	172
GO:0046700110	Skin	cSCC	heterocycle catabolic process	178/4864	445/18723	4.45e-11	2.13e-09	178
GO:0044270110	Skin	cSCC	cellular nitrogen compound catabolic process	179/4864	451/18723	8.34e-11	3.79e-09	179
GO:0019439110	Skin	cSCC	aromatic compound catabolic process	183/4864	467/18723	1.76e-10	7.68e-09	183
GO:1901361110	Skin	cSCC	organic cyclic compound catabolic process	188/4864	495/18723	1.92e-09	7.01e-08	188
GO:0019693112	Skin	cSCC	ribose phosphate metabolic process	146/4864	396/18723	9.28e-07	1.68e-05	146
GO:000675324	Skin	cSCC	nucleoside phosphate metabolic process	176/4864	497/18723	1.55e-06	2.62e-05	176
GO:000911724	Skin	cSCC	nucleotide metabolic process	173/4864	489/18723	2.03e-06	3.35e-05	173
GO:0072521112	Skin	cSCC	purine-containing compound metabolic process	150/4864	416/18723	2.88e-06	4.54e-05	150
GO:0009259112	Skin	cSCC	ribonucleotide metabolic process	138/4864	385/18723	1.00e-05	1.30e-04	138
GO:0006163112	Skin	cSCC	purine nucleotide metabolic process	140/4864	396/18723	1.93e-05	2.27e-04	140
GO:0009150112	Skin	cSCC	purine ribonucleotide metabolic process	131/4864	368/18723	2.42e-05	2.76e-04	131
GO:00159362	Skin	cSCC	coenzyme A metabolic process	10/4864	18/18723	7.25e-03	3.44e-02	10
GO:00060844	Skin	cSCC	acetyl-CoA metabolic process	16/4864	35/18723	9.09e-03	4.16e-02	16
GO:00091506	Stomach	GC	purine ribonucleotide metabolic process	56/1159	368/18723	3.67e-10	5.39e-08	56
GO:00061636	Stomach	GC	purine nucleotide metabolic process	58/1159	396/18723	7.97e-10	1.11e-07	58
GO:00092595	Stomach	GC	ribonucleotide metabolic process	56/1159	385/18723	2.03e-09	2.69e-07	56
GO:00725216	Stomach	GC	purine-containing compound metabolic process	58/1159	416/18723	5.19e-09	5.76e-07	58
GO:00196935	Stomach	GC	ribose phosphate metabolic process	56/1159	396/18723	5.72e-09	6.22e-07	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

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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