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: MYH9

Gene summary for MYH9

Gene summary.

Gene information	Species	Human
	Gene symbol	MYH9
	Gene ID	4627
	Gene name	myosin heavy chain 9
	Gene Alias	BDPLT6
	Cytomap	22q12.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024R1N1

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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
4627	MYH9	GSM4909281	Human	Breast	IDC	1.58e-18	5.40e-01	0.21
4627	MYH9	GSM4909285	Human	Breast	IDC	3.92e-10	-4.37e-01	0.21
4627	MYH9	GSM4909286	Human	Breast	IDC	2.55e-02	-3.26e-01	0.1081
4627	MYH9	GSM4909294	Human	Breast	IDC	1.38e-05	-3.24e-01	0.2022
4627	MYH9	GSM4909296	Human	Breast	IDC	7.96e-11	-3.53e-01	0.1524
4627	MYH9	GSM4909297	Human	Breast	IDC	8.22e-18	-4.03e-01	0.1517
4627	MYH9	GSM4909298	Human	Breast	IDC	4.99e-02	-2.75e-01	0.1551
4627	MYH9	GSM4909301	Human	Breast	IDC	4.50e-06	-3.60e-01	0.1577
4627	MYH9	GSM4909306	Human	Breast	IDC	5.31e-08	-3.77e-01	0.1564
4627	MYH9	GSM4909308	Human	Breast	IDC	4.54e-04	-2.95e-01	0.158
4627	MYH9	GSM4909311	Human	Breast	IDC	8.92e-32	-3.19e-01	0.1534
4627	MYH9	GSM4909312	Human	Breast	IDC	2.30e-14	-3.54e-01	0.1552
4627	MYH9	GSM4909313	Human	Breast	IDC	3.94e-03	-2.42e-01	0.0391
4627	MYH9	GSM4909319	Human	Breast	IDC	7.67e-33	-5.41e-01	0.1563
4627	MYH9	GSM4909320	Human	Breast	IDC	9.34e-10	-4.70e-01	0.1575
4627	MYH9	GSM4909321	Human	Breast	IDC	1.40e-29	-5.25e-01	0.1559
4627	MYH9	brca1	Human	Breast	Precancer	3.22e-03	2.39e-01	-0.0338
4627	MYH9	brca3	Human	Breast	Precancer	8.78e-14	4.94e-01	-0.0263
4627	MYH9	brca10	Human	Breast	Precancer	7.49e-03	3.42e-01	-0.0029
4627	MYH9	NCCBC14	Human	Breast	DCIS	6.39e-14	-2.06e-02	0.2021

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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
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
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
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:00426924	Cervix	CC	muscle cell differentiation	69/2311	384/18723	8.12e-04	7.09e-03	69
GO:00301682	Cervix	CC	platelet activation	28/2311	123/18723	8.92e-04	7.71e-03	28
GO:00075996	Cervix	CC	hemostasis	44/2311	222/18723	9.47e-04	7.95e-03	44
GO:0000768	Cervix	CC	syncytium formation by plasma membrane fusion	15/2311	55/18723	2.14e-03	1.54e-02	15
GO:0140253	Cervix	CC	cell-cell fusion	15/2311	55/18723	2.14e-03	1.54e-02	15
GO:00069491	Cervix	CC	syncytium formation	15/2311	57/18723	3.13e-03	2.05e-02	15
GO:00511464	Cervix	CC	striated muscle cell differentiation	50/2311	283/18723	5.53e-03	3.19e-02	50
GO:0006909	Cervix	CC	phagocytosis	53/2311	308/18723	7.49e-03	4.01e-02	53
GO:00070092	Cervix	CC	plasma membrane organization	28/2311	142/18723	7.85e-03	4.14e-02	28
GO:00068873	Cervix	CC	exocytosis	59/2311	352/18723	8.74e-03	4.48e-02	59
GO:00510143	Cervix	CC	actin filament severing	6/2311	16/18723	9.35e-03	4.66e-02	6
GO:00103243	Cervix	CC	membrane invagination	28/2311	144/18723	9.50e-03	4.72e-02	28
GO:00302249	Cervix	CC	monocyte differentiation	10/2311	36/18723	9.87e-03	4.85e-02	10
GO:0032970	Colorectum	AD	regulation of actin filament-based process	142/3918	397/18723	4.05e-12	5.90e-10	142
GO:0045862	Colorectum	AD	positive regulation of proteolysis	129/3918	372/18723	4.04e-10	3.46e-08	129
GO:0051656	Colorectum	AD	establishment of organelle localization	131/3918	390/18723	3.00e-09	2.06e-07	131
GO:0022604	Colorectum	AD	regulation of cell morphogenesis	109/3918	309/18723	3.08e-09	2.07e-07	109
GO:0034109	Colorectum	AD	homotypic cell-cell adhesion	40/3918	90/18723	4.37e-07	1.67e-05	40
GO:0007163	Colorectum	AD	establishment or maintenance of cell polarity	77/3918	218/18723	5.72e-07	2.08e-05	77
GO:0030099	Colorectum	AD	myeloid cell differentiation	119/3918	381/18723	1.24e-06	4.01e-05	119

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513018	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0453018	Breast	Precancer	Tight junction	31/684	169/8465	1.13e-05	1.26e-04	9.64e-05	31
hsa0513019	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0453019	Breast	Precancer	Tight junction	31/684	169/8465	1.13e-05	1.26e-04	9.64e-05	31
hsa0453024	Breast	IDC	Tight junction	38/867	169/8465	2.07e-06	3.20e-05	2.39e-05	38
hsa0513024	Breast	IDC	Pathogenic Escherichia coli infection	42/867	197/8465	2.66e-06	3.92e-05	2.94e-05	42
hsa0481014	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0453034	Breast	IDC	Tight junction	38/867	169/8465	2.07e-06	3.20e-05	2.39e-05	38
hsa0513034	Breast	IDC	Pathogenic Escherichia coli infection	42/867	197/8465	2.66e-06	3.92e-05	2.94e-05	42
hsa0481015	Breast	IDC	Regulation of actin cytoskeleton	36/867	229/8465	5.79e-03	3.13e-02	2.34e-02	36
hsa0513043	Breast	DCIS	Pathogenic Escherichia coli infection	42/846	197/8465	1.40e-06	2.15e-05	1.59e-05	42
hsa0453044	Breast	DCIS	Tight junction	37/846	169/8465	3.07e-06	4.20e-05	3.09e-05	37
hsa0481023	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
hsa0513053	Breast	DCIS	Pathogenic Escherichia coli infection	42/846	197/8465	1.40e-06	2.15e-05	1.59e-05	42
hsa0453054	Breast	DCIS	Tight junction	37/846	169/8465	3.07e-06	4.20e-05	3.09e-05	37
hsa0481033	Breast	DCIS	Regulation of actin cytoskeleton	35/846	229/8465	6.89e-03	3.37e-02	2.48e-02	35
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

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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

MYH9

SNV

Missense_Mutation

novel

c.2176C>T

p.Pro726Ser

p.P726S

P35579

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-5L-AAT0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MYH9

SNV

Missense_Mutation

novel

c.1393N>C

p.Glu465Gln

p.E465Q

P35579

protein_coding

deleterious(0)

possibly_damaging(0.823)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

MYH9

SNV

Missense_Mutation

c.3031N>C

p.Glu1011Gln

p.E1011Q

P35579

protein_coding

deleterious(0.02)

probably_damaging(0.973)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MYH9

SNV

Missense_Mutation

rs371410108

c.4975G>A

p.Ala1659Thr

p.A1659T

P35579

protein_coding

tolerated(0.33)

benign(0.045)

TCGA-A7-A4SC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MYH9

SNV

Missense_Mutation

novel

c.2843N>G

p.Leu948Arg

p.L948R

P35579

protein_coding

deleterious(0)

probably_damaging(0.976)

TCGA-A8-A07P-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

MYH9

SNV

Missense_Mutation

c.274N>G

p.Leu92Val

p.L92V

P35579

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYH9

SNV

Missense_Mutation

c.3341N>G

p.Ser1114Cys

p.S1114C

P35579

protein_coding

deleterious(0.01)

possibly_damaging(0.676)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYH9

SNV

Missense_Mutation

rs140032888

c.2221G>A

p.Val741Met

p.V741M

P35579

protein_coding

tolerated(0.08)

benign(0.125)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYH9

SNV

Missense_Mutation

c.3086N>C

p.Ile1029Thr

p.I1029T

P35579

protein_coding

deleterious(0.01)

possibly_damaging(0.71)

TCGA-AQ-A7U7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Targeted Molecular therapy

rituximab

MYH9

SNV

Missense_Mutation

novel

c.1492N>A

p.Glu498Lys

p.E498K

P35579

protein_coding

deleterious(0.04)

benign(0.345)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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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