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: PARP16

Gene summary for PARP16

Gene summary.

Gene information	Species	Human
	Gene symbol	PARP16
	Gene ID	54956
	Gene name	poly(ADP-ribose) polymerase family member 16
	Gene Alias	ARTD15
	Cytomap	15q22.31
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q8N5Y8

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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
54956	PARP16	HCC1_Meng	Human	Liver	HCC	7.46e-07	1.20e-02	0.0246
54956	PARP16	HCC2	Human	Liver	HCC	1.49e-08	2.05e+00	0.5341
54956	PARP16	S014	Human	Liver	HCC	3.89e-04	1.18e-01	0.2254
54956	PARP16	S027	Human	Liver	HCC	1.23e-13	1.69e+00	0.2446
54956	PARP16	S028	Human	Liver	HCC	6.50e-21	3.08e+00	0.2503
54956	PARP16	S029	Human	Liver	HCC	1.43e-12	2.05e+00	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:001603222	Liver	HCC	viral process	286/7958	415/18723	4.41e-28	1.86e-25	286
GO:003497612	Liver	HCC	response to endoplasmic reticulum stress	189/7958	256/18723	1.43e-24	4.06e-22	189
GO:003596612	Liver	HCC	response to topologically incorrect protein	123/7958	159/18723	2.60e-19	3.44e-17	123
GO:000911722	Liver	HCC	nucleotide metabolic process	300/7958	489/18723	1.61e-17	1.71e-15	300
GO:000675322	Liver	HCC	nucleoside phosphate metabolic process	304/7958	497/18723	1.78e-17	1.85e-15	304
GO:001908021	Liver	HCC	viral gene expression	77/7958	94/18723	4.33e-15	3.12e-13	77
GO:000698612	Liver	HCC	response to unfolded protein	103/7958	137/18723	6.50e-15	4.48e-13	103
GO:003596712	Liver	HCC	cellular response to topologically incorrect protein	89/7958	116/18723	5.61e-14	3.39e-12	89
GO:003462012	Liver	HCC	cellular response to unfolded protein	71/7958	96/18723	3.70e-10	1.22e-08	71
GO:003096811	Liver	HCC	endoplasmic reticulum unfolded protein response	56/7958	74/18723	6.47e-09	1.67e-07	56
GO:000916512	Liver	HCC	nucleotide biosynthetic process	150/7958	254/18723	6.79e-08	1.40e-06	150
GO:190129312	Liver	HCC	nucleoside phosphate biosynthetic process	151/7958	256/18723	6.84e-08	1.41e-06	151
GO:001908211	Liver	HCC	viral protein processing	23/7958	29/18723	5.86e-05	5.38e-04	23
GO:007190021	Liver	HCC	regulation of protein serine/threonine kinase activity	189/7958	359/18723	5.97e-05	5.47e-04	189
GO:004586021	Liver	HCC	positive regulation of protein kinase activity	194/7958	386/18723	1.16e-03	6.54e-03	194
GO:003367411	Liver	HCC	positive regulation of kinase activity	230/7958	467/18723	1.72e-03	8.95e-03	230
GO:0072525	Liver	HCC	pyridine-containing compound biosynthetic process	22/7958	32/18723	2.43e-03	1.18e-02	22
GO:0072524	Liver	HCC	pyridine-containing compound metabolic process	25/7958	38/18723	3.18e-03	1.47e-02	25
GO:0070213	Liver	HCC	protein auto-ADP-ribosylation	10/7958	12/18723	4.79e-03	2.02e-02	10
GO:003649811	Liver	HCC	IRE1-mediated unfolded protein response	14/7958	19/18723	5.94e-03	2.44e-02	14

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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

PARP16

SNV

Missense_Mutation

c.418G>A

p.Glu140Lys

p.E140K

Q8N5Y8

protein_coding

tolerated(0.21)

benign(0.043)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP16

SNV

Missense_Mutation

rs762932743

c.776N>G

p.Asn259Ser

p.N259S

Q8N5Y8

protein_coding

tolerated(0.05)

possibly_damaging(0.768)

TCGA-E2-A1LA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

PARP16

insertion

In_Frame_Ins

novel

c.198_199insGTTTGTGAGAGACTCATTTCTTTTCCAAGTAATGACTCAGATTAC

p.Pro66_Asn67insValCysGluArgLeuIleSerPheProSerAsnAspSerAspTyr

p.P66_N67insVCERLISFPSNDSDY

Q8N5Y8

protein_coding

TCGA-A8-A09K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

PARP16

SNV

Missense_Mutation

c.434G>T

p.Arg145Leu

p.R145L

Q8N5Y8

protein_coding

tolerated(0.07)

benign(0.34)

TCGA-Q1-A73R-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

PARP16

SNV

Missense_Mutation

c.413N>G

p.Phe138Cys

p.F138C

Q8N5Y8

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-CA-6718-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

PARP16

SNV

Missense_Mutation

novel

c.782N>C

p.Gln261Pro

p.Q261P

Q8N5Y8

protein_coding

deleterious(0.01)

possibly_damaging(0.464)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

PARP16

SNV

Missense_Mutation

novel

c.353N>A

p.Pro118His

p.P118H

Q8N5Y8

protein_coding

deleterious(0.01)

possibly_damaging(0.632)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

PARP16

SNV

Missense_Mutation

rs374649627

c.463N>T

p.Arg155Cys

p.R155C

Q8N5Y8

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PARP16

SNV

Missense_Mutation

novel

c.256N>A

p.Val86Met

p.V86M

Q8N5Y8

protein_coding

tolerated(0.14)

benign(0.003)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

PARP16

SNV

Missense_Mutation

novel

c.706N>T

p.Asp236Tyr

p.D236Y

Q8N5Y8

protein_coding

deleterious(0.01)

probably_damaging(0.951)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

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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