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:000268312	Cervix	HSIL_HPV	negative regulation of immune system process	39/737	434/18723	1.51e-06	6.60e-05	39
GO:004593615	Cervix	HSIL_HPV	negative regulation of phosphate metabolic process	36/737	441/18723	3.12e-05	8.94e-04	36
GO:001056315	Cervix	HSIL_HPV	negative regulation of phosphorus metabolic process	36/737	442/18723	3.27e-05	9.16e-04	36
GO:000193314	Cervix	HSIL_HPV	negative regulation of protein phosphorylation	30/737	342/18723	3.80e-05	1.03e-03	30
GO:004232614	Cervix	HSIL_HPV	negative regulation of phosphorylation	32/737	385/18723	6.03e-05	1.44e-03	32
GO:00713533	Cervix	HSIL_HPV	cellular response to interleukin-4	7/737	33/18723	2.48e-04	4.30e-03	7
GO:001922111	Cervix	HSIL_HPV	cytokine-mediated signaling pathway	35/737	472/18723	2.64e-04	4.52e-03	35
GO:00706703	Cervix	HSIL_HPV	response to interleukin-4	7/737	36/18723	4.38e-04	6.51e-03	7
GO:00507771	Cervix	HSIL_HPV	negative regulation of immune response	17/737	194/18723	1.76e-03	1.88e-02	17
GO:003210211	Cervix	HSIL_HPV	negative regulation of response to external stimulus	29/737	420/18723	2.53e-03	2.48e-02	29
GO:000283111	Cervix	HSIL_HPV	regulation of response to biotic stimulus	24/737	327/18723	2.65e-03	2.55e-02	24
GO:0060759	Cervix	HSIL_HPV	regulation of response to cytokine stimulus	14/737	162/18723	4.88e-03	4.02e-02	14
GO:0001959	Cervix	HSIL_HPV	regulation of cytokine-mediated signaling pathway	13/737	150/18723	6.39e-03	4.96e-02	13
GO:00105632	Colorectum	MSS	negative regulation of phosphorus metabolic process	118/3467	442/18723	1.18e-05	2.77e-04	118
GO:00459362	Colorectum	MSS	negative regulation of phosphate metabolic process	117/3467	441/18723	1.74e-05	3.84e-04	117
GO:00423262	Colorectum	MSS	negative regulation of phosphorylation	103/3467	385/18723	3.76e-05	7.17e-04	103
GO:00019332	Colorectum	MSS	negative regulation of protein phosphorylation	93/3467	342/18723	4.54e-05	8.35e-04	93
GO:0060333	Colorectum	MSS	interferon-gamma-mediated signaling pathway	11/3467	27/18723	6.03e-03	4.04e-02	11
GO:00459363	Colorectum	MSI-H	negative regulation of phosphate metabolic process	53/1319	441/18723	9.54e-05	3.01e-03	53
GO:00105633	Colorectum	MSI-H	negative regulation of phosphorus metabolic process	53/1319	442/18723	1.01e-04	3.16e-03	53

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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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