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:003434131	Oral cavity	NEOLP	response to interferon-gamma	36/2005	141/18723	5.06e-07	1.52e-05	36
GO:000283131	Oral cavity	NEOLP	regulation of response to biotic stimulus	65/2005	327/18723	5.93e-07	1.74e-05	65
GO:190018231	Oral cavity	NEOLP	positive regulation of protein localization to nucleus	26/2005	87/18723	7.70e-07	2.14e-05	26
GO:005105231	Oral cavity	NEOLP	regulation of DNA metabolic process	63/2005	359/18723	5.48e-05	7.44e-04	63
GO:00450883	Oral cavity	NEOLP	regulation of innate immune response	43/2005	218/18723	5.49e-05	7.44e-04	43
GO:200102031	Oral cavity	NEOLP	regulation of response to DNA damage stimulus	43/2005	219/18723	6.13e-05	8.19e-04	43
GO:00607603	Oral cavity	NEOLP	positive regulation of response to cytokine stimulus	17/2005	57/18723	6.31e-05	8.33e-04	17
GO:005105431	Oral cavity	NEOLP	positive regulation of DNA metabolic process	40/2005	201/18723	8.01e-05	1.01e-03	40
GO:007134631	Oral cavity	NEOLP	cellular response to interferon-gamma	27/2005	118/18723	1.03e-04	1.24e-03	27
GO:00019613	Oral cavity	NEOLP	positive regulation of cytokine-mediated signaling pathway	15/2005	50/18723	1.56e-04	1.77e-03	15
GO:006033331	Oral cavity	NEOLP	interferon-gamma-mediated signaling pathway	10/2005	27/18723	2.94e-04	2.92e-03	10
GO:001908031	Oral cavity	NEOLP	viral gene expression	22/2005	94/18723	3.10e-04	3.05e-03	22
GO:00182122	Oral cavity	NEOLP	peptidyl-tyrosine modification	62/2005	378/18723	4.27e-04	3.91e-03	62
GO:00181082	Oral cavity	NEOLP	peptidyl-tyrosine phosphorylation	61/2005	375/18723	5.88e-04	5.08e-03	61
GO:003134922	Oral cavity	NEOLP	positive regulation of defense response	47/2005	278/18723	1.05e-03	7.99e-03	47
GO:00506882	Oral cavity	NEOLP	regulation of defense response to virus	16/2005	69/18723	2.17e-03	1.42e-02	16
GO:00506912	Oral cavity	NEOLP	regulation of defense response to virus by host	11/2005	41/18723	3.12e-03	1.89e-02	11
GO:200102221	Oral cavity	NEOLP	positive regulation of response to DNA damage stimulus	21/2005	105/18723	3.45e-03	2.05e-02	21
GO:006033011	Oral cavity	NEOLP	regulation of response to interferon-gamma	6/2005	16/18723	4.64e-03	2.56e-02	6
GO:006033411	Oral cavity	NEOLP	regulation of interferon-gamma-mediated signaling pathway	6/2005	16/18723	4.64e-03	2.56e-02	6

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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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