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: ACTG1

Gene summary for ACTG1

Gene summary.

Gene information	Species	Human
	Gene symbol	ACTG1
	Gene ID	71
	Gene name	actin gamma 1
	Gene Alias	ACT
	Cytomap	17q25.3
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	P63261

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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
71	ACTG1	GSM4909287	Human	Breast	IDC	1.11e-04	1.15e-01	0.2057
71	ACTG1	GSM4909288	Human	Breast	IDC	1.63e-11	3.43e-01	0.0988
71	ACTG1	GSM4909293	Human	Breast	IDC	5.90e-42	3.34e-01	0.1581
71	ACTG1	GSM4909294	Human	Breast	IDC	7.93e-03	-8.81e-02	0.2022
71	ACTG1	GSM4909295	Human	Breast	IDC	4.03e-05	2.33e-01	0.0898
71	ACTG1	GSM4909296	Human	Breast	IDC	1.20e-42	-8.02e-01	0.1524
71	ACTG1	GSM4909297	Human	Breast	IDC	5.18e-07	-4.20e-02	0.1517
71	ACTG1	GSM4909298	Human	Breast	IDC	6.41e-09	1.56e-01	0.1551
71	ACTG1	GSM4909301	Human	Breast	IDC	1.76e-06	-2.82e-01	0.1577
71	ACTG1	GSM4909311	Human	Breast	IDC	1.68e-32	-6.23e-01	0.1534
71	ACTG1	GSM4909317	Human	Breast	IDC	3.10e-23	3.13e-01	0.1355
71	ACTG1	GSM4909318	Human	Breast	IDC	3.01e-05	3.09e-01	0.2031
71	ACTG1	GSM4909319	Human	Breast	IDC	4.98e-40	-3.62e-01	0.1563
71	ACTG1	GSM4909320	Human	Breast	IDC	2.09e-03	-2.89e-01	0.1575
71	ACTG1	GSM4909321	Human	Breast	IDC	9.41e-54	3.64e-01	0.1559
71	ACTG1	ctrl6	Human	Breast	Precancer	1.13e-04	2.42e-01	-0.0061
71	ACTG1	brca1	Human	Breast	Precancer	8.89e-38	3.59e-01	-0.0338
71	ACTG1	brca3	Human	Breast	Precancer	1.63e-16	2.39e-01	-0.0263
71	ACTG1	brca7	Human	Breast	Precancer	5.10e-03	2.92e-01	-0.009
71	ACTG1	brca10	Human	Breast	Precancer	2.71e-22	2.95e-01	-0.0029

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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
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:00341099	Breast	Precancer	homotypic cell-cell adhesion	18/1080	90/18723	3.15e-06	1.03e-04	18
GO:00420609	Breast	Precancer	wound healing	48/1080	422/18723	5.48e-06	1.63e-04	48
GO:19029039	Breast	Precancer	regulation of supramolecular fiber organization	42/1080	383/18723	4.92e-05	1.04e-03	42
GO:00329709	Breast	Precancer	regulation of actin filament-based process	42/1080	397/18723	1.11e-04	2.01e-03	42
GO:00508789	Breast	Precancer	regulation of body fluid levels	40/1080	379/18723	1.68e-04	2.77e-03	40
GO:00070159	Breast	Precancer	actin filament organization	44/1080	442/18723	3.02e-04	4.35e-03	44
GO:00705278	Breast	Precancer	platelet aggregation	12/1080	67/18723	4.02e-04	5.43e-03	12
GO:00356335	Breast	Precancer	maintenance of blood-brain barrier	8/1080	35/18723	6.95e-04	8.43e-03	8
GO:19030367	Breast	Precancer	positive regulation of response to wounding	12/1080	72/18723	7.90e-04	9.30e-03	12
GO:00329569	Breast	Precancer	regulation of actin cytoskeleton organization	36/1080	358/18723	8.56e-04	9.88e-03	36
GO:01100539	Breast	Precancer	regulation of actin filament organization	29/1080	278/18723	1.50e-03	1.55e-02	29
GO:00018956	Breast	Precancer	retina homeostasis	12/1080	79/18723	1.82e-03	1.79e-02	12
GO:00903036	Breast	Precancer	positive regulation of wound healing	10/1080	59/18723	1.86e-03	1.81e-02	10
GO:00514929	Breast	Precancer	regulation of stress fiber assembly	13/1080	91/18723	2.11e-03	2.00e-02	13
GO:00075995	Breast	Precancer	hemostasis	24/1080	222/18723	2.31e-03	2.15e-02	24
GO:00300389	Breast	Precancer	contractile actin filament bundle assembly	14/1080	106/18723	3.07e-03	2.62e-02	14
GO:00431499	Breast	Precancer	stress fiber assembly	14/1080	106/18723	3.07e-03	2.62e-02	14
GO:00018948	Breast	Precancer	tissue homeostasis	27/1080	268/18723	3.49e-03	2.90e-02	27
GO:19030348	Breast	Precancer	regulation of response to wounding	19/1080	167/18723	3.60e-03	2.98e-02	19
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
hsa05416	Colorectum	MSI-H	Viral myocarditis	14/797	60/8465	1.09e-03	1.20e-02	1.01e-02	14
hsa054186	Colorectum	MSI-H	Fluid shear stress and atherosclerosis	25/797	139/8465	1.11e-03	1.20e-02	1.01e-02	25
hsa051306	Colorectum	MSI-H	Pathogenic Escherichia coli infection	31/797	197/8465	2.90e-03	2.93e-02	2.46e-02	31
hsa049196	Colorectum	MSI-H	Thyroid hormone signaling pathway	21/797	121/8465	4.18e-03	4.10e-02	3.44e-02	21
hsa051006	Colorectum	MSI-H	Bacterial invasion of epithelial cells	15/797	77/8465	4.86e-03	4.63e-02	3.88e-02	15
hsa050147	Colorectum	MSI-H	Amyotrophic lateral sclerosis	95/797	364/8465	2.31e-21	1.50e-19	1.26e-19	95
hsa047147	Colorectum	MSI-H	Thermogenesis	56/797	232/8465	1.79e-11	4.14e-10	3.47e-10	56
hsa051107	Colorectum	MSI-H	Vibrio cholerae infection	18/797	50/8465	2.77e-07	5.61e-06	4.70e-06	18
hsa045207	Colorectum	MSI-H	Adherens junction	22/797	93/8465	3.71e-05	5.47e-04	4.58e-04	22
hsa051327	Colorectum	MSI-H	Salmonella infection	43/797	249/8465	5.91e-05	8.33e-04	6.98e-04	43
hsa045307	Colorectum	MSI-H	Tight junction	31/797	169/8465	2.08e-04	2.80e-03	2.35e-03	31
hsa051317	Colorectum	MSI-H	Shigellosis	40/797	247/8465	4.28e-04	5.34e-03	4.47e-03	40
hsa041451	Colorectum	MSI-H	Phagosome	27/797	152/8465	8.74e-04	1.01e-02	8.48e-03	27
hsa054161	Colorectum	MSI-H	Viral myocarditis	14/797	60/8465	1.09e-03	1.20e-02	1.01e-02	14
hsa054187	Colorectum	MSI-H	Fluid shear stress and atherosclerosis	25/797	139/8465	1.11e-03	1.20e-02	1.01e-02	25
hsa051307	Colorectum	MSI-H	Pathogenic Escherichia coli infection	31/797	197/8465	2.90e-03	2.93e-02	2.46e-02	31
hsa049197	Colorectum	MSI-H	Thyroid hormone signaling pathway	21/797	121/8465	4.18e-03	4.10e-02	3.44e-02	21
hsa051007	Colorectum	MSI-H	Bacterial invasion of epithelial cells	15/797	77/8465	4.86e-03	4.63e-02	3.88e-02	15
hsa045208	Colorectum	FAP	Adherens junction	45/1404	93/8465	8.66e-13	2.89e-10	1.76e-10	45
hsa045308	Colorectum	FAP	Tight junction	60/1404	169/8465	1.40e-09	9.33e-08	5.67e-08	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

ACTG1

SNV

Missense_Mutation

novel

c.83G>T

p.Arg28Leu

p.R28L

P63261

protein_coding

deleterious_low_confidence(0.01)

benign(0)

TCGA-AC-A2BK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

ACTG1

SNV

Missense_Mutation

novel

c.356N>C

p.Met119Thr

p.M119T

P63261

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.969)

TCGA-AC-A3QP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

ACTG1

SNV

Missense_Mutation

novel

c.242N>G

p.Asp81Gly

p.D81G

P63261

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.998)

TCGA-C8-A3M8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

ACTG1

SNV

Missense_Mutation

c.727C>G

p.Pro243Ala

p.P243A

P63261

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.951)

TCGA-D8-A146-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ACTG1

SNV

Missense_Mutation

c.614N>G

p.Glu205Gly

p.E205G

P63261

protein_coding

deleterious_low_confidence(0.01)

benign(0.201)

TCGA-E2-A1LS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cyclophosphamide

ACTG1

insertion

Nonsense_Mutation

novel

c.170_171insTGCACACACCTCATGCTAGCCTCACGAAACT

p.Glu57AspfsTer7

p.E57Dfs*7

P63261

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ACTG1

insertion

Frame_Shift_Ins

novel

c.379_380insCCCCCACGCCATCCTGCGTCTG

p.Phe127SerfsTer76

p.F127Sfs*76

P63261

protein_coding

TCGA-A8-A093-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ACTG1

insertion

Frame_Shift_Ins

novel

c.983_984insCGTGCTTGTGGAAGACAAGTCTGTGGCTT

p.Lys328AsnfsTer11

p.K328Nfs*11

P63261

protein_coding

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ACTG1

SNV

Missense_Mutation

novel

c.965N>T

p.Pro322Leu

p.P322L

P63261

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.466)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ACTG1

SNV

Missense_Mutation

c.757N>A

p.Glu253Lys

p.E253K

P63261

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.999)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

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
71	ACTG1	NA		vincristine	VINCRISTINE
71	ACTG1	NA		THYMOSIN BETA-4

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