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: MDFI

Gene summary for MDFI

Gene summary.

Gene information	Species	Human
	Gene symbol	MDFI
	Gene ID	4188
	Gene name	MyoD family inhibitor
	Gene Alias	I-MF
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024RCY2

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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
4188	MDFI	P42T-E	Human	Esophagus	ESCC	3.48e-23	5.78e-01	0.1175
4188	MDFI	P44T-E	Human	Esophagus	ESCC	2.00e-14	3.09e-01	0.1096
4188	MDFI	P47T-E	Human	Esophagus	ESCC	3.36e-19	5.08e-01	0.1067
4188	MDFI	P48T-E	Human	Esophagus	ESCC	1.15e-18	2.69e-01	0.0959
4188	MDFI	P49T-E	Human	Esophagus	ESCC	5.70e-16	1.58e+00	0.1768
4188	MDFI	P52T-E	Human	Esophagus	ESCC	2.10e-41	1.03e+00	0.1555
4188	MDFI	P54T-E	Human	Esophagus	ESCC	2.32e-08	1.73e-01	0.0975
4188	MDFI	P57T-E	Human	Esophagus	ESCC	1.37e-14	2.00e-01	0.0926
4188	MDFI	P61T-E	Human	Esophagus	ESCC	1.22e-12	2.41e-01	0.099
4188	MDFI	P62T-E	Human	Esophagus	ESCC	8.35e-43	8.46e-01	0.1302
4188	MDFI	P65T-E	Human	Esophagus	ESCC	3.23e-20	5.09e-01	0.0978
4188	MDFI	P74T-E	Human	Esophagus	ESCC	1.06e-31	9.81e-01	0.1479
4188	MDFI	P75T-E	Human	Esophagus	ESCC	1.42e-62	1.28e+00	0.1125
4188	MDFI	P76T-E	Human	Esophagus	ESCC	1.90e-61	1.36e+00	0.1207
4188	MDFI	P79T-E	Human	Esophagus	ESCC	3.62e-03	1.33e-01	0.1154
4188	MDFI	P80T-E	Human	Esophagus	ESCC	1.62e-46	1.22e+00	0.155
4188	MDFI	P82T-E	Human	Esophagus	ESCC	1.84e-13	8.88e-01	0.1072
4188	MDFI	P83T-E	Human	Esophagus	ESCC	3.75e-39	1.20e+00	0.1738
4188	MDFI	P84T-E	Human	Esophagus	ESCC	1.82e-03	1.88e-01	0.0933
4188	MDFI	P89T-E	Human	Esophagus	ESCC	8.31e-27	2.13e+00	0.1752

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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
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:00511019	Breast	Precancer	regulation of DNA binding	22/1080	118/18723	9.28e-07	3.71e-05	22
GO:00451859	Breast	Precancer	maintenance of protein location	19/1080	94/18723	1.43e-06	5.35e-05	19
GO:00510989	Breast	Precancer	regulation of binding	44/1080	363/18723	2.59e-06	8.65e-05	44
GO:00512358	Breast	Precancer	maintenance of location	40/1080	327/18723	5.85e-06	1.71e-04	40
GO:00018927	Breast	Precancer	embryonic placenta development	14/1080	82/18723	2.30e-04	3.48e-03	14
GO:00486087	Breast	Precancer	reproductive structure development	43/1080	424/18723	2.36e-04	3.56e-03	43
GO:00614587	Breast	Precancer	reproductive system development	43/1080	427/18723	2.75e-04	4.00e-03	43
GO:00018907	Breast	Precancer	placenta development	19/1080	144/18723	6.26e-04	7.78e-03	19
GO:00017017	Breast	Precancer	in utero embryonic development	35/1080	367/18723	2.47e-03	2.27e-02	35
GO:0060706	Breast	Precancer	cell differentiation involved in embryonic placenta development	6/1080	25/18723	2.49e-03	2.28e-02	6
GO:00511008	Breast	Precancer	negative regulation of binding	19/1080	162/18723	2.56e-03	2.32e-02	19
GO:00512203	Breast	Precancer	cytoplasmic sequestering of protein	5/1080	22/18723	7.32e-03	4.88e-02	5
GO:005109814	Breast	IDC	regulation of binding	57/1434	363/18723	1.59e-07	8.76e-06	57
GO:005110114	Breast	IDC	regulation of DNA binding	26/1434	118/18723	7.42e-07	3.40e-05	26
GO:004860812	Breast	IDC	reproductive structure development	60/1434	424/18723	2.71e-06	1.03e-04	60
GO:006145813	Breast	IDC	reproductive system development	60/1434	427/18723	3.41e-06	1.24e-04	60
GO:004518514	Breast	IDC	maintenance of protein location	21/1434	94/18723	6.69e-06	2.05e-04	21
GO:005123513	Breast	IDC	maintenance of location	48/1434	327/18723	9.90e-06	2.77e-04	48
GO:000189013	Breast	IDC	placenta development	25/1434	144/18723	9.19e-05	1.78e-03	25
GO:000189213	Breast	IDC	embryonic placenta development	16/1434	82/18723	4.28e-04	5.84e-03	16

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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

MDFI

SNV

Missense_Mutation

c.522C>G

p.Cys174Trp

p.C174W

Q99750

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A0J6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MDFI

insertion

Nonsense_Mutation

novel

c.637_638insTGGGATTACAGGCATGAGCCACTGGGCCCGGCCGACTTCTCTTA

p.Asp213ValfsTer6

p.D213Vfs*6

Q99750

protein_coding

TCGA-A2-A0CU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

MDFI

SNV

Missense_Mutation

c.500N>A

p.Cys167Tyr

p.C167Y

Q99750

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MDFI

SNV

Missense_Mutation

c.500N>A

p.Cys167Tyr

p.C167Y

Q99750

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-AG-3909-01

Colorectum

rectum adenocarcinoma

Female

>=65

III/IV

Chemotherapy

folinic

MDFI

SNV

Missense_Mutation

rs770572756

c.343N>T

p.Arg115Trp

p.R115W

Q99750

protein_coding

deleterious(0.03)

possibly_damaging(0.528)

TCGA-AJ-A3BG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

MDFI

SNV

Missense_Mutation

novel

c.446N>G

p.Lys149Arg

p.K149R

Q99750

protein_coding

tolerated(0.17)

benign(0.01)

TCGA-AX-A3G9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

MDFI

SNV

Missense_Mutation

rs768704952

c.382N>T

p.Arg128Trp

p.R128W

Q99750

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-B5-A11H-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Hormone Therapy

megace

MDFI

SNV

Missense_Mutation

rs753464609

c.170N>T

p.Ala57Val

p.A57V

Q99750

protein_coding

tolerated(0.88)

benign(0.003)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MDFI

SNV

Missense_Mutation

rs767995449

c.409N>A

p.Ala137Thr

p.A137T

Q99750

protein_coding

tolerated(0.68)

benign(0.009)

TCGA-D1-A167-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MDFI

SNV

Missense_Mutation

novel

c.371N>T

p.Pro124Leu

p.P124L

Q99750

protein_coding

deleterious(0)

benign(0.036)

TCGA-EY-A215-01

Endometrium

uterine corpus endometrioid 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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