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: MYH14

Gene summary for MYH14

Gene summary.

Gene information	Species	Human
	Gene symbol	MYH14
	Gene ID	79784
	Gene name	myosin heavy chain 14
	Gene Alias	DFNA4
	Cytomap	19q13.33
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	B3KWH4

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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
79784	MYH14	CA_HPV_2	Human	Cervix	CC	1.62e-08	4.30e-01	0.0391
79784	MYH14	CCI_1	Human	Cervix	CC	3.71e-12	1.15e+00	0.528
79784	MYH14	CCI_3	Human	Cervix	CC	3.86e-13	9.59e-01	0.516
79784	MYH14	CCII_1	Human	Cervix	CC	2.40e-02	2.94e-01	0.3249
79784	MYH14	Tumor	Human	Cervix	CC	6.27e-11	3.81e-01	0.1241
79784	MYH14	sample3	Human	Cervix	CC	3.17e-21	4.46e-01	0.1387
79784	MYH14	H2	Human	Cervix	HSIL_HPV	2.27e-08	3.52e-01	0.0632
79784	MYH14	T3	Human	Cervix	CC	2.35e-19	4.77e-01	0.1389
79784	MYH14	HTA11_2487_2000001011	Human	Colorectum	SER	6.91e-09	8.24e-01	-0.1808
79784	MYH14	HTA11_1938_2000001011	Human	Colorectum	AD	2.93e-02	4.30e-01	-0.0811
79784	MYH14	HTA11_347_2000001011	Human	Colorectum	AD	2.63e-15	8.92e-01	-0.1954
79784	MYH14	HTA11_411_2000001011	Human	Colorectum	SER	1.90e-07	1.36e+00	-0.2602
79784	MYH14	HTA11_2112_2000001011	Human	Colorectum	SER	7.48e-10	1.23e+00	-0.2196
79784	MYH14	HTA11_3361_2000001011	Human	Colorectum	AD	3.87e-03	7.04e-01	-0.1207
79784	MYH14	HTA11_83_2000001011	Human	Colorectum	SER	2.65e-13	1.15e+00	-0.1526
79784	MYH14	HTA11_696_2000001011	Human	Colorectum	AD	6.81e-21	1.19e+00	-0.1464
79784	MYH14	HTA11_866_2000001011	Human	Colorectum	AD	1.10e-11	8.25e-01	-0.1001
79784	MYH14	HTA11_1391_2000001011	Human	Colorectum	AD	5.14e-06	8.45e-01	-0.059
79784	MYH14	HTA11_2992_2000001011	Human	Colorectum	SER	2.05e-04	7.49e-01	-0.1706
79784	MYH14	HTA11_546_2000001011	Human	Colorectum	AD	2.17e-06	7.72e-01	-0.0842

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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
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:00226045	Colorectum	CRC	regulation of cell morphogenesis	74/2078	309/18723	9.25e-11	5.04e-08	74
GO:00310324	Colorectum	CRC	actomyosin structure organization	45/2078	196/18723	1.49e-06	8.14e-05	45
GO:00083604	Colorectum	CRC	regulation of cell shape	38/2078	154/18723	1.51e-06	8.15e-05	38
GO:00015081	Colorectum	CRC	action potential	32/2078	134/18723	2.02e-05	5.90e-04	32
GO:00030123	Colorectum	CRC	muscle system process	74/2078	452/18723	3.92e-04	5.80e-03	74
GO:00705844	Colorectum	CRC	mitochondrion morphogenesis	8/2078	21/18723	1.22e-03	1.38e-02	8
GO:0035637	Colorectum	CRC	multicellular organismal signaling	31/2078	160/18723	1.39e-03	1.52e-02	31
GO:0060537	Colorectum	CRC	muscle tissue development	63/2078	403/18723	3.17e-03	2.78e-02	63
GO:0042391	Colorectum	CRC	regulation of membrane potential	67/2078	434/18723	3.27e-03	2.81e-02	67
GO:0014706	Colorectum	CRC	striated muscle tissue development	59/2078	384/18723	6.11e-03	4.47e-02	59
GO:002260415	Endometrium	AEH	regulation of cell morphogenesis	79/2100	309/18723	1.04e-12	2.24e-10	79
GO:00605376	Endometrium	AEH	muscle tissue development	83/2100	403/18723	2.57e-08	1.50e-06	83
GO:003103210	Endometrium	AEH	actomyosin structure organization	46/2100	196/18723	8.00e-07	2.91e-05	46
GO:00147065	Endometrium	AEH	striated muscle tissue development	75/2100	384/18723	1.06e-06	3.62e-05	75
GO:00300488	Endometrium	AEH	actin filament-based movement	31/2100	127/18723	2.10e-05	4.14e-04	31
GO:00030126	Endometrium	AEH	muscle system process	78/2100	452/18723	6.89e-05	1.06e-03	78
GO:00083609	Endometrium	AEH	regulation of cell shape	34/2100	154/18723	7.85e-05	1.18e-03	34
GO:00075174	Endometrium	AEH	muscle organ development	60/2100	327/18723	8.19e-05	1.22e-03	60
GO:0006936	Endometrium	AEH	muscle contraction	59/2100	347/18723	7.32e-04	6.99e-03	59
GO:00015083	Endometrium	AEH	action potential	26/2100	134/18723	3.66e-03	2.50e-02	26

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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
hsa0481016	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa0453020	Cervix	CC	Tight junction	49/1267	169/8465	1.87e-06	1.78e-05	1.05e-05	49
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0481017	Cervix	CC	Regulation of actin cytoskeleton	64/1267	229/8465	2.24e-07	2.59e-06	1.53e-06	64
hsa04530110	Cervix	CC	Tight junction	49/1267	169/8465	1.87e-06	1.78e-05	1.05e-05	49
hsa0513025	Cervix	HSIL_HPV	Pathogenic Escherichia coli infection	28/459	197/8465	2.36e-06	4.61e-05	3.73e-05	28
hsa0513035	Cervix	HSIL_HPV	Pathogenic Escherichia coli infection	28/459	197/8465	2.36e-06	4.61e-05	3.73e-05	28
hsa04530	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa045301	Colorectum	AD	Tight junction	76/2092	169/8465	5.49e-09	9.69e-08	6.18e-08	76
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa045302	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa051302	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60
hsa048102	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa045303	Colorectum	SER	Tight junction	59/1580	169/8465	3.24e-07	5.98e-06	4.34e-06	59
hsa051303	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60
hsa048103	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60

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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

MYH14

SNV

Missense_Mutation

c.5722N>T

p.Arg1908Trp

p.R1908W

Q7Z406

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-A2-A0D3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

MYH14

SNV

Missense_Mutation

c.4036N>A

p.Glu1346Lys

p.E1346K

Q7Z406

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYH14

SNV

Missense_Mutation

c.1067C>G

p.Thr356Arg

p.T356R

Q7Z406

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A0FJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

MYH14

SNV

Missense_Mutation

c.2846N>T

p.Arg949Leu

p.R949L

Q7Z406

protein_coding

tolerated(0.32)

benign(0.02)

TCGA-AN-A0FL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYH14

SNV

Missense_Mutation

novel

c.3631N>A

p.Gly1211Ser

p.G1211S

Q7Z406

protein_coding

tolerated(0.35)

benign(0.003)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

MYH14

SNV

Missense_Mutation

c.5599C>A

p.Arg1867Ser

p.R1867S

Q7Z406

protein_coding

deleterious(0.01)

possibly_damaging(0.807)

TCGA-AO-A124-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MYH14

SNV

Missense_Mutation

rs765142655

c.1463C>T

p.Ala488Val

p.A488V

Q7Z406

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MYH14

SNV

Missense_Mutation

c.2443N>T

p.Asp815Tyr

p.D815Y

Q7Z406

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AR-A254-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

MYH14

SNV

Missense_Mutation

rs751422907

c.5503N>T

p.Arg1835Cys

p.R1835C

Q7Z406

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B6-A0X5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYH14

SNV

Missense_Mutation

c.1811N>C

p.Val604Ala

p.V604A

Q7Z406

protein_coding

deleterious(0)

possibly_damaging(0.675)

TCGA-BH-A0DS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide

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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
79784	MYH14	NA		Mavacamten	MAVACAMTEN

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