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: DHX9

Gene summary for DHX9

Gene summary.

Gene information	Species	Human
	Gene symbol	DHX9
	Gene ID	1660
	Gene name	DExH-box helicase 9
	Gene Alias	DDX9
	Cytomap	1q25.3
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	B3KU66

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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
1660	DHX9	HTA11_3410_2000001011	Human	Colorectum	AD	1.64e-02	-3.07e-01	0.0155
1660	DHX9	HTA11_866_2000001011	Human	Colorectum	AD	1.16e-02	-1.61e-01	-0.1001
1660	DHX9	HTA11_99999970781_79442	Human	Colorectum	MSS	3.66e-09	5.75e-01	0.294
1660	DHX9	A015-C-203	Human	Colorectum	FAP	1.15e-17	-2.52e-01	-0.1294
1660	DHX9	A002-C-201	Human	Colorectum	FAP	7.88e-06	-1.83e-01	0.0324
1660	DHX9	A002-C-203	Human	Colorectum	FAP	1.97e-02	-1.28e-01	0.2786
1660	DHX9	A001-C-119	Human	Colorectum	FAP	6.00e-04	-2.34e-01	-0.1557
1660	DHX9	A001-C-108	Human	Colorectum	FAP	1.31e-11	-2.87e-01	-0.0272
1660	DHX9	A002-C-205	Human	Colorectum	FAP	5.84e-13	-3.09e-01	-0.1236
1660	DHX9	A015-C-006	Human	Colorectum	FAP	3.13e-08	-2.44e-01	-0.0994
1660	DHX9	A015-C-106	Human	Colorectum	FAP	1.14e-09	-2.12e-01	-0.0511
1660	DHX9	A002-C-114	Human	Colorectum	FAP	5.45e-11	-3.06e-01	-0.1561
1660	DHX9	A015-C-104	Human	Colorectum	FAP	5.70e-20	-2.89e-01	-0.1899
1660	DHX9	A001-C-014	Human	Colorectum	FAP	7.68e-09	-2.11e-01	0.0135
1660	DHX9	A002-C-016	Human	Colorectum	FAP	1.61e-11	-2.49e-01	0.0521
1660	DHX9	A015-C-002	Human	Colorectum	FAP	1.70e-06	-2.55e-01	-0.0763
1660	DHX9	A001-C-203	Human	Colorectum	FAP	3.43e-05	-1.48e-01	-0.0481
1660	DHX9	A002-C-116	Human	Colorectum	FAP	2.34e-22	-3.38e-01	-0.0452
1660	DHX9	A014-C-008	Human	Colorectum	FAP	2.02e-07	-2.25e-01	-0.191
1660	DHX9	A018-E-020	Human	Colorectum	FAP	1.19e-10	-3.19e-01	-0.2034

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:005109022	Thyroid	ATC	regulation of DNA-binding transcription factor activity	190/6293	440/18723	1.49e-05	1.39e-04	190
GO:006014823	Thyroid	ATC	positive regulation of posttranscriptional gene silencing	22/6293	31/18723	2.35e-05	2.06e-04	22
GO:003248113	Thyroid	ATC	positive regulation of type I interferon production	35/6293	58/18723	2.70e-05	2.30e-04	35
GO:003461228	Thyroid	ATC	response to tumor necrosis factor	116/6293	253/18723	3.22e-05	2.68e-04	116
GO:000283123	Thyroid	ATC	regulation of response to biotic stimulus	144/6293	327/18723	4.94e-05	3.91e-04	144
GO:200063724	Thyroid	ATC	positive regulation of gene silencing by miRNA	21/6293	30/18723	5.03e-05	3.96e-04	21
GO:004683115	Thyroid	ATC	regulation of RNA export from nucleus	11/6293	12/18723	5.11e-05	3.99e-04	11
GO:006014717	Thyroid	ATC	regulation of posttranscriptional gene silencing	31/6293	52/18723	1.06e-04	7.61e-04	31
GO:006076012	Thyroid	ATC	positive regulation of response to cytokine stimulus	33/6293	57/18723	1.43e-04	9.91e-04	33
GO:006096616	Thyroid	ATC	regulation of gene silencing by RNA	31/6293	53/18723	1.74e-04	1.19e-03	31
GO:006096418	Thyroid	ATC	regulation of gene silencing by miRNA	29/6293	49/18723	2.11e-04	1.39e-03	29
GO:003210324	Thyroid	ATC	positive regulation of response to external stimulus	178/6293	427/18723	2.61e-04	1.67e-03	178
GO:006075912	Thyroid	ATC	regulation of response to cytokine stimulus	76/6293	162/18723	2.92e-04	1.85e-03	76
GO:003223911	Thyroid	ATC	regulation of nucleobase-containing compound transport	12/6293	15/18723	3.10e-04	1.94e-03	12
GO:007135627	Thyroid	ATC	cellular response to tumor necrosis factor	102/6293	229/18723	3.52e-04	2.18e-03	102
GO:005160712	Thyroid	ATC	defense response to virus	115/6293	265/18723	5.31e-04	3.09e-03	115
GO:014054612	Thyroid	ATC	defense response to symbiont	115/6293	265/18723	5.31e-04	3.09e-03	115
GO:190236923	Thyroid	ATC	negative regulation of RNA catabolic process	39/6293	75/18723	7.65e-04	4.23e-03	39
GO:007135912	Thyroid	ATC	cellular response to dsRNA	15/6293	22/18723	9.63e-04	5.13e-03	15
GO:003247913	Thyroid	ATC	regulation of type I interferon production	47/6293	95/18723	9.81e-04	5.21e-03	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

DHX9

SNV

Missense_Mutation

novel

c.1531N>T

p.Asp511Tyr

p.D511Y

Q08211

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A7-A5ZW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

DHX9

SNV

Missense_Mutation

c.2173N>T

p.Val725Phe

p.V725F

Q08211

protein_coding

deleterious(0.04)

probably_damaging(0.998)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DHX9

SNV

Missense_Mutation

c.3280C>T

p.His1094Tyr

p.H1094Y

Q08211

protein_coding

tolerated(1)

benign(0.157)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DHX9

SNV

Missense_Mutation

c.2714G>A

p.Arg905Gln

p.R905Q

Q08211

protein_coding

deleterious(0.02)

probably_damaging(0.984)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DHX9

SNV

Missense_Mutation

novel

c.2202N>C

p.Gln734His

p.Q734H

Q08211

protein_coding

deleterious(0)

probably_damaging(0.95)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DHX9

SNV

Missense_Mutation

rs754675901

c.1582C>T

p.Arg528Cys

p.R528C

Q08211

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DHX9

SNV

Missense_Mutation

c.176G>A

p.Ser59Asn

p.S59N

Q08211

protein_coding

tolerated(0.22)

benign(0.281)

TCGA-BH-A1F0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DHX9

SNV

Missense_Mutation

novel

c.929N>G

p.Leu310Arg

p.L310R

Q08211

protein_coding

deleterious(0.01)

probably_damaging(0.97)

TCGA-C8-A8HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DHX9

SNV

Missense_Mutation

c.2588G>A

p.Arg863His

p.R863H

Q08211

protein_coding

deleterious(0.05)

probably_damaging(0.993)

TCGA-D8-A1JE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamicin

DHX9

SNV

Missense_Mutation

c.67N>G

p.Ile23Val

p.I23V

Q08211

protein_coding

tolerated(0.92)

benign(0.028)

TCGA-E9-A1NI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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