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:00458629	Breast	Precancer	positive regulation of proteolysis	51/1080	372/18723	7.77e-09	5.70e-07	51
GO:00509006	Breast	Precancer	leukocyte migration	47/1080	369/18723	2.82e-07	1.39e-05	47
GO:00341099	Breast	Precancer	homotypic cell-cell adhesion	18/1080	90/18723	3.15e-06	1.03e-04	18
GO:00300999	Breast	Precancer	myeloid cell differentiation	45/1080	381/18723	4.00e-06	1.25e-04	45
GO:00420609	Breast	Precancer	wound healing	48/1080	422/18723	5.48e-06	1.63e-04	48
GO:00421107	Breast	Precancer	T cell activation	52/1080	487/18723	1.37e-05	3.42e-04	52
GO:00106319	Breast	Precancer	epithelial cell migration	40/1080	357/18723	4.57e-05	9.71e-04	40
GO:00901329	Breast	Precancer	epithelium migration	40/1080	360/18723	5.51e-05	1.14e-03	40
GO:00025737	Breast	Precancer	myeloid leukocyte differentiation	27/1080	208/18723	6.72e-05	1.35e-03	27
GO:00435426	Breast	Precancer	endothelial cell migration	33/1080	279/18723	7.28e-05	1.44e-03	33
GO:00901309	Breast	Precancer	tissue migration	40/1080	365/18723	7.48e-05	1.47e-03	40
GO:00329709	Breast	Precancer	regulation of actin filament-based process	42/1080	397/18723	1.11e-04	2.01e-03	42
GO:00302248	Breast	Precancer	monocyte differentiation	9/1080	36/18723	1.56e-04	2.66e-03	9
GO:00508789	Breast	Precancer	regulation of body fluid levels	40/1080	379/18723	1.68e-04	2.77e-03	40
GO:00016678	Breast	Precancer	ameboidal-type cell migration	47/1080	475/18723	2.19e-04	3.35e-03	47
GO:19031313	Breast	Precancer	mononuclear cell differentiation	43/1080	426/18723	2.61e-04	3.84e-03	43
GO:00705278	Breast	Precancer	platelet aggregation	12/1080	67/18723	4.02e-04	5.43e-03	12
GO:00075995	Breast	Precancer	hemostasis	24/1080	222/18723	2.31e-03	2.15e-02	24
GO:00017017	Breast	Precancer	in utero embryonic development	35/1080	367/18723	2.47e-03	2.27e-02	35
GO:00075965	Breast	Precancer	blood coagulation	23/1080	217/18723	3.61e-03	2.98e-02	23

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05130211	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa04530211	Esophagus	ESCC	Tight junction	105/4205	169/8465	6.73e-04	2.23e-03	1.14e-03	105
hsa0481028	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa05130310	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa04530310	Esophagus	ESCC	Tight junction	105/4205	169/8465	6.73e-04	2.23e-03	1.14e-03	105
hsa04810112	Esophagus	ESCC	Regulation of actin cytoskeleton	133/4205	229/8465	5.94e-03	1.48e-02	7.56e-03	133
hsa0453022	Liver	Cirrhotic	Tight junction	82/2530	169/8465	2.14e-07	2.85e-06	1.76e-06	82
hsa0481021	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa0513022	Liver	Cirrhotic	Pathogenic Escherichia coli infection	88/2530	197/8465	6.48e-06	6.24e-05	3.84e-05	88
hsa0453032	Liver	Cirrhotic	Tight junction	82/2530	169/8465	2.14e-07	2.85e-06	1.76e-06	82
hsa0481031	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa0513032	Liver	Cirrhotic	Pathogenic Escherichia coli infection	88/2530	197/8465	6.48e-06	6.24e-05	3.84e-05	88
hsa0513042	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129
hsa0453042	Liver	HCC	Tight junction	110/4020	169/8465	2.45e-06	2.28e-05	1.27e-05	110
hsa0481041	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0513052	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129
hsa0453052	Liver	HCC	Tight junction	110/4020	169/8465	2.45e-06	2.28e-05	1.27e-05	110
hsa0481051	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0513062	Liver	Cyst	Pathogenic Escherichia coli infection	26/339	197/8465	6.98e-08	1.44e-06	1.19e-06	26
hsa0513072	Liver	Cyst	Pathogenic Escherichia coli infection	26/339	197/8465	6.98e-08	1.44e-06	1.19e-06	26

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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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