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: MAPK10

Gene summary for MAPK10

Gene summary.

Gene information	Species	Human
	Gene symbol	MAPK10
	Gene ID	5602
	Gene name	mitogen-activated protein kinase 10
	Gene Alias	JNK3
	Cytomap	4q21.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A286YF97

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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
5602	MAPK10	CCI_1	Human	Cervix	CC	1.40e-30	2.46e+00	0.528
5602	MAPK10	CCI_3	Human	Cervix	CC	6.47e-03	1.04e+00	0.516
5602	MAPK10	TD9	Human	Lung	IAC	5.75e-06	9.27e-01	0.088
5602	MAPK10	RNA-P10T2-P10T2-1	Human	Lung	AAH	3.29e-04	9.52e-01	-0.1271
5602	MAPK10	RNA-P10T2-P10T2-2	Human	Lung	AAH	9.24e-10	1.25e+00	-0.1406
5602	MAPK10	RNA-P10T2-P10T2-3	Human	Lung	AAH	5.89e-05	9.65e-01	-0.1408
5602	MAPK10	RNA-P10T2-P10T2-4	Human	Lung	AAH	2.47e-10	1.26e+00	-0.138
5602	MAPK10	RNA-P17T-P17T-8	Human	Lung	IAC	1.46e-03	5.38e-01	0.3329
5602	MAPK10	RNA-P18T-P18T-2	Human	Lung	IAC	2.18e-02	1.21e+00	0.1129
5602	MAPK10	RNA-P18T-P18T-4	Human	Lung	IAC	1.20e-05	1.51e+00	0.1024
5602	MAPK10	RNA-P18T-P18T-8	Human	Lung	IAC	1.77e-04	1.55e+00	0.1151
5602	MAPK10	RNA-P25T1-P25T1-1	Human	Lung	AIS	2.23e-25	1.17e+00	-0.2116
5602	MAPK10	RNA-P25T1-P25T1-2	Human	Lung	AIS	4.30e-12	1.15e+00	-0.1941
5602	MAPK10	RNA-P25T1-P25T1-3	Human	Lung	AIS	2.42e-15	1.09e+00	-0.2107
5602	MAPK10	RNA-P25T1-P25T1-4	Human	Lung	AIS	1.26e-23	1.16e+00	-0.2119
5602	MAPK10	RNA-P6T1-P6T1-1	Human	Lung	MIAC	9.11e-08	1.33e+00	-0.0238
5602	MAPK10	RNA-P6T1-P6T1-2	Human	Lung	MIAC	2.11e-07	1.26e+00	-0.0186
5602	MAPK10	RNA-P6T1-P6T1-3	Human	Lung	MIAC	4.76e-06	1.27e+00	-0.0296
5602	MAPK10	RNA-P6T1-P6T1-4	Human	Lung	MIAC	2.06e-13	1.42e+00	-0.0263
5602	MAPK10	RNA-P6T2-P6T2-1	Human	Lung	IAC	1.77e-63	1.54e+00	-0.0166

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
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:19907788	Cervix	CC	protein localization to cell periphery	78/2311	333/18723	1.22e-08	9.73e-07	78
GO:006219710	Cervix	CC	cellular response to chemical stress	76/2311	337/18723	1.01e-07	5.25e-06	76
GO:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:00075689	Cervix	CC	aging	75/2311	339/18723	2.75e-07	1.13e-05	75
GO:00310988	Cervix	CC	stress-activated protein kinase signaling cascade	58/2311	247/18723	8.02e-07	2.89e-05	58
GO:00485118	Cervix	CC	rhythmic process	65/2311	298/18723	2.79e-06	8.04e-05	65
GO:00514038	Cervix	CC	stress-activated MAPK cascade	55/2311	239/18723	2.96e-06	8.31e-05	55
GO:00380933	Cervix	CC	Fc receptor signaling pathway	19/2311	50/18723	3.42e-06	9.17e-05	19
GO:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:00712148	Cervix	CC	cellular response to abiotic stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:01040048	Cervix	CC	cellular response to environmental stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:00075695	Cervix	CC	cell aging	34/2311	132/18723	1.92e-05	3.53e-04	34
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:00988767	Cervix	CC	vesicle-mediated transport to the plasma membrane	34/2311	136/18723	3.75e-05	5.91e-04	34
GO:0038095	Cervix	CC	Fc-epsilon receptor signaling pathway	11/2311	24/18723	5.28e-05	7.88e-04	11
GO:00076238	Cervix	CC	circadian rhythm	46/2311	210/18723	6.76e-05	9.60e-04	46
GO:00901509	Cervix	CC	establishment of protein localization to membrane	54/2311	260/18723	7.67e-05	1.05e-03	54
GO:00903981	Cervix	CC	cellular senescence	25/2311	93/18723	1.11e-04	1.40e-03	25
GO:00011016	Cervix	CC	response to acid chemical	31/2311	135/18723	4.16e-04	4.22e-03	31
GO:0002768	Cervix	CC	immune response-regulating cell surface receptor signaling pathway	59/2311	315/18723	6.64e-04	6.11e-03	59

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0401021	Lung	AIS	MAPK signaling pathway	57/961	302/8465	6.41e-05	9.43e-04	6.03e-04	57
hsa0516623	Lung	AIS	Human T-cell leukemia virus 1 infection	45/961	222/8465	6.69e-05	9.43e-04	6.03e-04	45
hsa0516722	Lung	AIS	Kaposi sarcoma-associated herpesvirus infection	40/961	194/8465	1.14e-04	1.42e-03	9.10e-04	40
hsa0513523	Lung	AIS	Yersinia infection	30/961	137/8465	2.70e-04	2.92e-03	1.87e-03	30
hsa0401221	Lung	AIS	ErbB signaling pathway	21/961	85/8465	4.06e-04	3.87e-03	2.47e-03	21
hsa0523121	Lung	AIS	Choline metabolism in cancer	23/961	98/8465	4.87e-04	4.39e-03	2.81e-03	23
hsa0414123	Lung	AIS	Protein processing in endoplasmic reticulum	35/961	174/8465	4.88e-04	4.39e-03	2.81e-03	35
hsa046592	Lung	AIS	Th17 cell differentiation	24/961	108/8465	8.59e-04	7.11e-03	4.55e-03	24
hsa0413722	Lung	AIS	Mitophagy - animal	18/961	72/8465	8.86e-04	7.11e-03	4.55e-03	18
hsa015222	Lung	AIS	Endocrine resistance	22/961	98/8465	1.21e-03	9.02e-03	5.77e-03	22
hsa0521023	Lung	AIS	Colorectal cancer	20/961	86/8465	1.25e-03	9.02e-03	5.77e-03	20
hsa0472221	Lung	AIS	Neurotrophin signaling pathway	25/961	119/8465	1.59e-03	1.05e-02	6.72e-03	25
hsa0407121	Lung	AIS	Sphingolipid signaling pathway	25/961	121/8465	2.03e-03	1.29e-02	8.24e-03	25
hsa046252	Lung	AIS	C-type lectin receptor signaling pathway	22/961	104/8465	2.70e-03	1.59e-02	1.02e-02	22
hsa0491221	Lung	AIS	GnRH signaling pathway	20/961	93/8465	3.38e-03	1.89e-02	1.21e-02	20
hsa0492621	Lung	AIS	Relaxin signaling pathway	25/961	129/8465	4.95e-03	2.47e-02	1.58e-02	25
hsa0406821	Lung	AIS	FoxO signaling pathway	25/961	131/8465	6.07e-03	2.94e-02	1.88e-02	25
hsa0501223	Lung	AIS	Parkinson disease	44/961	266/8465	6.25e-03	2.98e-02	1.91e-02	44
hsa0493521	Lung	AIS	Growth hormone synthesis, secretion and action	23/961	120/8465	7.85e-03	3.58e-02	2.29e-02	23
hsa0414022	Lung	AIS	Autophagy - animal	26/961	141/8465	8.23e-03	3.71e-02	2.37e-02	26

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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

MAPK10

SNV

Missense_Mutation

c.545N>G

p.Ser182Cys

p.S182C

P53779

protein_coding

deleterious(0)

probably_damaging(0.93)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAPK10

SNV

Missense_Mutation

c.644N>A

p.Gly215Asp

p.G215D

P53779

protein_coding

tolerated(0.64)

benign(0.013)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAPK10

SNV

Missense_Mutation

rs143720396

c.242N>T

p.Ala81Val

p.A81V

P53779

protein_coding

deleterious(0.01)

probably_damaging(0.954)

TCGA-AR-A1AI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MAPK10

SNV

Missense_Mutation

c.712N>T

p.Met238Leu

p.M238L

P53779

protein_coding

tolerated(0.1)

benign(0.03)

TCGA-AR-A24Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MAPK10

SNV

Missense_Mutation

c.328C>G

p.Arg110Gly

p.R110G

P53779

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-GM-A2DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

MAPK10

insertion

In_Frame_Ins

novel

c.1309_1310insTTGATGATAAGAATCTCTCTCTGGAACTGAGCAGAATTG

p.Ser437delinsPheAspAspLysAsnLeuSerLeuGluLeuSerArgIleAla

p.S437delinsFDDKNLSLELSRIA

P53779

protein_coding

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MAPK10

insertion

In_Frame_Ins

novel

c.1113_1114insAAAGCTTGCCCC

p.Pro371_Pro372insLysAlaCysPro

p.P371_P372insKACP

P53779

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAPK10

SNV

Missense_Mutation

novel

c.1120N>G

p.Gln374Glu

p.Q374E

P53779

protein_coding

tolerated(0.61)

benign(0.001)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

MAPK10

SNV

Missense_Mutation

rs752620406

c.680N>A

p.Arg227His

p.R227H

P53779

protein_coding

deleterious(0.01)

possibly_damaging(0.466)

TCGA-A6-5661-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MAPK10

SNV

Missense_Mutation

rs757125320

c.959C>T

p.Ala320Val

p.A320V

P53779

protein_coding

tolerated(0.2)

benign(0.041)

TCGA-AA-3713-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

5-fluorouracil

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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
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		DORAMAPIMOD	DORAMAPIMOD
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		PMID25991433-Compound-P6
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		AM-111	BRIMAPITIDE, C-TERMINAL ACID
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		PMID25991433-Compound-P4
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		BLEOMYCIN A5		14675139
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	178102620
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		SB-202190	SB-202190	22951114
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		AG-1879	CHEMBL406845
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		ARSENIC TRIOXIDE		17332940
5602	MAPK10	KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME, SERINE THREONINE KINASE		AST-487	AST-487

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