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: IWS1

Gene summary for IWS1

Gene summary.

Gene information	Species	Human
	Gene symbol	IWS1
	Gene ID	55677
	Gene name	interacts with SUPT6H, CTD assembly factor 1
	Gene Alias	IWS1
	Cytomap	2q14.3
	Gene Type	protein-coding
	GO ID	GO:0000414
	UniProtAcc	Q96ST2

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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
55677	IWS1	CCI_1	Human	Cervix	CC	5.24e-03	5.04e-01	0.528
55677	IWS1	CCI_2	Human	Cervix	CC	3.61e-02	4.80e-01	0.5249
55677	IWS1	CCI_3	Human	Cervix	CC	3.09e-03	5.18e-01	0.516
55677	IWS1	LZE4T	Human	Esophagus	ESCC	2.53e-12	3.51e-01	0.0811
55677	IWS1	LZE5T	Human	Esophagus	ESCC	3.01e-08	3.75e-01	0.0514
55677	IWS1	LZE7T	Human	Esophagus	ESCC	2.01e-11	4.77e-01	0.0667
55677	IWS1	LZE8T	Human	Esophagus	ESCC	1.54e-09	1.71e-01	0.067
55677	IWS1	LZE20T	Human	Esophagus	ESCC	4.34e-12	1.56e-01	0.0662
55677	IWS1	LZE22T	Human	Esophagus	ESCC	8.37e-09	4.00e-01	0.068
55677	IWS1	LZE24T	Human	Esophagus	ESCC	3.80e-12	3.29e-01	0.0596
55677	IWS1	P1T-E	Human	Esophagus	ESCC	1.68e-14	4.70e-01	0.0875
55677	IWS1	P2T-E	Human	Esophagus	ESCC	7.11e-29	4.64e-01	0.1177
55677	IWS1	P4T-E	Human	Esophagus	ESCC	9.26e-29	6.79e-01	0.1323
55677	IWS1	P5T-E	Human	Esophagus	ESCC	1.07e-28	5.30e-01	0.1327
55677	IWS1	P8T-E	Human	Esophagus	ESCC	6.78e-19	3.23e-01	0.0889
55677	IWS1	P9T-E	Human	Esophagus	ESCC	9.99e-23	3.80e-01	0.1131
55677	IWS1	P10T-E	Human	Esophagus	ESCC	1.16e-29	6.15e-01	0.116
55677	IWS1	P11T-E	Human	Esophagus	ESCC	3.73e-13	4.58e-01	0.1426
55677	IWS1	P12T-E	Human	Esophagus	ESCC	4.43e-35	6.94e-01	0.1122
55677	IWS1	P15T-E	Human	Esophagus	ESCC	1.97e-26	6.07e-01	0.1149

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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
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:190331111	Liver	Cirrhotic	regulation of mRNA metabolic process	140/4634	288/18723	1.07e-18	1.91e-16	140
GO:005068411	Liver	Cirrhotic	regulation of mRNA processing	81/4634	137/18723	1.05e-17	1.60e-15	81
GO:003238611	Liver	Cirrhotic	regulation of intracellular transport	147/4634	337/18723	1.84e-14	1.72e-12	147
GO:000640312	Liver	Cirrhotic	RNA localization	94/4634	201/18723	8.57e-12	5.66e-10	94
GO:000691312	Liver	Cirrhotic	nucleocytoplasmic transport	118/4634	301/18723	1.71e-08	6.27e-07	118
GO:005116912	Liver	Cirrhotic	nuclear transport	118/4634	301/18723	1.71e-08	6.27e-07	118
GO:00064731	Liver	Cirrhotic	protein acetylation	84/4634	201/18723	7.50e-08	2.25e-06	84
GO:00183941	Liver	Cirrhotic	peptidyl-lysine acetylation	73/4634	169/18723	1.08e-07	3.07e-06	73
GO:004682211	Liver	Cirrhotic	regulation of nucleocytoplasmic transport	51/4634	106/18723	1.54e-07	4.12e-06	51
GO:005123611	Liver	Cirrhotic	establishment of RNA localization	71/4634	166/18723	2.56e-07	6.41e-06	71
GO:005116812	Liver	Cirrhotic	nuclear export	67/4634	154/18723	2.57e-07	6.41e-06	67
GO:00435431	Liver	Cirrhotic	protein acylation	95/4634	243/18723	4.73e-07	1.07e-05	95
GO:00506576	Liver	Cirrhotic	nucleic acid transport	69/4634	163/18723	5.97e-07	1.30e-05	69
GO:00506586	Liver	Cirrhotic	RNA transport	69/4634	163/18723	5.97e-07	1.30e-05	69
GO:00159316	Liver	Cirrhotic	nucleobase-containing compound transport	87/4634	222/18723	1.25e-06	2.52e-05	87
GO:00182051	Liver	Cirrhotic	peptidyl-lysine modification	134/4634	376/18723	1.29e-06	2.59e-05	134
GO:00510282	Liver	Cirrhotic	mRNA transport	56/4634	130/18723	3.47e-06	5.97e-05	56
GO:00064751	Liver	Cirrhotic	internal protein amino acid acetylation	65/4634	160/18723	6.66e-06	1.04e-04	65
GO:00183931	Liver	Cirrhotic	internal peptidyl-lysine acetylation	64/4634	158/18723	8.75e-06	1.29e-04	64
GO:001657011	Liver	Cirrhotic	histone modification	154/4634	463/18723	1.92e-05	2.57e-04	154

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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

IWS1

SNV

Missense_Mutation

c.1447G>A

p.Glu483Lys

p.E483K

Q96ST2

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-E2-A14P-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Targeted Molecular therapy

trastuzumab

IWS1

insertion

In_Frame_Ins

novel

c.1954_1955insATATACTTTCTTTCATGGTCATTGTAGCAGCTA

p.Leu652delinsHisIleLeuSerPheMetValIleValAlaAlaMet

p.L652delinsHILSFMVIVAAM

Q96ST2

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

IWS1

SNV

Missense_Mutation

c.1900C>T

p.Arg634Trp

p.R634W

Q96ST2

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IWS1

SNV

Missense_Mutation

c.1189N>T

p.Leu397Phe

p.L397F

Q96ST2

protein_coding

deleterious(0.04)

probably_damaging(0.998)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

IWS1

SNV

Missense_Mutation

novel

c.2072G>A

p.Gly691Asp

p.G691D

Q96ST2

protein_coding

deleterious(0.02)

probably_damaging(0.972)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

IWS1

SNV

Missense_Mutation

rs768095036

c.247N>A

p.Glu83Lys

p.E83K

Q96ST2

protein_coding

tolerated_low_confidence(0.11)

possibly_damaging(0.664)

TCGA-EA-A3QD-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

IWS1

SNV

Missense_Mutation

c.2389G>A

p.Asp797Asn

p.D797N

Q96ST2

protein_coding

deleterious(0.03)

benign(0.101)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

IWS1

SNV

Missense_Mutation

c.476N>A

p.Ser159Tyr

p.S159Y

Q96ST2

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.98)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IWS1

insertion

Frame_Shift_Ins

novel

c.2069_2070insCCTAA

p.Gly691LeufsTer11

p.G691Lfs*11

Q96ST2

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

IWS1

SNV

Missense_Mutation

c.1691N>A

p.Ile564Asn

p.I564N

Q96ST2

protein_coding

deleterious(0)

probably_damaging(0.929)

TCGA-CK-4951-01

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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