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: PARP9

Gene summary for PARP9

Gene summary.

Gene information	Species	Human
	Gene symbol	PARP9
	Gene ID	83666
	Gene name	poly(ADP-ribose) polymerase family member 9
	Gene Alias	ARTD9
	Cytomap	3q21.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q8IXQ6

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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
83666	PARP9	CA_HPV_1	Human	Cervix	CC	6.64e-06	2.89e-01	0.0264
83666	PARP9	CA_HPV_2	Human	Cervix	CC	1.87e-05	2.90e-01	0.0391
83666	PARP9	CCI_1	Human	Cervix	CC	1.68e-04	7.68e-01	0.528
83666	PARP9	CCI_2	Human	Cervix	CC	1.70e-08	1.04e+00	0.5249
83666	PARP9	CCI_3	Human	Cervix	CC	6.34e-16	1.41e+00	0.516
83666	PARP9	Tumor	Human	Cervix	CC	5.47e-31	6.60e-01	0.1241
83666	PARP9	sample3	Human	Cervix	CC	6.88e-36	6.68e-01	0.1387
83666	PARP9	T3	Human	Cervix	CC	9.19e-33	6.38e-01	0.1389
83666	PARP9	HTA11_1391_2000001011	Human	Colorectum	AD	1.71e-04	4.04e-01	-0.059
83666	PARP9	HTA11_99999970781_79442	Human	Colorectum	MSS	1.92e-21	8.15e-01	0.294
83666	PARP9	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.32e-04	1.06e+00	0.3487
83666	PARP9	LZE4T	Human	Esophagus	ESCC	1.65e-13	4.30e-01	0.0811
83666	PARP9	LZE5T	Human	Esophagus	ESCC	1.39e-03	2.56e-01	0.0514
83666	PARP9	LZE7T	Human	Esophagus	ESCC	4.74e-02	2.99e-01	0.0667
83666	PARP9	LZE8T	Human	Esophagus	ESCC	1.17e-06	3.53e-01	0.067
83666	PARP9	LZE20T	Human	Esophagus	ESCC	1.01e-05	2.70e-01	0.0662
83666	PARP9	LZE22T	Human	Esophagus	ESCC	1.85e-02	1.70e-01	0.068
83666	PARP9	LZE24T	Human	Esophagus	ESCC	3.65e-38	1.11e+00	0.0596
83666	PARP9	LZE21T	Human	Esophagus	ESCC	1.03e-02	2.47e-01	0.0655
83666	PARP9	P1T-E	Human	Esophagus	ESCC	8.35e-14	7.49e-01	0.0875

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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:00603344	Oral cavity	EOLP	regulation of interferon-gamma-mediated signaling pathway	7/2218	16/18723	1.40e-03	9.58e-03	7
GO:00507301	Oral cavity	EOLP	regulation of peptidyl-tyrosine phosphorylation	48/2218	264/18723	1.61e-03	1.08e-02	48
GO:00181081	Oral cavity	EOLP	peptidyl-tyrosine phosphorylation	64/2218	375/18723	1.65e-03	1.09e-02	64
GO:200102213	Oral cavity	EOLP	positive regulation of response to DNA damage stimulus	23/2218	105/18723	2.44e-03	1.49e-02	23
GO:00063022	Oral cavity	EOLP	double-strand break repair	44/2218	251/18723	4.94e-03	2.62e-02	44
GO:20007811	Oral cavity	EOLP	positive regulation of double-strand break repair	11/2218	40/18723	5.53e-03	2.86e-02	11
GO:20007791	Oral cavity	EOLP	regulation of double-strand break repair	18/2218	85/18723	9.81e-03	4.43e-02	18
GO:001603233	Oral cavity	NEOLP	viral process	101/2005	415/18723	1.08e-15	5.85e-13	101
GO:003450432	Oral cavity	NEOLP	protein localization to nucleus	71/2005	290/18723	1.49e-11	2.21e-09	71
GO:000961531	Oral cavity	NEOLP	response to virus	80/2005	367/18723	3.70e-10	3.14e-08	80
GO:005109833	Oral cavity	NEOLP	regulation of binding	77/2005	363/18723	2.91e-09	1.76e-07	77
GO:005109933	Oral cavity	NEOLP	positive regulation of binding	46/2005	173/18723	3.51e-09	2.04e-07	46
GO:00019593	Oral cavity	NEOLP	regulation of cytokine-mediated signaling pathway	41/2005	150/18723	1.03e-08	5.12e-07	41
GO:00607593	Oral cavity	NEOLP	regulation of response to cytokine stimulus	43/2005	162/18723	1.19e-08	5.70e-07	43
GO:190382932	Oral cavity	NEOLP	positive regulation of cellular protein localization	61/2005	276/18723	2.63e-08	1.14e-06	61
GO:190018031	Oral cavity	NEOLP	regulation of protein localization to nucleus	37/2005	136/18723	6.09e-08	2.39e-06	37
GO:001922122	Oral cavity	NEOLP	cytokine-mediated signaling pathway	88/2005	472/18723	1.37e-07	4.80e-06	88
GO:005160731	Oral cavity	NEOLP	defense response to virus	57/2005	265/18723	1.97e-07	6.55e-06	57
GO:014054631	Oral cavity	NEOLP	defense response to symbiont	57/2005	265/18723	1.97e-07	6.55e-06	57
GO:003210323	Oral cavity	NEOLP	positive regulation of response to external stimulus	81/2005	427/18723	2.04e-07	6.74e-06	81

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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

PARP9

SNV

Missense_Mutation

novel

c.914N>A

p.Thr305Asn

p.T305N

Q8IXQ6

protein_coding

deleterious(0.04)

possibly_damaging(0.598)

TCGA-AC-A5EH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP9

SNV

Missense_Mutation

novel

c.1010N>A

p.Ser337Tyr

p.S337Y

Q8IXQ6

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP9

SNV

Missense_Mutation

c.2293G>A

p.Glu765Lys

p.E765K

Q8IXQ6

protein_coding

deleterious(0)

possibly_damaging(0.53)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PARP9

SNV

Missense_Mutation

c.152N>T

p.Ser51Leu

p.S51L

Q8IXQ6

protein_coding

deleterious(0.01)

benign(0.049)

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

PARP9

SNV

Missense_Mutation

novel

c.615N>A

p.Asp205Glu

p.D205E

Q8IXQ6

protein_coding

tolerated(0.53)

benign(0.022)

TCGA-BH-A8FY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP9

SNV

Missense_Mutation

c.170N>C

p.Gly57Ala

p.G57A

Q8IXQ6

protein_coding

tolerated(0.72)

benign(0.024)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP9

SNV

Missense_Mutation

c.1370A>C

p.His457Pro

p.H457P

Q8IXQ6

protein_coding

deleterious(0.01)

benign(0.015)

TCGA-E9-A1RF-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

PARP9

SNV

Missense_Mutation

novel

c.1903G>C

p.Asp635His

p.D635H

Q8IXQ6

protein_coding

tolerated(0.15)

possibly_damaging(0.751)

TCGA-EW-A3E8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrozole

PARP9

SNV

Missense_Mutation

c.1678N>T

p.Asp560Tyr

p.D560Y

Q8IXQ6

protein_coding

deleterious(0.03)

possibly_damaging(0.459)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

PARP9

insertion

Frame_Shift_Ins

novel

c.1041_1042insCAAAAAACAAACAAAACAACAA

p.Val348GlnfsTer19

p.V348Qfs*19

Q8IXQ6

protein_coding

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

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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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