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: PARP14

Gene summary for PARP14

Gene summary.

Gene information	Species	Human
	Gene symbol	PARP14
	Gene ID	54625
	Gene name	poly(ADP-ribose) polymerase family member 14
	Gene Alias	ARTD8
	Cytomap	3q21.1
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q460N5

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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
54625	PARP14	CA_HPV_1	Human	Cervix	CC	5.08e-14	5.03e-01	0.0264
54625	PARP14	CA_HPV_2	Human	Cervix	CC	1.09e-12	5.47e-01	0.0391
54625	PARP14	HSIL_HPV_2	Human	Cervix	HSIL_HPV	3.96e-06	3.16e-01	0.0208
54625	PARP14	CCI_2	Human	Cervix	CC	2.36e-16	2.01e+00	0.5249
54625	PARP14	CCI_3	Human	Cervix	CC	3.29e-17	1.48e+00	0.516
54625	PARP14	Tumor	Human	Cervix	CC	1.87e-06	3.53e-01	0.1241
54625	PARP14	sample1	Human	Cervix	CC	8.03e-17	8.78e-01	0.0959
54625	PARP14	sample3	Human	Cervix	CC	3.01e-24	5.44e-01	0.1387
54625	PARP14	T1	Human	Cervix	CC	9.14e-47	1.04e+00	0.0918
54625	PARP14	T3	Human	Cervix	CC	1.54e-19	4.69e-01	0.1389
54625	PARP14	HTA11_99999970781_79442	Human	Colorectum	MSS	1.52e-12	8.34e-01	0.294
54625	PARP14	HTA11_99999965062_69753	Human	Colorectum	MSI-H	9.93e-03	1.10e+00	0.3487
54625	PARP14	A015-C-203	Human	Colorectum	FAP	1.61e-06	2.84e-01	-0.1294
54625	PARP14	A001-C-108	Human	Colorectum	FAP	1.49e-03	4.31e-01	-0.0272
54625	PARP14	A002-C-205	Human	Colorectum	FAP	4.69e-06	3.10e-01	-0.1236
54625	PARP14	A015-C-006	Human	Colorectum	FAP	3.90e-05	3.69e-01	-0.0994
54625	PARP14	A015-C-104	Human	Colorectum	FAP	3.81e-06	2.72e-01	-0.1899
54625	PARP14	A002-C-116	Human	Colorectum	FAP	1.26e-04	1.77e-01	-0.0452
54625	PARP14	A018-E-020	Human	Colorectum	FAP	1.26e-02	1.95e-01	-0.2034
54625	PARP14	LZE4T	Human	Esophagus	ESCC	2.39e-11	3.35e-01	0.0811

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00026837	Cervix	CC	negative regulation of immune system process	94/2311	434/18723	2.63e-08	1.87e-06	94
GO:004593610	Cervix	CC	negative regulation of phosphate metabolic process	88/2311	441/18723	2.92e-06	8.27e-05	88
GO:001056310	Cervix	CC	negative regulation of phosphorus metabolic process	88/2311	442/18723	3.21e-06	8.77e-05	88
GO:004232610	Cervix	CC	negative regulation of phosphorylation	77/2311	385/18723	1.09e-05	2.38e-04	77
GO:00028315	Cervix	CC	regulation of response to biotic stimulus	67/2311	327/18723	1.79e-05	3.36e-04	67
GO:000193310	Cervix	CC	negative regulation of protein phosphorylation	69/2311	342/18723	2.29e-05	4.01e-04	69
GO:00028322	Cervix	CC	negative regulation of response to biotic stimulus	27/2311	108/18723	2.27e-04	2.55e-03	27
GO:00192213	Cervix	CC	cytokine-mediated signaling pathway	84/2311	472/18723	3.25e-04	3.44e-03	84
GO:00507773	Cervix	CC	negative regulation of immune response	41/2311	194/18723	3.63e-04	3.76e-03	41
GO:00321022	Cervix	CC	negative regulation of response to external stimulus	75/2311	420/18723	5.96e-04	5.61e-03	75
GO:00450882	Cervix	CC	regulation of innate immune response	44/2311	218/18723	6.40e-04	5.97e-03	44
GO:00343415	Cervix	CC	response to interferon-gamma	30/2311	141/18723	1.88e-03	1.39e-02	30
GO:00458243	Cervix	CC	negative regulation of innate immune response	18/2311	71/18723	2.01e-03	1.47e-02	18
GO:0031348	Cervix	CC	negative regulation of defense response	48/2311	258/18723	2.30e-03	1.65e-02	48
GO:00603333	Cervix	CC	interferon-gamma-mediated signaling pathway	9/2311	27/18723	3.82e-03	2.41e-02	9
GO:00713463	Cervix	CC	cellular response to interferon-gamma	25/2311	118/18723	4.54e-03	2.75e-02	25
GO:00019612	Cervix	CC	positive regulation of cytokine-mediated signaling pathway	13/2311	50/18723	6.42e-03	3.58e-02	13
GO:00607602	Cervix	CC	positive regulation of response to cytokine stimulus	14/2311	57/18723	8.17e-03	4.25e-02	14
GO:00603303	Cervix	CC	regulation of response to interferon-gamma	6/2311	16/18723	9.35e-03	4.66e-02	6
GO:00603343	Cervix	CC	regulation of interferon-gamma-mediated signaling pathway	6/2311	16/18723	9.35e-03	4.66e-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

PARP14

SNV

Missense_Mutation

c.2578C>G

p.Leu860Val

p.L860V

Q460N5

protein_coding

tolerated(0.53)

benign(0.047)

TCGA-A2-A1FV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

PARP14

SNV

Missense_Mutation

novel

c.2665N>A

p.Glu889Lys

p.E889K

Q460N5

protein_coding

tolerated(0.14)

benign(0.037)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP14

SNV

Missense_Mutation

c.2473N>A

p.Glu825Lys

p.E825K

Q460N5

protein_coding

deleterious(0.02)

possibly_damaging(0.749)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP14

SNV

Missense_Mutation

c.4653N>T

p.Met1551Ile

p.M1551I

Q460N5

protein_coding

tolerated(1)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP14

SNV

Missense_Mutation

c.142N>T

p.Pro48Ser

p.P48S

Q460N5

protein_coding

tolerated(0.07)

possibly_damaging(0.609)

TCGA-B6-A0RH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

PARP14

SNV

Missense_Mutation

novel

c.5212N>A

p.Val1738Met

p.V1738M

Q460N5

protein_coding

tolerated(1)

benign(0)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

PARP14

SNV

Missense_Mutation

novel

c.2375G>C

p.Cys792Ser

p.C792S

Q460N5

protein_coding

tolerated(0.19)

benign(0.003)

TCGA-BH-A0HU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

PARP14

SNV

Missense_Mutation

c.763N>C

p.Gly255Arg

p.G255R

Q460N5

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-C8-A134-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

PARP14

SNV

Missense_Mutation

c.4396G>C

p.Asp1466His

p.D1466H

Q460N5

protein_coding

tolerated(0.13)

benign(0.048)

TCGA-E2-A1LH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

PARP14

SNV

Missense_Mutation

c.3835N>G

p.Gln1279Glu

p.Q1279E

Q460N5

protein_coding

tolerated(1)

benign(0.372)

TCGA-GM-A2DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

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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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