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: DYRK3

Gene summary for DYRK3

Gene summary.

Gene information	Species	Human
	Gene symbol	DYRK3
	Gene ID	8444
	Gene name	dual specificity tyrosine phosphorylation regulated kinase 3
	Gene Alias	DYRK5
	Cytomap	1q32.1
	Gene Type	protein-coding
	GO ID	GO:0002262
	UniProtAcc	O43781

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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
8444	DYRK3	LZE24T	Human	Esophagus	ESCC	6.07e-08	9.36e-02	0.0596
8444	DYRK3	P2T-E	Human	Esophagus	ESCC	7.97e-16	3.64e-01	0.1177
8444	DYRK3	P5T-E	Human	Esophagus	ESCC	2.01e-06	4.90e-02	0.1327
8444	DYRK3	P8T-E	Human	Esophagus	ESCC	4.57e-15	1.27e-02	0.0889
8444	DYRK3	P10T-E	Human	Esophagus	ESCC	2.68e-07	6.06e-03	0.116
8444	DYRK3	P11T-E	Human	Esophagus	ESCC	1.36e-04	3.81e-01	0.1426
8444	DYRK3	P15T-E	Human	Esophagus	ESCC	1.12e-02	3.27e-02	0.1149
8444	DYRK3	P16T-E	Human	Esophagus	ESCC	3.33e-11	4.14e-02	0.1153
8444	DYRK3	P20T-E	Human	Esophagus	ESCC	7.11e-13	3.06e-01	0.1124
8444	DYRK3	P21T-E	Human	Esophagus	ESCC	9.06e-16	2.24e-01	0.1617
8444	DYRK3	P22T-E	Human	Esophagus	ESCC	8.90e-12	1.73e-01	0.1236
8444	DYRK3	P23T-E	Human	Esophagus	ESCC	5.29e-04	1.16e-01	0.108
8444	DYRK3	P24T-E	Human	Esophagus	ESCC	2.22e-04	1.45e-01	0.1287
8444	DYRK3	P26T-E	Human	Esophagus	ESCC	3.77e-04	6.92e-02	0.1276
8444	DYRK3	P27T-E	Human	Esophagus	ESCC	2.26e-06	9.18e-02	0.1055
8444	DYRK3	P28T-E	Human	Esophagus	ESCC	5.80e-07	5.17e-02	0.1149
8444	DYRK3	P30T-E	Human	Esophagus	ESCC	1.17e-05	3.42e-01	0.137
8444	DYRK3	P31T-E	Human	Esophagus	ESCC	2.76e-06	9.75e-02	0.1251
8444	DYRK3	P32T-E	Human	Esophagus	ESCC	3.75e-05	1.63e-01	0.1666
8444	DYRK3	P36T-E	Human	Esophagus	ESCC	2.97e-14	5.70e-01	0.1187

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias

∗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:0022411111	Esophagus	ESCC	cellular component disassembly	305/8552	443/18723	1.94e-23	4.57e-21	305
GO:0071826111	Esophagus	ESCC	ribonucleoprotein complex subunit organization	166/8552	227/18723	2.94e-17	2.42e-15	166
GO:0072331111	Esophagus	ESCC	signal transduction by p53 class mediator	121/8552	163/18723	9.61e-14	4.69e-12	121
GO:190300816	Esophagus	ESCC	organelle disassembly	89/8552	114/18723	1.36e-12	5.80e-11	89
GO:003298416	Esophagus	ESCC	protein-containing complex disassembly	151/8552	224/18723	3.45e-11	1.15e-09	151
GO:190198713	Esophagus	ESCC	regulation of cell cycle phase transition	242/8552	390/18723	3.86e-11	1.26e-09	242
GO:000699713	Esophagus	ESCC	nucleus organization	96/8552	133/18723	4.66e-10	1.21e-08	96
GO:2001020110	Esophagus	ESCC	regulation of response to DNA damage stimulus	145/8552	219/18723	5.97e-10	1.50e-08	145
GO:004578710	Esophagus	ESCC	positive regulation of cell cycle	196/8552	313/18723	9.27e-10	2.24e-08	196
GO:0030099111	Esophagus	ESCC	myeloid cell differentiation	232/8552	381/18723	1.22e-09	2.90e-08	232
GO:004277014	Esophagus	ESCC	signal transduction in response to DNA damage	117/8552	172/18723	2.38e-09	5.32e-08	117
GO:00448394	Esophagus	ESCC	cell cycle G2/M phase transition	103/8552	148/18723	3.09e-09	6.67e-08	103
GO:1901796111	Esophagus	ESCC	regulation of signal transduction by p53 class mediator	70/8552	93/18723	5.69e-09	1.18e-07	70
GO:0002262111	Esophagus	ESCC	myeloid cell homeostasis	104/8552	157/18723	1.49e-07	2.36e-06	104
GO:0034101111	Esophagus	ESCC	erythrocyte homeostasis	88/8552	129/18723	1.81e-07	2.84e-06	88
GO:0030330110	Esophagus	ESCC	DNA damage response, signal transduction by p53 class mediator	53/8552	72/18723	1.34e-06	1.63e-05	53
GO:0048872111	Esophagus	ESCC	homeostasis of number of cells	163/8552	272/18723	1.40e-06	1.69e-05	163
GO:0030218111	Esophagus	ESCC	erythrocyte differentiation	80/8552	120/18723	2.69e-06	3.08e-05	80
GO:00182099	Esophagus	ESCC	peptidyl-serine modification	196/8552	338/18723	3.07e-06	3.47e-05	196
GO:19019896	Esophagus	ESCC	positive regulation of cell cycle phase transition	77/8552	115/18723	3.20e-06	3.58e-05	77

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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

DYRK3

SNV

Missense_Mutation

rs782184680

c.842N>A

p.Arg281Gln

p.R281Q

O43781

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DYRK3

SNV

Missense_Mutation

rs782784518

c.1109N>C

p.Ile370Thr

p.I370T

O43781

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DYRK3

SNV

Missense_Mutation

c.317N>T

p.Ser106Ile

p.S106I

O43781

protein_coding

tolerated(0.05)

benign(0.013)

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

DYRK3

SNV

Missense_Mutation

novel

c.1205T>G

p.Leu402Arg

p.L402R

O43781

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-E2-A56Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DYRK3

insertion

Frame_Shift_Ins

novel

c.1556_1557insAATGGTGCGCAATGAGAAG

p.His519GlnfsTer11

p.H519Qfs*11

O43781

protein_coding

TCGA-AN-A0FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DYRK3

deletion

Frame_Shift_Del

novel

c.990delG

p.Ile331LeufsTer6

p.I331Lfs*6

O43781

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

DYRK3

SNV

Missense_Mutation

novel

c.244N>A

p.Glu82Lys

p.E82K

O43781

protein_coding

tolerated_low_confidence(0.1)

benign(0.013)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

DYRK3

SNV

Missense_Mutation

c.1003G>A

p.Asp335Asn

p.D335N

O43781

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3510-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

DYRK3

SNV

Missense_Mutation

novel

c.1259N>A

p.Cys420Tyr

p.C420Y

O43781

protein_coding

deleterious(0)

probably_damaging(0.959)

TCGA-AA-3877-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

DYRK3

SNV

Missense_Mutation

rs782306516

c.1084G>A

p.Glu362Lys

p.E362K

O43781

protein_coding

deleterious(0)

probably_damaging(0.955)

TCGA-AA-A00N-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
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		SORAFENIB	SORAFENIB
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	249565807
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		PHA-767491	CHEMBL225519
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		LINIFANIB	LINIFANIB
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		BAY-613606	CHEMBL541400
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		HARMINE	HARMINE
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		SNS-314	SNS-314
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		DASATINIB	DASATINIB
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME		AZD-1080	AZD-1080
8444	DYRK3	TYROSINE KINASE, SERINE THREONINE KINASE, KINASE, DRUGGABLE GENOME, ENZYME	inhibitor	384403651

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