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: MAST4

Gene summary for MAST4

Gene summary.

Gene information	Species	Human
	Gene symbol	MAST4
	Gene ID	375449
	Gene name	microtubule associated serine/threonine kinase family member 4
	Gene Alias	MAST4
	Cytomap	5q12.3
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	J3QT34

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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
375449	MAST4	RNA-P7T1-P7T1-1	Human	Lung	AIS	5.27e-14	1.25e+00	-0.0961
375449	MAST4	RNA-P7T1-P7T1-2	Human	Lung	AIS	1.72e-15	1.25e+00	-0.0876
375449	MAST4	RNA-P7T1-P7T1-3	Human	Lung	AIS	1.45e-11	1.19e+00	-0.0822
375449	MAST4	RNA-P7T1-P7T1-4	Human	Lung	AIS	3.77e-21	1.34e+00	-0.0809
375449	MAST4	RNA-P8T2-P8T2-1	Human	Lung	AIS	2.18e-03	1.44e+00	-0.1263
375449	MAST4	C04	Human	Oral cavity	OSCC	2.96e-14	9.85e-01	0.2633
375449	MAST4	C21	Human	Oral cavity	OSCC	2.01e-48	1.46e+00	0.2678
375449	MAST4	C30	Human	Oral cavity	OSCC	1.75e-21	1.14e+00	0.3055
375449	MAST4	C38	Human	Oral cavity	OSCC	2.58e-13	1.34e+00	0.172
375449	MAST4	C43	Human	Oral cavity	OSCC	6.34e-19	4.63e-01	0.1704
375449	MAST4	C46	Human	Oral cavity	OSCC	2.26e-37	9.41e-01	0.1673
375449	MAST4	C51	Human	Oral cavity	OSCC	9.21e-20	9.45e-01	0.2674
375449	MAST4	C57	Human	Oral cavity	OSCC	1.17e-18	8.47e-01	0.1679
375449	MAST4	C06	Human	Oral cavity	OSCC	1.20e-05	1.63e+00	0.2699
375449	MAST4	C07	Human	Oral cavity	OSCC	4.19e-04	1.10e+00	0.2491
375449	MAST4	C08	Human	Oral cavity	OSCC	3.21e-37	9.11e-01	0.1919
375449	MAST4	C86	Human	Oral cavity	OSCC	1.00e-02	1.04e+00	0.161
375449	MAST4	C09	Human	Oral cavity	OSCC	1.92e-50	2.20e+00	0.1431
375449	MAST4	LN22	Human	Oral cavity	OSCC	1.29e-06	1.12e+00	0.1733
375449	MAST4	LN46	Human	Oral cavity	OSCC	5.01e-34	1.18e+00	0.1666

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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
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
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:00181057	Cervix	CC	peptidyl-serine phosphorylation	63/2311	315/18723	6.65e-05	9.47e-04	63
GO:00182096	Cervix	CC	peptidyl-serine modification	66/2311	338/18723	9.58e-05	1.25e-03	66
GO:00181058	Endometrium	AEH	peptidyl-serine phosphorylation	50/2100	315/18723	7.20e-03	4.13e-02	50
GO:00182099	Esophagus	ESCC	peptidyl-serine modification	196/8552	338/18723	3.07e-06	3.47e-05	196
GO:001810515	Esophagus	ESCC	peptidyl-serine phosphorylation	184/8552	315/18723	3.22e-06	3.61e-05	184
GO:00181055	Liver	NAFLD	peptidyl-serine phosphorylation	63/1882	315/18723	7.45e-08	6.60e-06	63
GO:00182094	Liver	NAFLD	peptidyl-serine modification	64/1882	338/18723	4.65e-07	2.89e-05	64
GO:001810511	Liver	HCC	peptidyl-serine phosphorylation	169/7958	315/18723	3.86e-05	3.81e-04	169
GO:001820911	Liver	HCC	peptidyl-serine modification	177/7958	338/18723	1.45e-04	1.17e-03	177
GO:00181056	Lung	IAC	peptidyl-serine phosphorylation	69/2061	315/18723	1.48e-08	1.87e-06	69
GO:00182095	Lung	IAC	peptidyl-serine modification	70/2061	338/18723	1.23e-07	1.10e-05	70
GO:001810512	Lung	AIS	peptidyl-serine phosphorylation	60/1849	315/18723	4.75e-07	3.64e-05	60
GO:001820912	Lung	AIS	peptidyl-serine modification	61/1849	338/18723	2.49e-06	1.41e-04	61
GO:001810521	Lung	MIAC	peptidyl-serine phosphorylation	37/967	315/18723	2.73e-06	3.12e-04	37
GO:001820921	Lung	MIAC	peptidyl-serine modification	37/967	338/18723	1.38e-05	9.86e-04	37
GO:00182098	Oral cavity	OSCC	peptidyl-serine modification	175/7305	338/18723	1.09e-06	1.46e-05	175
GO:001810510	Oral cavity	OSCC	peptidyl-serine phosphorylation	164/7305	315/18723	1.51e-06	1.99e-05	164
GO:001810514	Oral cavity	EOLP	peptidyl-serine phosphorylation	84/2218	315/18723	3.32e-13	1.05e-10	84
GO:001820914	Oral cavity	EOLP	peptidyl-serine modification	87/2218	338/18723	1.07e-12	2.46e-10	87
GO:001810522	Oral cavity	NEOLP	peptidyl-serine phosphorylation	70/2005	315/18723	1.97e-09	1.24e-07	70

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

MAST4

SNV

Missense_Mutation

c.976N>G

p.His326Asp

p.H326D

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

MAST4

SNV

Missense_Mutation

novel

c.6466A>C

p.Ser2156Arg

p.S2156R

protein_coding

tolerated_low_confidence(0.05)

benign(0.029)

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

MAST4

SNV

Missense_Mutation

novel

c.1999N>A

p.Val667Ile

p.V667I

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A085-01

Breast

breast invasive carcinoma

Male

<65

I/II

Hormone Therapy

tamoxiphen

MAST4

SNV

Missense_Mutation

c.1279N>C

p.Asp427His

p.D427H

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAST4

SNV

Missense_Mutation

novel

c.4880N>T

p.Ala1627Val

p.A1627V

protein_coding

tolerated_low_confidence(0.28)

benign(0.003)

TCGA-AC-A8OQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAST4

SNV

Missense_Mutation

c.2599N>A

p.Asp867Asn

p.D867N

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0FZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

MAST4

SNV

Missense_Mutation

c.2614N>A

p.Asp872Asn

p.D872N

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MAST4

SNV

Missense_Mutation

c.2416N>A

p.Asp806Asn

p.D806N

protein_coding

deleterious(0.03)

probably_damaging(0.975)

TCGA-AR-A1AO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MAST4

SNV

Missense_Mutation

c.626N>T

p.Ser209Leu

p.S209L

protein_coding

deleterious_low_confidence(0.02)

benign(0.007)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MAST4

SNV

Missense_Mutation

c.1102G>A

p.Glu368Lys

p.E368K

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1J9-01

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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