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: DYRK2

Gene summary for DYRK2

Gene summary.

Gene information	Species	Human
	Gene symbol	DYRK2
	Gene ID	8445
	Gene name	dual specificity tyrosine phosphorylation regulated kinase 2
	Gene Alias	DYRK2
	Cytomap	12q15
	Gene Type	protein-coding
	GO ID	GO:0000271
	UniProtAcc	Q92630

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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
8445	DYRK2	HCC1_Meng	Human	Liver	HCC	8.75e-48	-7.58e-04	0.0246
8445	DYRK2	HCC2_Meng	Human	Liver	HCC	1.32e-32	1.70e-01	0.0107
8445	DYRK2	cirrhotic2	Human	Liver	Cirrhotic	3.59e-04	4.83e-02	0.0201
8445	DYRK2	HCC1	Human	Liver	HCC	1.57e-06	3.61e+00	0.5336
8445	DYRK2	HCC2	Human	Liver	HCC	9.13e-10	3.16e+00	0.5341
8445	DYRK2	S014	Human	Liver	HCC	5.29e-19	6.72e-01	0.2254
8445	DYRK2	S015	Human	Liver	HCC	5.46e-14	6.16e-01	0.2375
8445	DYRK2	S016	Human	Liver	HCC	5.26e-26	8.34e-01	0.2243
8445	DYRK2	S027	Human	Liver	HCC	6.10e-09	6.89e-01	0.2446
8445	DYRK2	S028	Human	Liver	HCC	7.84e-15	5.49e-01	0.2503
8445	DYRK2	S029	Human	Liver	HCC	1.26e-10	3.78e-01	0.2581
8445	DYRK2	male-WTA	Human	Thyroid	PTC	3.79e-16	1.72e-01	0.1037
8445	DYRK2	PTC01	Human	Thyroid	PTC	9.60e-03	5.99e-02	0.1899
8445	DYRK2	PTC04	Human	Thyroid	PTC	4.21e-05	8.86e-02	0.1927
8445	DYRK2	PTC05	Human	Thyroid	PTC	7.29e-06	2.83e-01	0.2065
8445	DYRK2	PTC06	Human	Thyroid	PTC	1.91e-12	3.95e-01	0.2057
8445	DYRK2	PTC07	Human	Thyroid	PTC	3.45e-17	1.54e-01	0.2044
8445	DYRK2	ATC09	Human	Thyroid	ATC	8.81e-03	1.17e-01	0.2871
8445	DYRK2	ATC12	Human	Thyroid	ATC	1.34e-10	1.78e-01	0.34
8445	DYRK2	ATC13	Human	Thyroid	ATC	6.11e-35	6.57e-01	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
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:000609112	Liver	Cirrhotic	generation of precursor metabolites and energy	238/4634	490/18723	6.85e-31	1.07e-27	238
GO:001598012	Liver	Cirrhotic	energy derivation by oxidation of organic compounds	154/4634	318/18723	3.11e-20	8.87e-18	154
GO:009719312	Liver	Cirrhotic	intrinsic apoptotic signaling pathway	130/4634	288/18723	2.69e-14	2.45e-12	130
GO:000599612	Liver	Cirrhotic	monosaccharide metabolic process	104/4634	257/18723	1.74e-08	6.32e-07	104
GO:001931812	Liver	Cirrhotic	hexose metabolic process	97/4634	237/18723	2.67e-08	9.16e-07	97
GO:000600611	Liver	Cirrhotic	glucose metabolic process	82/4634	196/18723	1.01e-07	2.93e-06	82
GO:006201212	Liver	Cirrhotic	regulation of small molecule metabolic process	124/4634	334/18723	2.74e-07	6.79e-06	124
GO:004346712	Liver	Cirrhotic	regulation of generation of precursor metabolites and energy	58/4634	130/18723	5.81e-07	1.28e-05	58
GO:007233112	Liver	Cirrhotic	signal transduction by p53 class mediator	69/4634	163/18723	5.97e-07	1.30e-05	69
GO:00723326	Liver	Cirrhotic	intrinsic apoptotic signaling pathway by p53 class mediator	38/4634	76/18723	1.75e-06	3.32e-05	38
GO:000610911	Liver	Cirrhotic	regulation of carbohydrate metabolic process	70/4634	178/18723	1.14e-05	1.62e-04	70
GO:00086306	Liver	Cirrhotic	intrinsic apoptotic signaling pathway in response to DNA damage	42/4634	99/18723	8.44e-05	9.17e-04	42
GO:00427716	Liver	Cirrhotic	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	22/4634	43/18723	1.69e-04	1.59e-03	22
GO:004426211	Liver	Cirrhotic	cellular carbohydrate metabolic process	97/4634	283/18723	1.89e-04	1.76e-03	97
GO:00160511	Liver	Cirrhotic	carbohydrate biosynthetic process	73/4634	202/18723	1.91e-04	1.77e-03	73
GO:00109061	Liver	Cirrhotic	regulation of glucose metabolic process	47/4634	119/18723	2.61e-04	2.33e-03	47
GO:00106751	Liver	Cirrhotic	regulation of cellular carbohydrate metabolic process	54/4634	146/18723	6.53e-04	4.96e-03	54
GO:190179612	Liver	Cirrhotic	regulation of signal transduction by p53 class mediator	37/4634	93/18723	9.58e-04	6.78e-03	37
GO:00059771	Liver	Cirrhotic	glycogen metabolic process	30/4634	72/18723	1.18e-03	7.98e-03	30
GO:00060731	Liver	Cirrhotic	cellular glucan metabolic process	30/4634	73/18723	1.53e-03	9.99e-03	30

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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

DYRK2

SNV

Missense_Mutation

c.1133G>T

p.Arg378Leu

p.R378L

Q92630

protein_coding

deleterious(0)

probably_damaging(0.933)

TCGA-A2-A0SV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate therapy

zometa

DYRK2

SNV

Missense_Mutation

rs773264334

c.1592N>A

p.Arg531Gln

p.R531Q

Q92630

protein_coding

tolerated(0.15)

probably_damaging(0.964)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DYRK2

SNV

Missense_Mutation

c.1520T>C

p.Leu507Pro

p.L507P

Q92630

protein_coding

deleterious(0.02)

possibly_damaging(0.899)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DYRK2

SNV

Missense_Mutation

rs756215589

c.70N>T

p.Val24Phe

p.V24F

Q92630

protein_coding

tolerated_low_confidence(0.21)

benign(0.011)

TCGA-BH-A203-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DYRK2

SNV

Missense_Mutation

c.271N>G

p.Gln91Glu

p.Q91E

Q92630

protein_coding

tolerated_low_confidence(0.61)

benign(0.003)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DYRK2

insertion

In_Frame_Ins

novel

c.1766_1767insAGATATAGAAGATGGTCGTTTCTTGTCAGTCTCGTTAGTTTTAGT

p.Asn589delinsLysAspIleGluAspGlyArgPheLeuSerValSerLeuValLeuVal

p.N589delinsKDIEDGRFLSVSLVLV

Q92630

protein_coding

TCGA-AN-A03X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DYRK2

SNV

Missense_Mutation

novel

c.610N>C

p.Asp204His

p.D204H

Q92630

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A8XH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DYRK2

SNV

Missense_Mutation

rs748801595

c.1447N>T

p.Arg483Trp

p.R483W

Q92630

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DYRK2

SNV

Missense_Mutation

novel

c.1210N>C

p.Asp404His

p.D404H

Q92630

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

DYRK2

SNV

Missense_Mutation

c.563N>T

p.Ala188Val

p.A188V

Q92630

protein_coding

deleterious(0.01)

probably_damaging(0.942)

TCGA-A6-6653-01

Colorectum

colon adenocarcinoma

Male

>=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
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR		PMID28766366-Compound-Scheme21Left
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR	inhibitor	249565847
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR	inhibitor	249565807
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR		PMID28766366-Compound-Scheme16DMAT
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR		HARMINE	HARMINE	22998443
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR		LEUCETTAMINE B	LEUCETTAMINE B	22998443
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR		HARMINE	HARMINE
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR		PMID28766366-Compound-Scheme14BINDY
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR	inhibitor	249565851
8445	DYRK2	SERINE THREONINE KINASE, TYROSINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME, TRANSCRIPTION FACTOR		PMID28766366-Compound-Scheme21Right

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