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: DDX58

Gene summary for DDX58

Gene summary.

Gene information	Species	Human
	Gene symbol	DDX58
	Gene ID	23586
	Gene name	DExD/H-box helicase 58
	Gene Alias	RIG-I
	Cytomap	9p21.1
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	O95786

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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
23586	DDX58	CCI_2	Human	Cervix	CC	3.65e-12	1.94e+00	0.5249
23586	DDX58	CCI_3	Human	Cervix	CC	1.53e-03	5.44e-01	0.516
23586	DDX58	HTA11_347_2000001011	Human	Colorectum	AD	2.79e-07	3.08e-01	-0.1954
23586	DDX58	HTA11_99999970781_79442	Human	Colorectum	MSS	4.98e-02	2.30e-01	0.294
23586	DDX58	HTA11_99999965062_69753	Human	Colorectum	MSI-H	2.98e-06	1.18e+00	0.3487
23586	DDX58	LZE4T	Human	Esophagus	ESCC	6.43e-06	2.82e-01	0.0811
23586	DDX58	LZE5T	Human	Esophagus	ESCC	2.36e-09	4.97e-01	0.0514
23586	DDX58	LZE7T	Human	Esophagus	ESCC	1.91e-03	3.17e-01	0.0667
23586	DDX58	LZE20T	Human	Esophagus	ESCC	7.63e-07	2.64e-01	0.0662
23586	DDX58	LZE21D1	Human	Esophagus	HGIN	1.60e-04	7.60e-01	0.0632
23586	DDX58	LZE24T	Human	Esophagus	ESCC	3.23e-18	6.91e-01	0.0596
23586	DDX58	LZE21T	Human	Esophagus	ESCC	1.94e-05	5.68e-01	0.0655
23586	DDX58	LZE6T	Human	Esophagus	ESCC	3.20e-02	1.71e-01	0.0845
23586	DDX58	P1T-E	Human	Esophagus	ESCC	3.45e-13	7.96e-01	0.0875
23586	DDX58	P2T-E	Human	Esophagus	ESCC	1.24e-49	9.23e-01	0.1177
23586	DDX58	P4T-E	Human	Esophagus	ESCC	4.65e-07	3.11e-01	0.1323
23586	DDX58	P5T-E	Human	Esophagus	ESCC	5.12e-31	1.08e+00	0.1327
23586	DDX58	P8T-E	Human	Esophagus	ESCC	3.52e-19	3.61e-01	0.0889
23586	DDX58	P9T-E	Human	Esophagus	ESCC	5.12e-34	8.86e-01	0.1131
23586	DDX58	P11T-E	Human	Esophagus	ESCC	2.01e-25	9.48e-01	0.1426

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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
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:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:00018197	Cervix	CC	positive regulation of cytokine production	95/2311	467/18723	4.88e-07	1.85e-05	95
GO:00305229	Cervix	CC	intracellular receptor signaling pathway	60/2311	265/18723	1.89e-06	5.97e-05	60
GO:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:00028315	Cervix	CC	regulation of response to biotic stimulus	67/2311	327/18723	1.79e-05	3.36e-04	67
GO:00096158	Cervix	CC	response to virus	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:00022212	Cervix	CC	pattern recognition receptor signaling pathway	39/2311	172/18723	1.08e-04	1.38e-03	39
GO:00027534	Cervix	CC	cytoplasmic pattern recognition receptor signaling pathway	18/2311	60/18723	2.26e-04	2.55e-03	18
GO:00510915	Cervix	CC	positive regulation of DNA-binding transcription factor activity	51/2311	260/18723	5.05e-04	4.92e-03	51
GO:00395292	Cervix	CC	RIG-I signaling pathway	10/2311	27/18723	9.25e-04	7.84e-03	10
GO:00026973	Cervix	CC	regulation of immune effector process	62/2311	339/18723	9.25e-04	7.84e-03	62
GO:00027201	Cervix	CC	positive regulation of cytokine production involved in immune response	17/2311	65/18723	1.84e-03	1.37e-02	17
GO:00985863	Cervix	CC	cellular response to virus	20/2311	84/18723	2.62e-03	1.81e-02	20
GO:0002443	Cervix	CC	leukocyte mediated immunity	73/2311	440/18723	5.01e-03	2.98e-02	73
GO:0002699	Cervix	CC	positive regulation of immune effector process	43/2311	235/18723	5.13e-03	3.02e-02	43
GO:00324791	Cervix	CC	regulation of type I interferon production	21/2311	95/18723	5.32e-03	3.10e-02	21
GO:00326061	Cervix	CC	type I interferon production	21/2311	95/18723	5.32e-03	3.10e-02	21
GO:00395281	Cervix	CC	cytoplasmic pattern recognition receptor signaling pathway in response to virus	10/2311	34/18723	6.40e-03	3.58e-02	10
GO:00607602	Cervix	CC	positive regulation of response to cytokine stimulus	14/2311	57/18723	8.17e-03	4.25e-02	14
GO:00324815	Cervix	CC	positive regulation of type I interferon production	14/2311	58/18723	9.57e-03	4.73e-02	14

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517120	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa0516920	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0516414	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa05171110	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa05169110	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0516415	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa05171	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa05160	Colorectum	AD	Hepatitis C	54/2092	157/8465	3.87e-03	1.96e-02	1.25e-02	54
hsa051711	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa051601	Colorectum	AD	Hepatitis C	54/2092	157/8465	3.87e-03	1.96e-02	1.25e-02	54
hsa051714	Colorectum	MSS	Coronavirus disease - COVID-19	108/1875	232/8465	6.50e-17	1.67e-15	1.03e-15	108
hsa051602	Colorectum	MSS	Hepatitis C	52/1875	157/8465	9.29e-04	5.58e-03	3.42e-03	52
hsa05169	Colorectum	MSS	Epstein-Barr virus infection	63/1875	202/8465	1.63e-03	8.98e-03	5.50e-03	63
hsa05161	Colorectum	MSS	Hepatitis B	48/1875	162/8465	1.53e-02	4.93e-02	3.02e-02	48
hsa051715	Colorectum	MSS	Coronavirus disease - COVID-19	108/1875	232/8465	6.50e-17	1.67e-15	1.03e-15	108
hsa051603	Colorectum	MSS	Hepatitis C	52/1875	157/8465	9.29e-04	5.58e-03	3.42e-03	52
hsa051691	Colorectum	MSS	Epstein-Barr virus infection	63/1875	202/8465	1.63e-03	8.98e-03	5.50e-03	63
hsa051611	Colorectum	MSS	Hepatitis B	48/1875	162/8465	1.53e-02	4.93e-02	3.02e-02	48
hsa051716	Colorectum	MSI-H	Coronavirus disease - COVID-19	91/797	232/8465	2.21e-35	3.58e-33	3.00e-33	91
hsa051717	Colorectum	MSI-H	Coronavirus disease - COVID-19	91/797	232/8465	2.21e-35	3.58e-33	3.00e-33	91

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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

DDX58

SNV

Missense_Mutation

c.2549N>A

p.Pro850Gln

p.P850Q

O95786

protein_coding

deleterious(0.02)

possibly_damaging(0.596)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

DDX58

SNV

Missense_Mutation

c.2356N>T

p.His786Tyr

p.H786Y

O95786

protein_coding

deleterious(0.01)

benign(0.063)

TCGA-A2-A25D-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

DDX58

SNV

Missense_Mutation

novel

c.2251N>A

p.Glu751Lys

p.E751K

O95786

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-AC-A2QI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

DDX58

SNV

Missense_Mutation

c.1313N>C

p.Val438Ala

p.V438A

O95786

protein_coding

tolerated(0.28)

benign(0.031)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

DDX58

insertion

Frame_Shift_Ins

novel

c.2532_2533insCCCTGGGCTTCTCTCTCTTCTAGTTCTATTCTAGTCTTTTTTTA

p.Arg845ProfsTer15

p.R845Pfs*15

O95786

protein_coding

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DDX58

deletion

Frame_Shift_Del

novel

c.2560delN

p.Ser854GlnfsTer24

p.S854Qfs*24

O95786

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

DDX58

SNV

Missense_Mutation

novel

c.1047N>T

p.Gln349His

p.Q349H

O95786

protein_coding

deleterious(0.05)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DDX58

SNV

Missense_Mutation

novel

c.2245N>C

p.Glu749Gln

p.E749Q

O95786

protein_coding

deleterious(0.02)

benign(0.235)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

DDX58

SNV

Missense_Mutation

c.1447G>A

p.Glu483Lys

p.E483K

O95786

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-JW-A5VJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DDX58

SNV

Missense_Mutation

novel

c.63N>G

p.Asp21Glu

p.D21E

O95786

protein_coding

tolerated(0.14)

benign(0.23)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

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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