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: MAP3K10

Gene summary for MAP3K10

Gene summary.

Gene information	Species	Human
	Gene symbol	MAP3K10
	Gene ID	4294
	Gene name	mitogen-activated protein kinase kinase kinase 10
	Gene Alias	MEKK10
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q02779

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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
4294	MAP3K10	PTC06	Human	Thyroid	PTC	8.68e-08	1.16e-01	0.2057
4294	MAP3K10	ATC13	Human	Thyroid	ATC	4.37e-34	5.22e-01	0.34
4294	MAP3K10	ATC2	Human	Thyroid	ATC	3.15e-05	3.24e-01	0.34
4294	MAP3K10	ATC5	Human	Thyroid	ATC	1.13e-41	5.54e-01	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0045860111	Thyroid	PTC	positive regulation of protein kinase activity	176/5968	386/18723	8.89e-09	2.17e-07	176
GO:0071900110	Thyroid	PTC	regulation of protein serine/threonine kinase activity	164/5968	359/18723	2.41e-08	5.43e-07	164
GO:004677716	Thyroid	PTC	protein autophosphorylation	110/5968	227/18723	1.25e-07	2.44e-06	110
GO:0033674111	Thyroid	PTC	positive regulation of kinase activity	201/5968	467/18723	1.95e-07	3.54e-06	201
GO:001810518	Thyroid	PTC	peptidyl-serine phosphorylation	143/5968	315/18723	2.94e-07	5.04e-06	143
GO:001820916	Thyroid	PTC	peptidyl-serine modification	151/5968	338/18723	4.61e-07	7.51e-06	151
GO:001821017	Thyroid	PTC	peptidyl-threonine modification	66/5968	125/18723	9.50e-07	1.43e-05	66
GO:001810717	Thyroid	PTC	peptidyl-threonine phosphorylation	62/5968	116/18723	1.16e-06	1.69e-05	62
GO:0031098111	Thyroid	PTC	stress-activated protein kinase signaling cascade	113/5968	247/18723	3.16e-06	4.10e-05	113
GO:007190210	Thyroid	PTC	positive regulation of protein serine/threonine kinase activity	93/5968	200/18723	1.01e-05	1.12e-04	93
GO:0051403111	Thyroid	PTC	stress-activated MAPK cascade	108/5968	239/18723	1.02e-05	1.13e-04	108
GO:005109016	Thyroid	PTC	regulation of DNA-binding transcription factor activity	178/5968	440/18723	7.63e-05	6.54e-04	178
GO:000725419	Thyroid	PTC	JNK cascade	73/5968	167/18723	8.41e-04	5.17e-03	73
GO:0070302110	Thyroid	PTC	regulation of stress-activated protein kinase signaling cascade	83/5968	195/18723	1.04e-03	6.21e-03	83
GO:0032872110	Thyroid	PTC	regulation of stress-activated MAPK cascade	81/5968	192/18723	1.62e-03	8.95e-03	81
GO:00434057	Thyroid	PTC	regulation of MAP kinase activity	75/5968	177/18723	2.04e-03	1.09e-02	75
GO:00434063	Thyroid	PTC	positive regulation of MAP kinase activity	48/5968	112/18723	9.30e-03	3.83e-02	48
GO:007190025	Thyroid	ATC	regulation of protein serine/threonine kinase activity	176/6293	359/18723	8.35e-10	2.17e-08	176
GO:004586026	Thyroid	ATC	positive regulation of protein kinase activity	185/6293	386/18723	3.00e-09	7.02e-08	185
GO:001810519	Thyroid	ATC	peptidyl-serine phosphorylation	153/6293	315/18723	2.28e-08	4.42e-07	153

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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

MAP3K10

SNV

Missense_Mutation

novel

c.1441N>C

p.Glu481Gln

p.E481Q

Q02779

protein_coding

tolerated(1)

benign(0.007)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

MAP3K10

SNV

Missense_Mutation

c.839N>A

p.Phe280Tyr

p.F280Y

Q02779

protein_coding

deleterious(0.02)

possibly_damaging(0.678)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MAP3K10

SNV

Missense_Mutation

novel

c.922N>T

p.Ala308Ser

p.A308S

Q02779

protein_coding

deleterious(0.02)

benign(0.195)

TCGA-AR-A1AW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

MAP3K10

SNV

Missense_Mutation

rs376121895

c.1036N>A

p.Gly346Arg

p.G346R

Q02779

protein_coding

tolerated(0.63)

benign(0.013)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

MAP3K10

SNV

Missense_Mutation

c.1306N>T

p.Arg436Trp

p.R436W

Q02779

protein_coding

deleterious(0.01)

possibly_damaging(0.812)

TCGA-C8-A137-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MAP3K10

SNV

Missense_Mutation

novel

c.2690A>G

p.Asp897Gly

p.D897G

Q02779

protein_coding

deleterious(0.03)

benign(0.011)

TCGA-LL-A7SZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MAP3K10

SNV

Missense_Mutation

rs768143257

c.1621G>A

p.Gly541Ser

p.G541S

Q02779

protein_coding

tolerated(1)

benign(0)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K10

SNV

Missense_Mutation

c.2543N>A

p.Gly848Asp

p.G848D

Q02779

protein_coding

deleterious(0.04)

benign(0.04)

TCGA-EK-A2RC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K10

SNV

Missense_Mutation

novel

c.604C>G

p.Gln202Glu

p.Q202E

Q02779

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MAP3K10

SNV

Missense_Mutation

novel

c.1409N>A

p.Gly470Asp

p.G470D

Q02779

protein_coding

tolerated(0.43)

benign(0.003)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

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
4294	MAP3K10	SERINE THREONINE KINASE, ENZYME, KINASE, DRUGGABLE GENOME		DOVITINIB	DOVITINIB
4294	MAP3K10	SERINE THREONINE KINASE, ENZYME, KINASE, DRUGGABLE GENOME	inhibitor	249565786
4294	MAP3K10	SERINE THREONINE KINASE, ENZYME, KINASE, DRUGGABLE GENOME		PF-562271	PF-00562271
4294	MAP3K10	SERINE THREONINE KINASE, ENZYME, KINASE, DRUGGABLE GENOME		DASATINIB	DASATINIB
4294	MAP3K10	SERINE THREONINE KINASE, ENZYME, KINASE, DRUGGABLE GENOME	inhibitor	249565853	CEP-1347
4294	MAP3K10	SERINE THREONINE KINASE, ENZYME, KINASE, DRUGGABLE GENOME		TOZASERTIB	TOZASERTIB
4294	MAP3K10	SERINE THREONINE KINASE, ENZYME, KINASE, DRUGGABLE GENOME		TAMATINIB	R-406
4294	MAP3K10	SERINE THREONINE KINASE, ENZYME, KINASE, DRUGGABLE GENOME	inhibitor	CHEMBL290352	CEP-1347

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