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: MYO5A

Gene summary for MYO5A

Gene summary.

Gene information	Species	Human
	Gene symbol	MYO5A
	Gene ID	4644
	Gene name	myosin VA
	Gene Alias	GS1
	Cytomap	15q21.2
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q9UES4

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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
4644	MYO5A	LZE4T	Human	Esophagus	ESCC	1.20e-11	4.39e-01	0.0811
4644	MYO5A	LZE7T	Human	Esophagus	ESCC	9.74e-03	3.00e-01	0.0667
4644	MYO5A	P2T-E	Human	Esophagus	ESCC	8.36e-10	6.83e-02	0.1177
4644	MYO5A	P4T-E	Human	Esophagus	ESCC	5.39e-13	1.71e-01	0.1323
4644	MYO5A	P5T-E	Human	Esophagus	ESCC	2.16e-14	1.14e-01	0.1327
4644	MYO5A	P8T-E	Human	Esophagus	ESCC	2.14e-07	4.80e-02	0.0889
4644	MYO5A	P9T-E	Human	Esophagus	ESCC	6.16e-06	1.44e-01	0.1131
4644	MYO5A	P10T-E	Human	Esophagus	ESCC	4.71e-10	2.24e-01	0.116
4644	MYO5A	P11T-E	Human	Esophagus	ESCC	2.14e-12	3.89e-01	0.1426
4644	MYO5A	P12T-E	Human	Esophagus	ESCC	2.03e-08	1.78e-01	0.1122
4644	MYO5A	P15T-E	Human	Esophagus	ESCC	3.28e-11	3.30e-01	0.1149
4644	MYO5A	P16T-E	Human	Esophagus	ESCC	7.69e-11	6.20e-02	0.1153
4644	MYO5A	P19T-E	Human	Esophagus	ESCC	2.62e-02	2.94e-01	0.1662
4644	MYO5A	P20T-E	Human	Esophagus	ESCC	5.10e-04	1.14e-01	0.1124
4644	MYO5A	P21T-E	Human	Esophagus	ESCC	1.53e-11	2.05e-01	0.1617
4644	MYO5A	P22T-E	Human	Esophagus	ESCC	9.93e-16	2.32e-01	0.1236
4644	MYO5A	P23T-E	Human	Esophagus	ESCC	3.32e-09	2.52e-01	0.108
4644	MYO5A	P24T-E	Human	Esophagus	ESCC	4.75e-07	1.44e-01	0.1287
4644	MYO5A	P26T-E	Human	Esophagus	ESCC	3.53e-18	3.61e-01	0.1276
4644	MYO5A	P27T-E	Human	Esophagus	ESCC	1.56e-07	7.52e-02	0.1055

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:005165617	Esophagus	ESCC	establishment of organelle localization	273/8552	390/18723	9.13e-23	1.81e-20	273
GO:0072659110	Esophagus	ESCC	protein localization to plasma membrane	193/8552	284/18723	1.95e-14	1.03e-12	193
GO:199077819	Esophagus	ESCC	protein localization to cell periphery	217/8552	333/18723	4.08e-13	1.88e-11	217
GO:000689215	Esophagus	ESCC	post-Golgi vesicle-mediated transport	82/8552	104/18723	4.00e-12	1.55e-10	82
GO:005165016	Esophagus	ESCC	establishment of vesicle localization	114/8552	161/18723	8.20e-11	2.53e-09	114
GO:003070518	Esophagus	ESCC	cytoskeleton-dependent intracellular transport	133/8552	195/18723	1.48e-10	4.27e-09	133
GO:005164815	Esophagus	ESCC	vesicle localization	119/8552	177/18723	5.16e-09	1.08e-07	119
GO:000701527	Esophagus	ESCC	actin filament organization	259/8552	442/18723	2.37e-08	4.50e-07	259
GO:190165319	Esophagus	ESCC	cellular response to peptide	208/8552	359/18723	1.68e-06	2.01e-05	208
GO:0043434111	Esophagus	ESCC	response to peptide hormone	234/8552	414/18723	4.93e-06	5.21e-05	234
GO:003286918	Esophagus	ESCC	cellular response to insulin stimulus	124/8552	203/18723	6.63e-06	6.75e-05	124
GO:003286818	Esophagus	ESCC	response to insulin	156/8552	264/18723	7.21e-06	7.20e-05	156
GO:00330593	Esophagus	ESCC	cellular pigmentation	40/8552	53/18723	9.67e-06	9.21e-05	40
GO:007137516	Esophagus	ESCC	cellular response to peptide hormone stimulus	166/8552	290/18723	4.48e-05	3.55e-04	166
GO:00995185	Esophagus	ESCC	vesicle cytoskeletal trafficking	50/8552	73/18723	6.75e-05	5.12e-04	50
GO:00434731	Esophagus	ESCC	pigmentation	59/8552	98/18723	2.64e-03	1.12e-02	59
GO:004819321	Liver	HCC	Golgi vesicle transport	217/7958	296/18723	2.58e-27	1.02e-24	217
GO:003286821	Liver	HCC	response to insulin	172/7958	264/18723	7.14e-14	4.23e-12	172
GO:003286921	Liver	HCC	cellular response to insulin stimulus	137/7958	203/18723	4.69e-13	2.44e-11	137

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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
hsa05130310	Esophagus	ESCC	Pathogenic Escherichia coli infection	142/4205	197/8465	8.21e-11	1.06e-09	5.42e-10	142
hsa0513042	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129
hsa0513052	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129
hsa0513030	Oral cavity	OSCC	Pathogenic Escherichia coli infection	129/3704	197/8465	4.32e-10	5.17e-09	2.63e-09	129
hsa05130114	Oral cavity	OSCC	Pathogenic Escherichia coli infection	129/3704	197/8465	4.32e-10	5.17e-09	2.63e-09	129
hsa0513045	Oral cavity	EOLP	Pathogenic Escherichia coli infection	54/1218	197/8465	1.10e-06	9.96e-06	5.87e-06	54
hsa0513055	Oral cavity	EOLP	Pathogenic Escherichia coli infection	54/1218	197/8465	1.10e-06	9.96e-06	5.87e-06	54
hsa0513063	Oral cavity	NEOLP	Pathogenic Escherichia coli infection	55/1112	197/8465	2.04e-08	4.32e-07	2.72e-07	55
hsa048145	Oral cavity	NEOLP	Motor proteins	37/1112	193/8465	1.06e-02	3.54e-02	2.22e-02	37
hsa0513073	Oral cavity	NEOLP	Pathogenic Escherichia coli infection	55/1112	197/8465	2.04e-08	4.32e-07	2.72e-07	55
hsa0481412	Oral cavity	NEOLP	Motor proteins	37/1112	193/8465	1.06e-02	3.54e-02	2.22e-02	37

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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

MYO5A

SNV

Missense_Mutation

novel

c.3088N>A

p.Glu1030Lys

p.E1030K

Q9Y4I1

protein_coding

tolerated(0.15)

benign(0.007)

TCGA-A2-A4S3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MYO5A

SNV

Missense_Mutation

c.3040N>C

p.Asp1014His

p.D1014H

Q9Y4I1

protein_coding

tolerated(0.07)

benign(0.01)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

MYO5A

SNV

Missense_Mutation

c.3578G>C

p.Arg1193Thr

p.R1193T

Q9Y4I1

protein_coding

tolerated(0.38)

benign(0)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYO5A

SNV

Missense_Mutation

rs751712752

c.5404C>T

p.Arg1802Cys

p.R1802C

Q9Y4I1

protein_coding

deleterious(0)

probably_damaging(0.931)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYO5A

SNV

Missense_Mutation

rs561485938

c.2438G>A

p.Arg813His

p.R813H

Q9Y4I1

protein_coding

deleterious(0)

possibly_damaging(0.815)

TCGA-BH-A1EN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MYO5A

SNV

Missense_Mutation

rs770697352

c.3361G>A

p.Glu1121Lys

p.E1121K

Q9Y4I1

protein_coding

tolerated(0.05)

benign(0.107)

TCGA-C8-A12Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

MYO5A

SNV

Missense_Mutation

novel

c.5122A>G

p.Lys1708Glu

p.K1708E

Q9Y4I1

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-E2-A1B1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Other, specify in notesbiphosphonate

zoledronic

MYO5A

insertion

Nonsense_Mutation

novel

c.3658_3659insGACATAACTTTAACTCCACAGACCTACGATAAGAATTT

p.Asn1220ArgfsTer11

p.N1220Rfs*11

Q9Y4I1

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MYO5A

insertion

Frame_Shift_Ins

novel

c.5465_5466insG

p.His1823ThrfsTer57

p.H1823Tfs*57

Q9Y4I1

protein_coding

TCGA-A7-A26I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

MYO5A

insertion

Frame_Shift_Ins

novel

c.5465_5466insG

p.His1823ThrfsTer57

p.H1823Tfs*57

Q9Y4I1

protein_coding

TCGA-AC-A3QQ-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

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