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: MYLK

Gene summary for MYLK

Gene summary.

Gene information	Species	Human
	Gene symbol	MYLK
	Gene ID	4638
	Gene name	myosin light chain kinase
	Gene Alias	AAT7
	Cytomap	3q21.1
	Gene Type	protein-coding
	GO ID	GO:0001568
	UniProtAcc	Q05B97

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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
4638	MYLK	GSM4909281	Human	Breast	IDC	1.65e-66	1.12e+00	0.21
4638	MYLK	GSM4909282	Human	Breast	IDC	1.27e-22	5.86e-01	-0.0288
4638	MYLK	GSM4909286	Human	Breast	IDC	5.14e-03	4.95e-02	0.1081
4638	MYLK	GSM4909295	Human	Breast	IDC	1.35e-09	5.39e-01	0.0898
4638	MYLK	DCIS2	Human	Breast	DCIS	4.59e-08	-6.81e-02	0.0085
4638	MYLK	HTA11_347_2000001011	Human	Colorectum	AD	7.71e-08	4.77e-01	-0.1954
4638	MYLK	HTA11_411_2000001011	Human	Colorectum	SER	1.25e-02	9.53e-01	-0.2602
4638	MYLK	HTA11_5212_2000001011	Human	Colorectum	AD	1.04e-07	6.71e-01	-0.2061
4638	MYLK	A002-C-010	Human	Colorectum	FAP	2.39e-03	-2.08e-01	0.242
4638	MYLK	A002-C-201	Human	Colorectum	FAP	1.92e-04	-2.22e-01	0.0324
4638	MYLK	A002-C-203	Human	Colorectum	FAP	7.20e-03	-2.03e-01	0.2786
4638	MYLK	A001-C-108	Human	Colorectum	FAP	4.70e-02	-1.82e-01	-0.0272
4638	MYLK	A001-C-104	Human	Colorectum	FAP	2.10e-02	-1.83e-01	0.0184
4638	MYLK	A015-C-104	Human	Colorectum	FAP	9.36e-06	-2.10e-01	-0.1899
4638	MYLK	A001-C-014	Human	Colorectum	FAP	1.68e-03	-2.01e-01	0.0135
4638	MYLK	A002-C-016	Human	Colorectum	FAP	7.35e-04	-2.05e-01	0.0521
4638	MYLK	A001-C-203	Human	Colorectum	FAP	8.91e-04	-1.82e-01	-0.0481
4638	MYLK	A002-C-116	Human	Colorectum	FAP	9.63e-08	-2.00e-01	-0.0452
4638	MYLK	F034	Human	Colorectum	FAP	6.07e-03	-1.66e-01	-0.0665
4638	MYLK	F072B	Human	Colorectum	FAP	2.18e-02	-1.77e-01	0.257

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
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
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:006219714	Breast	IDC	cellular response to chemical stress	55/1434	337/18723	7.07e-08	4.36e-06	55
GO:007121413	Breast	IDC	cellular response to abiotic stimulus	48/1434	331/18723	1.37e-05	3.53e-04	48
GO:010400413	Breast	IDC	cellular response to environmental stimulus	48/1434	331/18723	1.37e-05	3.53e-04	48
GO:004206014	Breast	IDC	wound healing	55/1434	422/18723	7.27e-05	1.45e-03	55
GO:001095913	Breast	IDC	regulation of metal ion transport	52/1434	406/18723	1.76e-04	2.97e-03	52
GO:006053711	Breast	IDC	muscle tissue development	50/1434	403/18723	4.91e-04	6.45e-03	50
GO:007147011	Breast	IDC	cellular response to osmotic stress	10/1434	41/18723	8.38e-04	9.79e-03	10
GO:190303612	Breast	IDC	positive regulation of response to wounding	14/1434	72/18723	9.93e-04	1.11e-02	14
GO:00432703	Breast	IDC	positive regulation of ion transport	36/1434	275/18723	1.11e-03	1.22e-02	36
GO:190303413	Breast	IDC	regulation of response to wounding	24/1434	167/18723	2.07e-03	1.95e-02	24
GO:0051924	Breast	IDC	regulation of calcium ion transport	32/1434	255/18723	3.94e-03	3.22e-02	32
GO:009030312	Breast	IDC	positive regulation of wound healing	11/1434	59/18723	4.70e-03	3.61e-02	11
GO:0051928	Breast	IDC	positive regulation of calcium ion transport	18/1434	122/18723	5.35e-03	3.95e-02	18
GO:00030125	Breast	IDC	muscle system process	50/1434	452/18723	5.52e-03	4.05e-02	50
GO:00075172	Breast	IDC	muscle organ development	38/1434	327/18723	6.63e-03	4.62e-02	38
GO:006219724	Breast	DCIS	cellular response to chemical stress	56/1390	337/18723	9.64e-09	7.38e-07	56
GO:007121423	Breast	DCIS	cellular response to abiotic stimulus	47/1390	331/18723	1.32e-05	3.31e-04	47
GO:010400423	Breast	DCIS	cellular response to environmental stimulus	47/1390	331/18723	1.32e-05	3.31e-04	47
GO:004206024	Breast	DCIS	wound healing	54/1390	422/18723	6.09e-05	1.22e-03	54
GO:006053721	Breast	DCIS	muscle tissue development	50/1390	403/18723	2.39e-04	3.74e-03	50

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0497122	Breast	IDC	Gastric acid secretion	16/867	76/8465	3.80e-03	2.33e-02	1.74e-02	16
hsa0481014	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa045109	Breast	IDC	Focal adhesion	32/867	203/8465	8.60e-03	4.23e-02	3.17e-02	32
hsa0497132	Breast	IDC	Gastric acid secretion	16/867	76/8465	3.80e-03	2.33e-02	1.74e-02	16
hsa0481015	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0451013	Breast	IDC	Focal adhesion	32/867	203/8465	8.60e-03	4.23e-02	3.17e-02	32
hsa0481023	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa0481033	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa04510	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa045101	Colorectum	AD	Focal adhesion	67/2092	203/8465	4.40e-03	2.17e-02	1.38e-02	67
hsa049712	Colorectum	SER	Gastric acid secretion	27/1580	76/8465	3.65e-04	3.27e-03	2.38e-03	27
hsa048102	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa049713	Colorectum	SER	Gastric acid secretion	27/1580	76/8465	3.65e-04	3.27e-03	2.38e-03	27
hsa048103	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa045102	Colorectum	FAP	Focal adhesion	61/1404	203/8465	1.03e-06	2.15e-05	1.31e-05	61
hsa048106	Colorectum	FAP	Regulation of actin cytoskeleton	65/1404	229/8465	4.07e-06	5.91e-05	3.59e-05	65
hsa049716	Colorectum	FAP	Gastric acid secretion	24/1404	76/8465	8.95e-04	5.20e-03	3.16e-03	24
hsa040222	Colorectum	FAP	cGMP-PKG signaling pathway	42/1404	167/8465	2.84e-03	1.27e-02	7.70e-03	42

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
MYLK	BAS	Prostate	Healthy	TPM2,TPM1,MYL9, etc.	2.86e-01
MYLK	MAST	Skin	SCCIS	ACTA2,CALD1,MYH11, etc.	1.36e-01
MYLK	CD8TRM	Skin	SCCIS	ACTA2,CALD1,MYH11, etc.	2.67e-02

∗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

MYLK

SNV

Missense_Mutation

novel

c.363G>C

p.Leu121Phe

p.L121F

Q15746

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

MYLK

SNV

Missense_Mutation

c.82N>A

p.Pro28Thr

p.P28T

Q15746

protein_coding

tolerated_low_confidence(0.06)

benign(0.417)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

MYLK

SNV

Missense_Mutation

c.637A>C

p.Asn213His

p.N213H

Q15746

protein_coding

deleterious(0.03)

probably_damaging(0.914)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MYLK

SNV

Missense_Mutation

rs201754358

c.455N>A

p.Arg152His

p.R152H

Q15746

protein_coding

deleterious(0.02)

possibly_damaging(0.891)

TCGA-A7-A26F-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

MYLK

SNV

Missense_Mutation

c.5410N>G

p.Lys1804Glu

p.K1804E

Q15746

protein_coding

deleterious(0)

possibly_damaging(0.718)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYLK

SNV

Missense_Mutation

c.1273N>A

p.Val425Ile

p.V425I

Q15746

protein_coding

tolerated(0.05)

benign(0.093)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYLK

SNV

Missense_Mutation

c.1540N>T

p.Pro514Ser

p.P514S

Q15746

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AO-A0JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

leuprolide

MYLK

SNV

Missense_Mutation

rs747368032

c.4709N>T

p.Ser1570Leu

p.S1570L

Q15746

protein_coding

tolerated(0.32)

benign(0.117)

TCGA-AR-A1AO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MYLK

SNV

Missense_Mutation

c.2053G>T

p.Val685Leu

p.V685L

Q15746

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-B6-A0RS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYLK

SNV

Missense_Mutation

c.5398G>A

p.Val1800Ile

p.V1800I

Q15746

protein_coding

deleterious(0.01)

possibly_damaging(0.596)

TCGA-B6-A0X1-01

Breast

breast invasive carcinoma

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
4638	MYLK	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	TOZASERTIB	TOZASERTIB	19035792
4638	MYLK	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	activator	135652052
4638	MYLK	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE		ME-3407
4638	MYLK	ENZYME, KINASE, DRUGGABLE GENOME, SERINE THREONINE KINASE	inhibitor	249565832

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