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: DYRK1A

Gene summary for DYRK1A

Gene summary.

Gene information	Species	Human
	Gene symbol	DYRK1A
	Gene ID	1859
	Gene name	dual specificity tyrosine phosphorylation regulated kinase 1A
	Gene Alias	DYRK
	Cytomap	21q22.13
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	Q13627

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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
1859	DYRK1A	CCI_1	Human	Cervix	CC	4.56e-17	1.32e+00	0.528
1859	DYRK1A	CCI_2	Human	Cervix	CC	1.51e-13	1.86e+00	0.5249
1859	DYRK1A	CCI_3	Human	Cervix	CC	6.46e-19	1.30e+00	0.516
1859	DYRK1A	HTA11_3410_2000001011	Human	Colorectum	AD	7.50e-34	-8.55e-01	0.0155
1859	DYRK1A	HTA11_2487_2000001011	Human	Colorectum	SER	1.35e-06	-5.81e-01	-0.1808
1859	DYRK1A	HTA11_2951_2000001011	Human	Colorectum	AD	9.28e-05	-8.21e-01	0.0216
1859	DYRK1A	HTA11_78_2000001011	Human	Colorectum	AD	3.64e-02	-4.23e-01	-0.1088
1859	DYRK1A	HTA11_3361_2000001011	Human	Colorectum	AD	4.82e-13	-7.02e-01	-0.1207
1859	DYRK1A	HTA11_696_2000001011	Human	Colorectum	AD	1.14e-16	-5.71e-01	-0.1464
1859	DYRK1A	HTA11_866_2000001011	Human	Colorectum	AD	8.04e-15	-5.70e-01	-0.1001
1859	DYRK1A	HTA11_5212_2000001011	Human	Colorectum	AD	8.02e-06	-6.60e-01	-0.2061
1859	DYRK1A	HTA11_5216_2000001011	Human	Colorectum	SER	6.25e-06	-5.86e-01	-0.1462
1859	DYRK1A	HTA11_546_2000001011	Human	Colorectum	AD	5.32e-05	-6.20e-01	-0.0842
1859	DYRK1A	HTA11_9341_2000001011	Human	Colorectum	SER	2.85e-02	-7.33e-01	-0.00410000000000005
1859	DYRK1A	HTA11_7862_2000001011	Human	Colorectum	AD	4.64e-10	-8.13e-01	-0.0179
1859	DYRK1A	HTA11_866_3004761011	Human	Colorectum	AD	2.44e-18	-7.20e-01	0.096
1859	DYRK1A	HTA11_4255_2000001011	Human	Colorectum	SER	9.20e-03	-6.60e-01	0.0446
1859	DYRK1A	HTA11_9408_2000001011	Human	Colorectum	AD	1.17e-02	-8.66e-01	0.0451
1859	DYRK1A	HTA11_8622_2000001021	Human	Colorectum	SER	3.31e-06	-6.98e-01	0.0528
1859	DYRK1A	HTA11_10623_2000001011	Human	Colorectum	AD	1.14e-05	-5.38e-01	-0.0177

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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:004677713	Oral cavity	EOLP	protein autophosphorylation	49/2218	227/18723	2.04e-05	3.21e-04	49
GO:200102024	Oral cavity	EOLP	regulation of response to DNA damage stimulus	47/2218	219/18723	3.47e-05	4.85e-04	47
GO:003111321	Oral cavity	EOLP	regulation of microtubule polymerization	18/2218	55/18723	3.72e-05	5.14e-04	18
GO:001063923	Oral cavity	EOLP	negative regulation of organelle organization	67/2218	348/18723	3.78e-05	5.21e-04	67
GO:000762317	Oral cavity	EOLP	circadian rhythm	45/2218	210/18723	5.24e-05	6.79e-04	45
GO:190179626	Oral cavity	EOLP	regulation of signal transduction by p53 class mediator	25/2218	93/18723	5.69e-05	7.24e-04	25
GO:004678521	Oral cavity	EOLP	microtubule polymerization	23/2218	83/18723	6.67e-05	8.27e-04	23
GO:190290424	Oral cavity	EOLP	negative regulation of supramolecular fiber organization	37/2218	167/18723	1.14e-04	1.27e-03	37
GO:004802523	Oral cavity	EOLP	negative regulation of mRNA splicing, via spliceosome	9/2218	20/18723	2.23e-04	2.21e-03	9
GO:007050722	Oral cavity	EOLP	regulation of microtubule cytoskeleton organization	33/2218	148/18723	2.29e-04	2.25e-03	33
GO:003227216	Oral cavity	EOLP	negative regulation of protein polymerization	20/2218	80/18723	8.40e-04	6.56e-03	20
GO:00182121	Oral cavity	EOLP	peptidyl-tyrosine modification	65/2218	378/18723	1.25e-03	9.02e-03	65
GO:000647621	Oral cavity	EOLP	protein deacetylation	23/2218	101/18723	1.42e-03	9.65e-03	23
GO:00181081	Oral cavity	EOLP	peptidyl-tyrosine phosphorylation	64/2218	375/18723	1.65e-03	1.09e-02	64
GO:00311091	Oral cavity	EOLP	microtubule polymerization or depolymerization	26/2218	122/18723	2.01e-03	1.28e-02	26
GO:005068622	Oral cavity	EOLP	negative regulation of mRNA processing	9/2218	29/18723	4.94e-03	2.62e-02	9
GO:005149416	Oral cavity	EOLP	negative regulation of cytoskeleton organization	31/2218	163/18723	5.09e-03	2.67e-02	31
GO:003560121	Oral cavity	EOLP	protein deacylation	23/2218	112/18723	5.70e-03	2.92e-02	23
GO:003111011	Oral cavity	EOLP	regulation of microtubule polymerization or depolymerization	19/2218	88/18723	6.55e-03	3.21e-02	19
GO:009031111	Oral cavity	EOLP	regulation of protein deacetylation	12/2218	48/18723	8.72e-03	4.05e-02	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

DYRK1A

SNV

Missense_Mutation

c.217G>C

p.Asp73His

p.D73H

Q13627

protein_coding

deleterious(0)

benign(0.364)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DYRK1A

SNV

Missense_Mutation

c.1744C>G

p.His582Asp

p.H582D

Q13627

protein_coding

tolerated_low_confidence(0.18)

possibly_damaging(0.84)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DYRK1A

SNV

Missense_Mutation

c.1976N>T

p.Ser659Phe

p.S659F

Q13627

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.962)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DYRK1A

SNV

Missense_Mutation

c.1626C>A

p.Phe542Leu

p.F542L

Q13627

protein_coding

tolerated(0.05)

benign(0.001)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DYRK1A

SNV

Missense_Mutation

c.161N>T

p.Ser54Phe

p.S54F

Q13627

protein_coding

deleterious_low_confidence(0.01)

benign(0.044)

TCGA-AO-A0JC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

DYRK1A

SNV

Missense_Mutation

c.46C>T

p.Arg16Trp

p.R16W

Q13627

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.454)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

DYRK1A

SNV

Missense_Mutation

c.492G>C

p.Leu164Phe

p.L164F

Q13627

protein_coding

deleterious(0.02)

probably_damaging(0.949)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

DYRK1A

SNV

Missense_Mutation

c.2230N>C

p.Asp744His

p.D744H

Q13627

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.99)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DYRK1A

SNV

Missense_Mutation

c.183G>C

p.Gln61His

p.Q61H

Q13627

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.626)

TCGA-D8-A1JP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

DYRK1A

SNV

Missense_Mutation

c.1898A>G

p.Tyr633Cys

p.Y633C

Q13627

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.984)

TCGA-E2-A15E-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
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE		PMID28766366-Compound-Scheme1WO2011135259
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE		PMID28766366-Compound-Scheme15-1
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE		PMID28766366-Compound-Scheme6Pyrrolo[2,3-d]pyrimidines
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE		PMID28766366-Compound-Scheme23MPPDerivatives
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE	inhibitor	249565842
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE		PMID28766366-Compound-Scheme13INDY
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE	inhibitor	405560505
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE		PMID28766366-Compound-Scheme4Upper
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE		PMID28766366-Compound-Scheme12-3
1859	DYRK1A	DRUGGABLE GENOME, KINASE, ENZYME, TYROSINE KINASE, SERINE THREONINE KINASE		PMID28766366-Compound-Scheme18

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