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: IVNS1ABP

Gene summary for IVNS1ABP

Gene summary.

Gene information	Species	Human
	Gene symbol	IVNS1ABP
	Gene ID	10625
	Gene name	influenza virus NS1A binding protein
	Gene Alias	ARA3
	Cytomap	1q25.3
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q9Y6Y0

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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
10625	IVNS1ABP	LZE4T	Human	Esophagus	ESCC	2.73e-07	5.15e-01	0.0811
10625	IVNS1ABP	LZE5T	Human	Esophagus	ESCC	4.37e-02	-1.96e-01	0.0514
10625	IVNS1ABP	LZE7T	Human	Esophagus	ESCC	7.73e-13	1.76e+00	0.0667
10625	IVNS1ABP	LZE8T	Human	Esophagus	ESCC	3.95e-06	1.18e-01	0.067
10625	IVNS1ABP	LZE24T	Human	Esophagus	ESCC	3.45e-07	6.14e-01	0.0596
10625	IVNS1ABP	P1T-E	Human	Esophagus	ESCC	3.86e-07	7.02e-01	0.0875
10625	IVNS1ABP	P2T-E	Human	Esophagus	ESCC	4.82e-14	3.87e-01	0.1177
10625	IVNS1ABP	P4T-E	Human	Esophagus	ESCC	7.71e-07	3.51e-01	0.1323
10625	IVNS1ABP	P5T-E	Human	Esophagus	ESCC	1.30e-05	2.92e-01	0.1327
10625	IVNS1ABP	P8T-E	Human	Esophagus	ESCC	3.99e-09	2.47e-01	0.0889
10625	IVNS1ABP	P9T-E	Human	Esophagus	ESCC	6.83e-14	6.51e-01	0.1131
10625	IVNS1ABP	P10T-E	Human	Esophagus	ESCC	3.67e-19	5.01e-01	0.116
10625	IVNS1ABP	P11T-E	Human	Esophagus	ESCC	2.02e-13	2.22e+00	0.1426
10625	IVNS1ABP	P12T-E	Human	Esophagus	ESCC	1.92e-21	8.00e-01	0.1122
10625	IVNS1ABP	P15T-E	Human	Esophagus	ESCC	3.69e-32	1.08e+00	0.1149
10625	IVNS1ABP	P16T-E	Human	Esophagus	ESCC	2.61e-22	7.56e-01	0.1153
10625	IVNS1ABP	P20T-E	Human	Esophagus	ESCC	1.49e-14	6.74e-01	0.1124
10625	IVNS1ABP	P21T-E	Human	Esophagus	ESCC	6.73e-21	7.39e-01	0.1617
10625	IVNS1ABP	P22T-E	Human	Esophagus	ESCC	5.59e-10	6.44e-02	0.1236
10625	IVNS1ABP	P23T-E	Human	Esophagus	ESCC	2.92e-20	6.34e-01	0.108

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:0008380111	Esophagus	ESCC	RNA splicing	336/8552	434/18723	1.74e-42	3.67e-39	336
GO:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:1903320111	Esophagus	ESCC	regulation of protein modification by small protein conjugation or removal	181/8552	242/18723	1.80e-20	2.60e-18	181
GO:2001242111	Esophagus	ESCC	regulation of intrinsic apoptotic signaling pathway	128/8552	164/18723	1.75e-17	1.50e-15	128
GO:0031396111	Esophagus	ESCC	regulation of protein ubiquitination	154/8552	210/18723	2.70e-16	2.04e-14	154
GO:2001234111	Esophagus	ESCC	negative regulation of apoptotic signaling pathway	161/8552	224/18723	1.24e-15	8.09e-14	161
GO:000961518	Esophagus	ESCC	response to virus	238/8552	367/18723	6.65e-14	3.32e-12	238
GO:2001243111	Esophagus	ESCC	negative regulation of intrinsic apoptotic signaling pathway	78/8552	98/18723	5.50e-12	2.10e-10	78
GO:00063833	Esophagus	ESCC	transcription by RNA polymerase III	41/8552	46/18723	7.69e-10	1.90e-08	41
GO:0031397111	Esophagus	ESCC	negative regulation of protein ubiquitination	63/8552	83/18723	1.87e-08	3.65e-07	63
GO:1903321111	Esophagus	ESCC	negative regulation of protein modification by small protein conjugation or removal	69/8552	95/18723	8.54e-08	1.44e-06	69
GO:000838012	Liver	Cirrhotic	RNA splicing	229/4634	434/18723	9.13e-37	2.86e-33	229
GO:200123312	Liver	Cirrhotic	regulation of apoptotic signaling pathway	163/4634	356/18723	2.62e-18	4.43e-16	163
GO:009719312	Liver	Cirrhotic	intrinsic apoptotic signaling pathway	130/4634	288/18723	2.69e-14	2.45e-12	130
GO:20012427	Liver	Cirrhotic	regulation of intrinsic apoptotic signaling pathway	82/4634	164/18723	2.35e-12	1.71e-10	82
GO:20012347	Liver	Cirrhotic	negative regulation of apoptotic signaling pathway	102/4634	224/18723	8.40e-12	5.60e-10	102
GO:190332012	Liver	Cirrhotic	regulation of protein modification by small protein conjugation or removal	105/4634	242/18723	1.43e-10	7.43e-09	105
GO:003139612	Liver	Cirrhotic	regulation of protein ubiquitination	89/4634	210/18723	1.40e-08	5.30e-07	89
GO:20012437	Liver	Cirrhotic	negative regulation of intrinsic apoptotic signaling pathway	47/4634	98/18723	5.26e-07	1.17e-05	47

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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

IVNS1ABP

SNV

Missense_Mutation

novel

c.1711C>G

p.His571Asp

p.H571D

Q9Y6Y0

protein_coding

tolerated(0.07)

possibly_damaging(0.872)

TCGA-AC-A3W6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

IVNS1ABP

SNV

Missense_Mutation

c.203N>G

p.His68Arg

p.H68R

Q9Y6Y0

protein_coding

tolerated(0.43)

benign(0.265)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IVNS1ABP

SNV

Missense_Mutation

c.888G>C

p.Lys296Asn

p.K296N

Q9Y6Y0

protein_coding

tolerated(0.09)

probably_damaging(0.915)

TCGA-AR-A24H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

IVNS1ABP

SNV

Missense_Mutation

c.523N>T

p.Arg175Trp

p.R175W

Q9Y6Y0

protein_coding

tolerated(0.19)

probably_damaging(1)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

IVNS1ABP

insertion

In_Frame_Ins

novel

c.931_932insCTTTTTCTCATTGTGCAGATT

p.Ile311delinsThrPheSerHisCysAlaAspLeu

p.I311delinsTFSHCADL

Q9Y6Y0

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

IVNS1ABP

insertion

Nonsense_Mutation

novel

c.929_930insCATCCTTAAAAAGTTTTAA

p.Phe312LeufsTer5

p.F312Lfs*5

Q9Y6Y0

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

IVNS1ABP

SNV

Missense_Mutation

novel

c.142G>T

p.Ala48Ser

p.A48S

Q9Y6Y0

protein_coding

deleterious(0.03)

probably_damaging(0.998)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IVNS1ABP

SNV

Missense_Mutation

novel

c.1309G>A

p.Asp437Asn

p.D437N

Q9Y6Y0

protein_coding

tolerated(0.32)

benign(0.013)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IVNS1ABP

SNV

Missense_Mutation

novel

c.1696N>A

p.Gly566Ser

p.G566S

Q9Y6Y0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-VS-A9UI-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

IVNS1ABP

SNV

Missense_Mutation

novel

c.1912N>C

p.Lys638Gln

p.K638Q

Q9Y6Y0

protein_coding

tolerated_low_confidence(0.18)

benign(0.001)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

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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