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: DDX21

Gene summary for DDX21

Gene summary.

Gene information	Species	Human
	Gene symbol	DDX21
	Gene ID	9188
	Gene name	DExD-box helicase 21
	Gene Alias	GUA
	Cytomap	10q22.1
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	Q9NR30

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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
9188	DDX21	HTA11_866_2000001011	Human	Colorectum	AD	8.03e-05	-2.38e-01	-0.1001
9188	DDX21	HTA11_99999965104_69814	Human	Colorectum	MSS	2.89e-13	1.01e+00	0.281
9188	DDX21	HTA11_99999971662_82457	Human	Colorectum	MSS	9.39e-08	7.44e-01	0.3859
9188	DDX21	A002-C-010	Human	Colorectum	FAP	6.54e-04	-2.31e-01	0.242
9188	DDX21	A015-C-203	Human	Colorectum	FAP	1.85e-20	-4.17e-01	-0.1294
9188	DDX21	A002-C-201	Human	Colorectum	FAP	2.06e-07	-2.99e-01	0.0324
9188	DDX21	A002-C-203	Human	Colorectum	FAP	1.46e-02	-2.13e-01	0.2786
9188	DDX21	A001-C-108	Human	Colorectum	FAP	2.35e-06	4.06e-02	-0.0272
9188	DDX21	A002-C-205	Human	Colorectum	FAP	3.55e-10	-2.59e-02	-0.1236
9188	DDX21	A015-C-006	Human	Colorectum	FAP	7.43e-05	4.39e-02	-0.0994
9188	DDX21	A015-C-106	Human	Colorectum	FAP	4.36e-05	8.19e-02	-0.0511
9188	DDX21	A002-C-114	Human	Colorectum	FAP	4.44e-07	-2.16e-01	-0.1561
9188	DDX21	A015-C-104	Human	Colorectum	FAP	2.84e-15	-1.80e-01	-0.1899
9188	DDX21	A001-C-014	Human	Colorectum	FAP	1.23e-06	1.60e-02	0.0135
9188	DDX21	A002-C-016	Human	Colorectum	FAP	3.55e-12	-1.95e-01	0.0521
9188	DDX21	A015-C-002	Human	Colorectum	FAP	3.30e-03	-1.82e-01	-0.0763
9188	DDX21	A001-C-203	Human	Colorectum	FAP	2.75e-05	-3.06e-02	-0.0481
9188	DDX21	A002-C-116	Human	Colorectum	FAP	3.99e-18	-2.30e-01	-0.0452
9188	DDX21	A014-C-008	Human	Colorectum	FAP	9.42e-06	6.15e-02	-0.191
9188	DDX21	A018-E-020	Human	Colorectum	FAP	2.30e-08	-3.30e-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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:0022613	Colorectum	AD	ribonucleoprotein complex biogenesis	151/3918	463/18723	1.96e-09	1.39e-07	151
GO:0043123	Colorectum	AD	positive regulation of I-kappaB kinase/NF-kappaB signaling	60/3918	186/18723	1.91e-04	2.56e-03	60
GO:0043122	Colorectum	AD	regulation of I-kappaB kinase/NF-kappaB signaling	76/3918	249/18723	2.17e-04	2.85e-03	76
GO:0001649	Colorectum	AD	osteoblast differentiation	70/3918	229/18723	3.59e-04	4.18e-03	70
GO:0007249	Colorectum	AD	I-kappaB kinase/NF-kappaB signaling	82/3918	281/18723	6.09e-04	6.40e-03	82
GO:0042254	Colorectum	AD	ribosome biogenesis	84/3918	299/18723	1.82e-03	1.50e-02	84
GO:0001503	Colorectum	AD	ossification	106/3918	408/18723	7.68e-03	4.64e-02	106
GO:00226132	Colorectum	MSS	ribonucleoprotein complex biogenesis	144/3467	463/18723	2.76e-11	3.67e-09	144
GO:00431221	Colorectum	MSS	regulation of I-kappaB kinase/NF-kappaB signaling	71/3467	249/18723	7.12e-05	1.21e-03	71
GO:00072491	Colorectum	MSS	I-kappaB kinase/NF-kappaB signaling	77/3467	281/18723	1.51e-04	2.19e-03	77
GO:00431231	Colorectum	MSS	positive regulation of I-kappaB kinase/NF-kappaB signaling	55/3467	186/18723	1.60e-04	2.29e-03	55
GO:00016492	Colorectum	MSS	osteoblast differentiation	64/3467	229/18723	2.91e-04	3.83e-03	64
GO:00422542	Colorectum	MSS	ribosome biogenesis	79/3467	299/18723	4.32e-04	5.23e-03	79
GO:0006364	Colorectum	MSS	rRNA processing	58/3467	225/18723	4.17e-03	3.03e-02	58
GO:0016072	Colorectum	MSS	rRNA metabolic process	60/3467	236/18723	5.01e-03	3.46e-02	60
GO:00015032	Colorectum	MSS	ossification	96/3467	408/18723	6.09e-03	4.07e-02	96
GO:00431222	Colorectum	FAP	regulation of I-kappaB kinase/NF-kappaB signaling	56/2622	249/18723	1.82e-04	2.69e-03	56
GO:00226134	Colorectum	FAP	ribonucleoprotein complex biogenesis	91/2622	463/18723	4.28e-04	5.12e-03	91
GO:00016493	Colorectum	FAP	osteoblast differentiation	51/2622	229/18723	4.40e-04	5.22e-03	51
GO:00431232	Colorectum	FAP	positive regulation of I-kappaB kinase/NF-kappaB signaling	42/2622	186/18723	1.01e-03	9.89e-03	42

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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

DDX21

SNV

Missense_Mutation

c.1756N>A

p.Val586Met

p.V586M

Q9NR30

protein_coding

deleterious(0.01)

possibly_damaging(0.646)

TCGA-AO-A03P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

DDX21

SNV

Missense_Mutation

rs780033357

c.2113N>G

p.Leu705Val

p.L705V

Q9NR30

protein_coding

deleterious(0.04)

probably_damaging(0.955)

TCGA-BH-A0HO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

DDX21

SNV

Missense_Mutation

c.526N>C

p.Glu176Gln

p.E176Q

Q9NR30

protein_coding

deleterious(0.02)

benign(0.005)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

DDX21

SNV

Missense_Mutation

rs868785299

c.1784A>G

p.Lys595Arg

p.K595R

Q9NR30

protein_coding

tolerated(0.73)

benign(0.009)

TCGA-BH-A201-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDX21

SNV

Missense_Mutation

rs766890848

c.1873N>A

p.Asp625Asn

p.D625N

Q9NR30

protein_coding

deleterious(0.02)

possibly_damaging(0.484)

TCGA-C8-A12K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DDX21

SNV

Missense_Mutation

c.1161G>C

p.Lys387Asn

p.K387N

Q9NR30

protein_coding

deleterious(0.04)

benign(0.248)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDX21

SNV

Missense_Mutation

novel

c.1209N>C

p.Lys403Asn

p.K403N

Q9NR30

protein_coding

tolerated(0.08)

benign(0.003)

TCGA-E2-A574-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DDX21

SNV

Missense_Mutation

c.692N>A

p.Arg231Gln

p.R231Q

Q9NR30

protein_coding

deleterious(0.01)

possibly_damaging(0.826)

TCGA-GM-A2DF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

DDX21

insertion

Frame_Shift_Ins

novel

c.1897_1898insG

p.Asn633ArgfsTer14

p.N633Rfs*14

Q9NR30

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

DDX21

insertion

Frame_Shift_Ins

novel

c.1898_1899insGACGGAGTTTCTTAAAATGATTGTG

p.Asn633LysfsTer22

p.N633Kfs*22

Q9NR30

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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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