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: MINK1

Gene summary for MINK1

Gene summary.

Gene information	Species	Human
	Gene symbol	MINK1
	Gene ID	50488
	Gene name	misshapen like kinase 1
	Gene Alias	B55
	Cytomap	17p13.2
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q8N4C8

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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
50488	MINK1	CCI_1	Human	Cervix	CC	5.77e-04	6.71e-01	0.528
50488	MINK1	CCI_2	Human	Cervix	CC	1.21e-05	8.78e-01	0.5249
50488	MINK1	LZE4T	Human	Esophagus	ESCC	8.57e-10	2.45e-01	0.0811
50488	MINK1	LZE5T	Human	Esophagus	ESCC	5.76e-03	1.63e-01	0.0514
50488	MINK1	LZE7T	Human	Esophagus	ESCC	3.11e-14	3.74e-01	0.0667
50488	MINK1	LZE8T	Human	Esophagus	ESCC	1.23e-09	2.50e-01	0.067
50488	MINK1	LZE20T	Human	Esophagus	ESCC	4.39e-05	1.44e-01	0.0662
50488	MINK1	LZE22D1	Human	Esophagus	HGIN	2.36e-05	1.02e-01	0.0595
50488	MINK1	LZE22T	Human	Esophagus	ESCC	5.60e-06	3.48e-01	0.068
50488	MINK1	LZE24T	Human	Esophagus	ESCC	1.37e-18	5.57e-01	0.0596
50488	MINK1	LZE21T	Human	Esophagus	ESCC	1.24e-04	2.05e-01	0.0655
50488	MINK1	P1T-E	Human	Esophagus	ESCC	1.18e-16	5.66e-01	0.0875
50488	MINK1	P2T-E	Human	Esophagus	ESCC	8.96e-16	1.47e-01	0.1177
50488	MINK1	P4T-E	Human	Esophagus	ESCC	1.83e-07	7.92e-02	0.1323
50488	MINK1	P5T-E	Human	Esophagus	ESCC	2.39e-18	6.74e-02	0.1327
50488	MINK1	P8T-E	Human	Esophagus	ESCC	1.14e-25	4.31e-01	0.0889
50488	MINK1	P9T-E	Human	Esophagus	ESCC	1.58e-20	2.03e-01	0.1131
50488	MINK1	P10T-E	Human	Esophagus	ESCC	1.55e-13	1.38e-01	0.116
50488	MINK1	P11T-E	Human	Esophagus	ESCC	2.85e-08	3.48e-01	0.1426
50488	MINK1	P12T-E	Human	Esophagus	ESCC	1.17e-13	2.10e-01	0.1122

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:001081010	Cervix	CC	regulation of cell-substrate adhesion	69/2311	221/18723	8.57e-14	5.69e-11	69
GO:00315898	Cervix	CC	cell-substrate adhesion	96/2311	363/18723	1.48e-13	8.85e-11	96
GO:002240710	Cervix	CC	regulation of cell-cell adhesion	103/2311	448/18723	1.78e-10	2.87e-08	103
GO:00019528	Cervix	CC	regulation of cell-matrix adhesion	40/2311	128/18723	1.32e-08	1.04e-06	40
GO:00071608	Cervix	CC	cell-matrix adhesion	60/2311	233/18723	1.58e-08	1.23e-06	60
GO:00163587	Cervix	CC	dendrite development	58/2311	243/18723	4.52e-07	1.76e-05	58
GO:00310988	Cervix	CC	stress-activated protein kinase signaling cascade	58/2311	247/18723	8.02e-07	2.89e-05	58
GO:00514038	Cervix	CC	stress-activated MAPK cascade	55/2311	239/18723	2.96e-06	8.31e-05	55
GO:00315328	Cervix	CC	actin cytoskeleton reorganization	31/2311	107/18723	3.34e-06	8.99e-05	31
GO:00703027	Cervix	CC	regulation of stress-activated protein kinase signaling cascade	46/2311	195/18723	9.35e-06	2.11e-04	46
GO:00434104	Cervix	CC	positive regulation of MAPK cascade	90/2311	480/18723	2.92e-05	4.83e-04	90
GO:00328727	Cervix	CC	regulation of stress-activated MAPK cascade	44/2311	192/18723	3.09e-05	5.10e-04	44
GO:00380664	Cervix	CC	p38MAPK cascade	17/2311	55/18723	2.25e-04	2.54e-03	17
GO:00072545	Cervix	CC	JNK cascade	35/2311	167/18723	1.10e-03	9.09e-03	35
GO:19007442	Cervix	CC	regulation of p38MAPK cascade	14/2311	47/18723	1.18e-03	9.56e-03	14
GO:00463285	Cervix	CC	regulation of JNK cascade	28/2311	133/18723	3.06e-03	2.01e-02	28
GO:00488135	Cervix	CC	dendrite morphogenesis	30/2311	146/18723	3.27e-03	2.13e-02	30
GO:00703043	Cervix	CC	positive regulation of stress-activated protein kinase signaling cascade	27/2311	128/18723	3.49e-03	2.26e-02	27
GO:003158919	Esophagus	ESCC	cell-substrate adhesion	221/8552	363/18723	3.06e-09	6.62e-08	221
GO:001081020	Esophagus	ESCC	regulation of cell-substrate adhesion	144/8552	221/18723	3.55e-09	7.45e-08	144

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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

MINK1

SNV

Missense_Mutation

c.187N>A

p.Glu63Lys

p.E63K

Q8N4C8

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MINK1

SNV

Missense_Mutation

c.3134N>A

p.Arg1045Gln

p.R1045Q

Q8N4C8

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MINK1

SNV

Missense_Mutation

c.566T>A

p.Ile189Asn

p.I189N

Q8N4C8

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-AO-A12H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MINK1

SNV

Missense_Mutation

rs773979222

c.2266N>A

p.Gly756Arg

p.G756R

Q8N4C8

protein_coding

tolerated(0.24)

possibly_damaging(0.573)

TCGA-BH-A0DQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MINK1

deletion

Frame_Shift_Del

novel

c.196delN

p.Ile66SerfsTer8

p.I66Sfs*8

Q8N4C8

protein_coding

TCGA-A2-A0T2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

MINK1

insertion

Frame_Shift_Ins

novel

c.2784_2785insT

p.Pro929SerfsTer8

p.P929Sfs*8

Q8N4C8

protein_coding

TCGA-A7-A6VV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

MINK1

insertion

Frame_Shift_Ins

novel

c.3050_3051insGGATCTACCAGCCTGGAGGCAGTGGGGACAGCATCCCC

p.Phe1018AspfsTer36

p.F1018Dfs*36

Q8N4C8

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

MINK1

deletion

Frame_Shift_Del

novel

c.416delN

p.Gly140ValfsTer10

p.G140Vfs*10

Q8N4C8

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MINK1

SNV

Missense_Mutation

novel

c.263N>T

p.Ala88Val

p.A88V

Q8N4C8

protein_coding

deleterious(0.02)

probably_damaging(0.982)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MINK1

SNV

Missense_Mutation

rs747562269

c.896N>A

p.Arg299His

p.R299H

Q8N4C8

protein_coding

deleterious(0.05)

probably_damaging(0.96)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		BAY-613606	CHEMBL541400
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		PD-0166285	PD-0166285
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		SB-242235	SB-242235
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		ILORASERTIB	ILORASERTIB
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		ERLOTINIB	ERLOTINIB
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		CEDIRANIB	CEDIRANIB
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		PF-562271	PF-00562271
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		DOVITINIB	DOVITINIB
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		SNS-314	SNS-314
50488	MINK1	DRUGGABLE GENOME, KINASE, ENZYME, SERINE THREONINE KINASE		TOZASERTIB	TOZASERTIB

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