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: MYO6

Gene summary for MYO6

Gene summary.

Gene information	Species	Human
	Gene symbol	MYO6
	Gene ID	4646
	Gene name	myosin VI
	Gene Alias	DFNA22
	Cytomap	6q14.1
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	Q9UM54

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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
4646	MYO6	CA_HPV_1	Human	Cervix	CC	3.23e-05	-2.37e-01	0.0264
4646	MYO6	CCI_3	Human	Cervix	CC	1.01e-07	7.43e-01	0.516
4646	MYO6	H2	Human	Cervix	HSIL_HPV	2.37e-32	7.81e-01	0.0632
4646	MYO6	HTA11_3410_2000001011	Human	Colorectum	AD	2.69e-12	-5.77e-01	0.0155
4646	MYO6	HTA11_696_2000001011	Human	Colorectum	AD	2.52e-02	-2.89e-01	-0.1464
4646	MYO6	HTA11_866_3004761011	Human	Colorectum	AD	7.19e-11	-5.89e-01	0.096
4646	MYO6	HTA11_8622_2000001021	Human	Colorectum	SER	3.88e-02	-5.35e-01	0.0528
4646	MYO6	HTA11_10711_2000001011	Human	Colorectum	AD	1.81e-03	-4.74e-01	0.0338
4646	MYO6	HTA11_7696_3000711011	Human	Colorectum	AD	9.31e-09	-3.87e-01	0.0674
4646	MYO6	HTA11_6818_2000001021	Human	Colorectum	AD	1.89e-02	-5.00e-01	0.0588
4646	MYO6	HTA11_99999965104_69814	Human	Colorectum	MSS	7.86e-03	4.85e-01	0.281
4646	MYO6	HTA11_99999974143_84620	Human	Colorectum	MSS	3.73e-08	-4.53e-01	0.3005
4646	MYO6	F007	Human	Colorectum	FAP	2.11e-02	4.28e-02	0.1176
4646	MYO6	A001-C-207	Human	Colorectum	FAP	2.01e-02	3.40e-02	0.1278
4646	MYO6	A015-C-203	Human	Colorectum	FAP	2.65e-33	-2.69e-01	-0.1294
4646	MYO6	A015-C-204	Human	Colorectum	FAP	7.85e-06	-1.66e-01	-0.0228
4646	MYO6	A014-C-040	Human	Colorectum	FAP	1.14e-03	-1.73e-01	-0.1184
4646	MYO6	A002-C-201	Human	Colorectum	FAP	9.96e-12	-4.21e-02	0.0324
4646	MYO6	A002-C-203	Human	Colorectum	FAP	3.16e-06	1.80e-01	0.2786
4646	MYO6	A001-C-119	Human	Colorectum	FAP	3.50e-10	2.44e-01	-0.1557

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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
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:00085446	Cervix	CC	epidermis development	83/2311	324/18723	3.91e-11	8.54e-09	83
GO:00099137	Cervix	CC	epidermal cell differentiation	53/2311	202/18723	5.48e-08	3.25e-06	53
GO:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:007233110	Cervix	CC	signal transduction by p53 class mediator	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:00300487	Cervix	CC	actin filament-based movement	29/2311	127/18723	6.91e-04	6.33e-03	29
GO:00307057	Cervix	CC	cytoskeleton-dependent intracellular transport	40/2311	195/18723	7.92e-04	6.99e-03	40
GO:00094109	Cervix	CC	response to xenobiotic stimulus	78/2311	462/18723	2.39e-03	1.70e-02	78
GO:00995157	Cervix	CC	actin filament-based transport	8/2311	21/18723	2.44e-03	1.71e-02	8
GO:00427705	Cervix	CC	signal transduction in response to DNA damage	34/2311	172/18723	3.52e-03	2.27e-02	34
GO:00300507	Cervix	CC	vesicle transport along actin filament	7/2311	19/18723	5.65e-03	3.25e-02	7
GO:000854413	Cervix	HSIL_HPV	epidermis development	38/737	324/18723	1.92e-09	3.23e-07	38
GO:000701515	Cervix	HSIL_HPV	actin filament organization	43/737	442/18723	4.77e-08	3.59e-06	43
GO:000991313	Cervix	HSIL_HPV	epidermal cell differentiation	26/737	202/18723	1.10e-07	7.15e-06	26
GO:007233115	Cervix	HSIL_HPV	signal transduction by p53 class mediator	21/737	163/18723	1.78e-06	7.60e-05	21
GO:003004813	Cervix	HSIL_HPV	actin filament-based movement	12/737	127/18723	4.37e-03	3.68e-02	12
GO:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0072331	Colorectum	AD	signal transduction by p53 class mediator	58/3918	163/18723	1.04e-05	2.40e-04	58
GO:0051650	Colorectum	AD	establishment of vesicle localization	57/3918	161/18723	1.47e-05	3.15e-04	57

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513020	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0513220	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa05132110	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa0513225	Cervix	HSIL_HPV	Salmonella infection	34/459	249/8465	5.03e-07	1.13e-05	9.17e-06	34
hsa0513025	Cervix	HSIL_HPV	Pathogenic Escherichia coli infection	28/459	197/8465	2.36e-06	4.61e-05	3.73e-05	28
hsa0513235	Cervix	HSIL_HPV	Salmonella infection	34/459	249/8465	5.03e-07	1.13e-05	9.17e-06	34
hsa0513035	Cervix	HSIL_HPV	Pathogenic Escherichia coli infection	28/459	197/8465	2.36e-06	4.61e-05	3.73e-05	28
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051321	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051322	Colorectum	SER	Salmonella infection	77/1580	249/8465	1.56e-06	2.35e-05	1.71e-05	77
hsa051323	Colorectum	SER	Salmonella infection	77/1580	249/8465	1.56e-06	2.35e-05	1.71e-05	77
hsa051324	Colorectum	MSS	Salmonella infection	92/1875	249/8465	5.23e-08	9.74e-07	5.97e-07	92
hsa051304	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa051325	Colorectum	MSS	Salmonella infection	92/1875	249/8465	5.23e-08	9.74e-07	5.97e-07	92
hsa051305	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa051308	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62
hsa051328	Colorectum	FAP	Salmonella infection	67/1404	249/8465	2.04e-05	2.52e-04	1.53e-04	67

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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

MYO6

SNV

Missense_Mutation

rs199798449

c.1030N>A

p.Val344Ile

p.V344I

Q9UM54

protein_coding

tolerated(0.14)

possibly_damaging(0.787)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

MYO6

SNV

Missense_Mutation

c.196N>T

p.Met66Leu

p.M66L

Q9UM54

protein_coding

deleterious(0.02)

possibly_damaging(0.527)

TCGA-A2-A1G4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

MYO6

SNV

Missense_Mutation

rs753343273

c.2687N>G

p.Gln896Arg

p.Q896R

Q9UM54

protein_coding

deleterious(0.04)

benign(0.025)

TCGA-A7-A6VV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

MYO6

SNV

Missense_Mutation

c.1720N>C

p.Asp574His

p.D574H

Q9UM54

protein_coding

deleterious(0.02)

probably_damaging(0.999)

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYO6

SNV

Missense_Mutation

c.1753N>C

p.Ala585Pro

p.A585P

Q9UM54

protein_coding

deleterious(0.04)

probably_damaging(0.993)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYO6

SNV

Missense_Mutation

novel

c.3487N>A

p.Glu1163Lys

p.E1163K

Q9UM54

protein_coding

tolerated(0.86)

possibly_damaging(0.832)

TCGA-E2-A1IH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

aromasin

MYO6

SNV

Missense_Mutation

c.376C>T

p.His126Tyr

p.H126Y

Q9UM54

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-EW-A1J6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

MYO6

SNV

Missense_Mutation

c.2531N>A

p.Gly844Asp

p.G844D

Q9UM54

protein_coding

tolerated(0.36)

benign(0.015)

TCGA-GM-A2DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

MYO6

SNV

Missense_Mutation

c.1343N>T

p.Ser448Leu

p.S448L

Q9UM54

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MYO6

SNV

Missense_Mutation

novel

c.3664N>T

p.Asp1222Tyr

p.D1222Y

Q9UM54

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-LD-A74U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

taxotere

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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

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