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: DDX17

Gene summary for DDX17

Gene summary.

Gene information	Species	Human
	Gene symbol	DDX17
	Gene ID	10521
	Gene name	DEAD-box helicase 17
	Gene Alias	P72
	Cytomap	22q13.1
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	A0A1W2PQ51

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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
10521	DDX17	GSM4909285	Human	Breast	IDC	2.04e-04	-2.33e-01	0.21
10521	DDX17	GSM4909293	Human	Breast	IDC	4.72e-05	1.97e-01	0.1581
10521	DDX17	GSM4909294	Human	Breast	IDC	5.48e-05	-2.64e-01	0.2022
10521	DDX17	GSM4909296	Human	Breast	IDC	9.31e-14	-3.51e-01	0.1524
10521	DDX17	GSM4909297	Human	Breast	IDC	5.48e-18	-3.24e-01	0.1517
10521	DDX17	GSM4909308	Human	Breast	IDC	1.51e-03	1.42e-01	0.158
10521	DDX17	GSM4909311	Human	Breast	IDC	2.38e-38	-4.19e-01	0.1534
10521	DDX17	GSM4909312	Human	Breast	IDC	2.38e-12	-2.12e-01	0.1552
10521	DDX17	GSM4909313	Human	Breast	IDC	2.00e-04	2.14e-01	0.0391
10521	DDX17	GSM4909316	Human	Breast	IDC	3.66e-07	-6.42e-01	0.21
10521	DDX17	GSM4909319	Human	Breast	IDC	1.34e-44	-5.54e-01	0.1563
10521	DDX17	GSM4909320	Human	Breast	IDC	3.66e-11	-6.33e-01	0.1575
10521	DDX17	GSM4909321	Human	Breast	IDC	8.37e-29	-5.75e-01	0.1559
10521	DDX17	brca1	Human	Breast	Precancer	8.32e-07	-4.12e-01	-0.0338
10521	DDX17	brca10	Human	Breast	Precancer	3.26e-04	-4.03e-01	-0.0029
10521	DDX17	M1	Human	Breast	IDC	4.93e-10	4.86e-01	0.1577
10521	DDX17	M5	Human	Breast	IDC	1.36e-07	5.38e-01	0.1598
10521	DDX17	NCCBC14	Human	Breast	DCIS	3.54e-15	-7.94e-02	0.2021
10521	DDX17	NCCBC2	Human	Breast	DCIS	9.73e-04	1.38e-01	0.1554
10521	DDX17	NCCBC3	Human	Breast	DCIS	2.22e-07	2.16e-01	0.1198

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:0035914	Breast	Precancer	skeletal muscle cell differentiation	11/1080	67/18723	1.47e-03	1.52e-02	11
GO:00018373	Breast	Precancer	epithelial to mesenchymal transition	19/1080	157/18723	1.78e-03	1.75e-02	19
GO:00305228	Breast	Precancer	intracellular receptor signaling pathway	27/1080	265/18723	2.99e-03	2.57e-02	27
GO:00605374	Breast	Precancer	muscle tissue development	37/1080	403/18723	3.60e-03	2.98e-02	37
GO:00147063	Breast	Precancer	striated muscle tissue development	35/1080	384/18723	5.10e-03	3.83e-02	35
GO:00434018	Breast	Precancer	steroid hormone mediated signaling pathway	16/1080	136/18723	5.21e-03	3.88e-02	16
GO:004854514	Breast	IDC	response to steroid hormone	70/1434	339/18723	1.34e-14	4.23e-12	70
GO:002261314	Breast	IDC	ribonucleoprotein complex biogenesis	83/1434	463/18723	2.01e-13	5.20e-11	83
GO:000838014	Breast	IDC	RNA splicing	73/1434	434/18723	1.27e-10	1.57e-08	73
GO:004348414	Breast	IDC	regulation of RNA splicing	36/1434	148/18723	3.32e-10	3.77e-08	36
GO:000037514	Breast	IDC	RNA splicing, via transesterification reactions	58/1434	324/18723	9.44e-10	9.58e-08	58
GO:000037714	Breast	IDC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:000039814	Breast	IDC	mRNA splicing, via spliceosome	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:004225414	Breast	IDC	ribosome biogenesis	52/1434	299/18723	1.90e-08	1.32e-06	52
GO:004802414	Breast	IDC	regulation of mRNA splicing, via spliceosome	23/1434	101/18723	1.74e-06	7.28e-05	23
GO:007138314	Breast	IDC	cellular response to steroid hormone stimulus	35/1434	204/18723	5.29e-06	1.75e-04	35
GO:000636414	Breast	IDC	rRNA processing	35/1434	225/18723	4.59e-05	1.03e-03	35
GO:001607214	Breast	IDC	rRNA metabolic process	36/1434	236/18723	5.48e-05	1.17e-03	36
GO:003051813	Breast	IDC	intracellular steroid hormone receptor signaling pathway	22/1434	116/18723	6.16e-05	1.28e-03	22
GO:003052113	Breast	IDC	androgen receptor signaling pathway	12/1434	44/18723	8.17e-05	1.60e-03	12

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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

DDX17

SNV

Missense_Mutation

novel

c.793N>T

p.Asp265Tyr

p.D265Y

protein_coding

tolerated(0.78)

benign(0.018)

TCGA-A2-A0ER-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

DDX17

SNV

Missense_Mutation

novel

c.1427N>G

p.Asp476Gly

p.D476G

protein_coding

deleterious(0)

probably_damaging(0.916)

TCGA-AQ-A7U7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Targeted Molecular therapy

rituximab

DDX17

SNV

Missense_Mutation

c.1262C>A

p.Thr421Lys

p.T421K

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0H3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDX17

SNV

Missense_Mutation

c.815N>C

p.Arg272Thr

p.R272T

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-BH-A1FC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DDX17

SNV

Missense_Mutation

rs762058898

c.1963N>G

p.Gln655Glu

p.Q655E

protein_coding

tolerated_low_confidence(0.14)

benign(0.014)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DDX17

insertion

Frame_Shift_Ins

novel

c.1168_1169insAGCTT

p.Ile390LysfsTer6

p.I390Kfs*6

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

DDX17

insertion

In_Frame_Ins

novel

c.1166_1167insAACAAAACAAAACTTAGC

p.Asn389delinsLysThrLysGlnAsnLeuAla

p.N389delinsKTKQNLA

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

DDX17

insertion

Frame_Shift_Ins

novel

c.946_947insAG

p.Leu316GlnfsTer39

p.L316Qfs*39

protein_coding

TCGA-A8-A07O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

DDX17

insertion

Nonsense_Mutation

novel

c.945_946insTTGAAATTTTAACATGGTTATGTAAA

p.Arg317LysfsTer3

p.R317Kfs*3

protein_coding

TCGA-A8-A07O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

DDX17

insertion

Nonsense_Mutation

novel

c.942_943insTTGTTGGTCATGTTTTCAGGTTGATCCAACTAATGG

p.Thr314_Asn315insLeuLeuValMetPheSerGlyTerSerAsnTerTrp

p.T314_N315insLLVMFSG*SN*W

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

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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