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: DDR1

Gene summary for DDR1

Gene summary.

Gene information	Species	Human
	Gene symbol	DDR1
	Gene ID	780
	Gene name	discoidin domain receptor tyrosine kinase 1
	Gene Alias	CAK
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q08345

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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
780	DDR1	HTA11_3410_2000001011	Human	Colorectum	AD	3.19e-12	3.20e-01	0.0155
780	DDR1	HTA11_2487_2000001011	Human	Colorectum	SER	2.77e-26	8.34e-01	-0.1808
780	DDR1	HTA11_2951_2000001011	Human	Colorectum	AD	1.13e-03	3.98e-01	0.0216
780	DDR1	HTA11_1938_2000001011	Human	Colorectum	AD	1.83e-27	1.07e+00	-0.0811
780	DDR1	HTA11_78_2000001011	Human	Colorectum	AD	3.35e-25	8.03e-01	-0.1088
780	DDR1	HTA11_347_2000001011	Human	Colorectum	AD	1.82e-54	1.10e+00	-0.1954
780	DDR1	HTA11_411_2000001011	Human	Colorectum	SER	8.78e-14	1.31e+00	-0.2602
780	DDR1	HTA11_2112_2000001011	Human	Colorectum	SER	1.77e-15	1.28e+00	-0.2196
780	DDR1	HTA11_3361_2000001011	Human	Colorectum	AD	2.78e-13	5.15e-01	-0.1207
780	DDR1	HTA11_83_2000001011	Human	Colorectum	SER	6.88e-14	7.87e-01	-0.1526
780	DDR1	HTA11_696_2000001011	Human	Colorectum	AD	8.96e-40	9.80e-01	-0.1464
780	DDR1	HTA11_866_2000001011	Human	Colorectum	AD	8.83e-25	7.00e-01	-0.1001
780	DDR1	HTA11_1391_2000001011	Human	Colorectum	AD	1.58e-30	1.04e+00	-0.059
780	DDR1	HTA11_2992_2000001011	Human	Colorectum	SER	1.39e-03	7.07e-01	-0.1706
780	DDR1	HTA11_5212_2000001011	Human	Colorectum	AD	1.08e-11	7.10e-01	-0.2061
780	DDR1	HTA11_5216_2000001011	Human	Colorectum	SER	2.00e-05	6.57e-01	-0.1462
780	DDR1	HTA11_546_2000001011	Human	Colorectum	AD	2.38e-07	5.53e-01	-0.0842
780	DDR1	HTA11_7862_2000001011	Human	Colorectum	AD	1.20e-13	7.94e-01	-0.0179
780	DDR1	HTA11_866_3004761011	Human	Colorectum	AD	5.68e-38	9.01e-01	0.096
780	DDR1	HTA11_4255_2000001011	Human	Colorectum	SER	8.83e-04	5.54e-01	0.0446

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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
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:0048732	Colorectum	AD	gland development	149/3918	436/18723	6.07e-11	6.33e-09	149
GO:0022411	Colorectum	AD	cellular component disassembly	147/3918	443/18723	8.53e-10	6.76e-08	147
GO:0010810	Colorectum	AD	regulation of cell-substrate adhesion	81/3918	221/18723	4.80e-08	2.55e-06	81
GO:0031589	Colorectum	AD	cell-substrate adhesion	116/3918	363/18723	4.68e-07	1.76e-05	116
GO:0030879	Colorectum	AD	mammary gland development	53/3918	137/18723	1.46e-06	4.58e-05	53
GO:0001952	Colorectum	AD	regulation of cell-matrix adhesion	50/3918	128/18723	2.05e-06	6.05e-05	50
GO:0042060	Colorectum	AD	wound healing	128/3918	422/18723	2.73e-06	7.89e-05	128
GO:0016049	Colorectum	AD	cell growth	143/3918	482/18723	2.83e-06	8.09e-05	143
GO:0001558	Colorectum	AD	regulation of cell growth	124/3918	414/18723	7.67e-06	1.86e-04	124
GO:0046777	Colorectum	AD	protein autophosphorylation	74/3918	227/18723	2.48e-05	4.76e-04	74
GO:0007160	Colorectum	AD	cell-matrix adhesion	75/3918	233/18723	3.56e-05	6.45e-04	75
GO:0061564	Colorectum	AD	axon development	132/3918	467/18723	8.40e-05	1.31e-03	132
GO:0061180	Colorectum	AD	mammary gland epithelium development	28/3918	67/18723	8.74e-05	1.35e-03	28
GO:0033674	Colorectum	AD	positive regulation of kinase activity	131/3918	467/18723	1.28e-04	1.85e-03	131
GO:0022612	Colorectum	AD	gland morphogenesis	42/3918	118/18723	1.62e-04	2.23e-03	42
GO:0050878	Colorectum	AD	regulation of body fluid levels	108/3918	379/18723	2.54e-04	3.20e-03	108
GO:0060562	Colorectum	AD	epithelial tube morphogenesis	93/3918	325/18723	5.65e-04	6.00e-03	93
GO:0007589	Colorectum	AD	body fluid secretion	33/3918	93/18723	8.26e-04	8.13e-03	33
GO:0060443	Colorectum	AD	mammary gland morphogenesis	18/3918	43/18723	1.51e-03	1.27e-02	18
GO:0048588	Colorectum	AD	developmental cell growth	67/3918	234/18723	3.03e-03	2.25e-02	67

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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

DDR1

SNV

Missense_Mutation

c.1852N>C

p.Glu618Gln

p.E618Q

Q08345

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

DDR1

SNV

Missense_Mutation

rs527938479

c.1826N>A

p.Arg609Gln

p.R609Q

Q08345

protein_coding

tolerated(0.69)

benign(0.019)

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

DDR1

SNV

Missense_Mutation

novel

c.1438G>A

p.Glu480Lys

p.E480K

Q08345

protein_coding

tolerated(0.82)

benign(0.291)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DDR1

SNV

Missense_Mutation

rs370113205

c.1696N>A

p.Val566Ile

p.V566I

Q08345

protein_coding

tolerated(0.06)

probably_damaging(0.964)

TCGA-D8-A1X6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

DDR1

SNV

Missense_Mutation

novel

c.571C>T

p.Leu191Phe

p.L191F

Q08345

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-E2-A574-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DDR1

deletion

Frame_Shift_Del

novel

c.949delN

p.Met318CysfsTer5

p.M318Cfs*5

Q08345

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

DDR1

SNV

Missense_Mutation

rs557271556

c.586G>A

p.Ala196Thr

p.A196T

Q08345

protein_coding

tolerated(0.09)

benign(0.192)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DDR1

SNV

Missense_Mutation

rs370297461

c.2282G>A

p.Arg761His

p.R761H

Q08345

protein_coding

deleterious(0)

probably_damaging(0.91)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DDR1

SNV

Missense_Mutation

novel

c.2569G>A

p.Glu857Lys

p.E857K

Q08345

protein_coding

deleterious(0)

possibly_damaging(0.699)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DDR1

SNV

Missense_Mutation

rs776556090

c.2648N>T

p.Pro883Leu

p.P883L

Q08345

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A2LV-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
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE	inhibitor	381118865
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE		US9567304, Compound N-9
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE		VAPBGCRAUJRZPO-UHFFFAOYSA-N
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE		BDBM50080408
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE		US9695118, 4
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE		NG7
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE	inhibitor	328083456
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE	inhibitor	178102314	IMATINIB
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE	inhibitor	252827391
780	DDR1	DRUGGABLE GENOME, KINASE, TYROSINE KINASE, CLINICALLY ACTIONABLE	inhibitor	363894135	MERESTINIB

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