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: MAGEF1

Gene summary for MAGEF1

Gene summary.

Gene information	Species	Human
	Gene symbol	MAGEF1
	Gene ID	64110
	Gene name	MAGE family member F1
	Gene Alias	MAGE-F1
	Cytomap	3q27.1
	Gene Type	protein-coding
	GO ID	GO:0000018
	UniProtAcc	Q9HAY2

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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
64110	MAGEF1	GSM4909281	Human	Breast	IDC	7.04e-34	6.26e-01	0.21
64110	MAGEF1	GSM4909285	Human	Breast	IDC	2.13e-26	4.93e-01	0.21
64110	MAGEF1	GSM4909286	Human	Breast	IDC	1.28e-14	3.29e-01	0.1081
64110	MAGEF1	GSM4909293	Human	Breast	IDC	2.88e-06	2.43e-01	0.1581
64110	MAGEF1	GSM4909297	Human	Breast	IDC	2.91e-02	4.42e-02	0.1517
64110	MAGEF1	GSM4909298	Human	Breast	IDC	7.20e-06	1.93e-01	0.1551
64110	MAGEF1	GSM4909308	Human	Breast	IDC	7.15e-05	2.52e-01	0.158
64110	MAGEF1	GSM4909311	Human	Breast	IDC	5.34e-04	-1.03e-01	0.1534
64110	MAGEF1	GSM4909318	Human	Breast	IDC	1.75e-02	3.15e-01	0.2031
64110	MAGEF1	GSM4909319	Human	Breast	IDC	7.72e-09	-1.33e-01	0.1563
64110	MAGEF1	brca1	Human	Breast	Precancer	4.73e-02	1.45e-01	-0.0338
64110	MAGEF1	brca2	Human	Breast	Precancer	1.27e-07	2.18e-01	-0.024
64110	MAGEF1	brca3	Human	Breast	Precancer	4.44e-02	1.49e-01	-0.0263
64110	MAGEF1	M2	Human	Breast	IDC	3.17e-03	2.42e-01	0.21
64110	MAGEF1	NCCBC14	Human	Breast	DCIS	3.77e-03	9.09e-02	0.2021
64110	MAGEF1	P1	Human	Breast	IDC	2.54e-04	-1.22e-01	0.1527
64110	MAGEF1	P2	Human	Breast	IDC	3.51e-05	3.63e-01	0.21
64110	MAGEF1	DCIS2	Human	Breast	DCIS	3.77e-38	7.46e-02	0.0085
64110	MAGEF1	HTA11_3410_2000001011	Human	Colorectum	AD	2.15e-04	1.40e-01	0.0155
64110	MAGEF1	HTA11_78_2000001011	Human	Colorectum	AD	2.92e-05	2.02e-01	-0.1088

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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
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
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:00458629	Breast	Precancer	positive regulation of proteolysis	51/1080	372/18723	7.77e-09	5.70e-07	51
GO:19033629	Breast	Precancer	regulation of cellular protein catabolic process	36/1080	255/18723	6.03e-07	2.55e-05	36
GO:00421769	Breast	Precancer	regulation of protein catabolic process	47/1080	391/18723	1.50e-06	5.58e-05	47
GO:19030509	Breast	Precancer	regulation of proteolysis involved in cellular protein catabolic process	31/1080	221/18723	4.10e-06	1.27e-04	31
GO:00098969	Breast	Precancer	positive regulation of catabolic process	48/1080	492/18723	2.62e-04	3.84e-03	48
GO:00313319	Breast	Precancer	positive regulation of cellular catabolic process	43/1080	427/18723	2.75e-04	4.00e-03	43
GO:20000589	Breast	Precancer	regulation of ubiquitin-dependent protein catabolic process	21/1080	164/18723	5.00e-04	6.53e-03	21
GO:19033649	Breast	Precancer	positive regulation of cellular protein catabolic process	20/1080	155/18723	6.10e-04	7.67e-03	20
GO:19030527	Breast	Precancer	positive regulation of proteolysis involved in cellular protein catabolic process	17/1080	133/18723	1.68e-03	1.70e-02	17
GO:00457329	Breast	Precancer	positive regulation of protein catabolic process	25/1080	231/18723	1.87e-03	1.82e-02	25
GO:20010208	Breast	Precancer	regulation of response to DNA damage stimulus	24/1080	219/18723	1.93e-03	1.87e-02	24
GO:00516047	Breast	Precancer	protein maturation	28/1080	294/18723	6.45e-03	4.50e-02	28
GO:004586214	Breast	IDC	positive regulation of proteolysis	66/1434	372/18723	9.76e-11	1.29e-08	66
GO:004217614	Breast	IDC	regulation of protein catabolic process	63/1434	391/18723	1.32e-08	9.61e-07	63
GO:190336214	Breast	IDC	regulation of cellular protein catabolic process	46/1434	255/18723	4.00e-08	2.68e-06	46
GO:190305014	Breast	IDC	regulation of proteolysis involved in cellular protein catabolic process	41/1434	221/18723	9.77e-08	5.84e-06	41
GO:190336414	Breast	IDC	positive regulation of cellular protein catabolic process	29/1434	155/18723	5.93e-06	1.90e-04	29
GO:200005814	Breast	IDC	regulation of ubiquitin-dependent protein catabolic process	30/1434	164/18723	6.62e-06	2.05e-04	30
GO:004573214	Breast	IDC	positive regulation of protein catabolic process	37/1434	231/18723	1.46e-05	3.71e-04	37
GO:190305213	Breast	IDC	positive regulation of proteolysis involved in cellular protein catabolic process	25/1434	133/18723	2.34e-05	5.59e-04	25

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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

MAGEF1

SNV

Missense_Mutation

c.232N>G

p.Arg78Gly

p.R78G

Q9HAY2

protein_coding

tolerated(0.1)

possibly_damaging(0.685)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAGEF1

insertion

Nonsense_Mutation

novel

c.407_408insATTTAATACCTAAGATGAACTGGCTTTTTATGCTTTACT

p.Phe136delinsLeuPheAsnThrTerAspGluLeuAlaPheTyrAlaLeuLeu

p.F136delinsLFNT*DELAFYALL

Q9HAY2

protein_coding

TCGA-A8-A06Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAGEF1

insertion

In_Frame_Ins

novel

c.228_229insGGCGCGGTGGCTCACACCTGTAATCCC

p.Leu76_Asn77insGlyAlaValAlaHisThrCysAsnPro

p.L76_N77insGAVAHTCNP

Q9HAY2

protein_coding

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

MAGEF1

deletion

Frame_Shift_Del

novel

c.583delN

p.Arg195GlyfsTer83

p.R195Gfs*83

Q9HAY2

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

MAGEF1

SNV

Missense_Mutation

novel

c.271N>C

p.Asp91His

p.D91H

Q9HAY2

protein_coding

deleterious(0.04)

probably_damaging(0.996)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

MAGEF1

SNV

Missense_Mutation

c.46G>A

p.Glu16Lys

p.E16K

Q9HAY2

protein_coding

tolerated(0.27)

benign(0.003)

TCGA-EA-A3HT-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

MAGEF1

SNV

Missense_Mutation

c.671T>G

p.Leu224Arg

p.L224R

Q9HAY2

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-DY-A0XA-01

Colorectum

rectum adenocarcinoma

Female

<65

I/II

Chemotherapy

mayo

MAGEF1

SNV

Missense_Mutation

novel

c.149N>T

p.Ala50Val

p.A50V

Q9HAY2

protein_coding

tolerated(0.19)

benign(0)

TCGA-AP-A0LD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MAGEF1

SNV

Missense_Mutation

novel

c.491N>A

p.Gly164Asp

p.G164D

Q9HAY2

protein_coding

tolerated(0.12)

possibly_damaging(0.856)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MAGEF1

SNV

Missense_Mutation

novel

c.916C>A

p.Leu306Ile

p.L306I

Q9HAY2

protein_coding

tolerated_low_confidence(0.27)

benign(0.007)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

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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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