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: MAFB

Gene summary for MAFB

Gene summary.

Gene information	Species	Human
	Gene symbol	MAFB
	Gene ID	9935
	Gene name	MAF bZIP transcription factor B
	Gene Alias	DURS3
	Cytomap	20q12
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q9Y5Q3

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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
9935	MAFB	GSM4909280	Human	Breast	Precancer	5.81e-04	7.33e-01	0.0305
9935	MAFB	GSM4909282	Human	Breast	IDC	1.48e-27	7.71e-01	-0.0288
9935	MAFB	GSM4909286	Human	Breast	IDC	7.83e-11	-3.72e-01	0.1081
9935	MAFB	GSM4909287	Human	Breast	IDC	6.96e-03	-3.06e-01	0.2057
9935	MAFB	GSM4909296	Human	Breast	IDC	9.99e-03	-2.58e-01	0.1524
9935	MAFB	GSM4909298	Human	Breast	IDC	3.44e-02	-3.73e-02	0.1551
9935	MAFB	GSM4909301	Human	Breast	IDC	5.15e-08	-3.22e-01	0.1577
9935	MAFB	GSM4909311	Human	Breast	IDC	7.05e-10	-3.48e-01	0.1534
9935	MAFB	GSM4909312	Human	Breast	IDC	1.11e-02	-2.89e-01	0.1552
9935	MAFB	GSM4909319	Human	Breast	IDC	1.68e-09	-3.62e-01	0.1563
9935	MAFB	brca2	Human	Breast	Precancer	5.07e-03	-2.51e-01	-0.024
9935	MAFB	brca10	Human	Breast	Precancer	3.81e-04	-3.31e-01	-0.0029
9935	MAFB	P1	Human	Breast	IDC	1.33e-06	-3.05e-01	0.1527
9935	MAFB	DCIS2	Human	Breast	DCIS	1.05e-38	9.93e-02	0.0085
9935	MAFB	AEH-subject1	Human	Endometrium	AEH	1.96e-28	7.92e-01	-0.3059
9935	MAFB	AEH-subject2	Human	Endometrium	AEH	7.96e-15	5.48e-01	-0.2525
9935	MAFB	AEH-subject3	Human	Endometrium	AEH	1.77e-11	4.55e-01	-0.2576
9935	MAFB	EEC-subject2	Human	Endometrium	EEC	1.74e-06	3.53e-01	-0.2607
9935	MAFB	EEC-subject3	Human	Endometrium	EEC	1.04e-06	-1.35e-01	-0.2525
9935	MAFB	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	5.40e-03	-4.65e-02	-0.1869

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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
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:190210524	Skin	cSCC	regulation of leukocyte differentiation	92/4864	279/18723	5.20e-03	2.63e-02	92
GO:0045646110	Skin	cSCC	regulation of erythrocyte differentiation	20/4864	47/18723	9.84e-03	4.34e-02	20
GO:000276123	Skin	cSCC	regulation of myeloid leukocyte differentiation	43/4864	120/18723	1.06e-02	4.66e-02	43
GO:004211020	Thyroid	HT	T cell activation	63/1272	487/18723	5.95e-07	2.51e-05	63
GO:003410130	Thyroid	HT	erythrocyte homeostasis	24/1272	129/18723	5.57e-06	1.68e-04	24
GO:19031319	Thyroid	HT	mononuclear cell differentiation	54/1272	426/18723	6.88e-06	2.00e-04	54
GO:000226230	Thyroid	HT	myeloid cell homeostasis	27/1272	157/18723	6.97e-06	2.01e-04	27
GO:004887230	Thyroid	HT	homeostasis of number of cells	38/1272	272/18723	1.82e-05	4.31e-04	38
GO:190370627	Thyroid	HT	regulation of hemopoiesis	47/1272	367/18723	2.05e-05	4.68e-04	47
GO:004873228	Thyroid	HT	gland development	53/1272	436/18723	2.71e-05	5.97e-04	53
GO:00300986	Thyroid	HT	lymphocyte differentiation	47/1272	374/18723	3.32e-05	7.02e-04	47
GO:000268319	Thyroid	HT	negative regulation of immune system process	52/1272	434/18723	4.74e-05	9.49e-04	52
GO:004564624	Thyroid	HT	regulation of erythrocyte differentiation	12/1272	47/18723	5.17e-05	1.02e-03	12
GO:003021829	Thyroid	HT	erythrocyte differentiation	21/1272	120/18723	5.43e-05	1.06e-03	21
GO:003009930	Thyroid	HT	myeloid cell differentiation	45/1272	381/18723	2.07e-04	3.00e-03	45
GO:190210517	Thyroid	HT	regulation of leukocyte differentiation	35/1272	279/18723	3.32e-04	4.28e-03	35
GO:004563728	Thyroid	HT	regulation of myeloid cell differentiation	28/1272	210/18723	4.77e-04	5.78e-03	28
GO:004544417	Thyroid	HT	fat cell differentiation	29/1272	229/18723	8.88e-04	9.30e-03	29
GO:00302178	Thyroid	HT	T cell differentiation	31/1272	257/18723	1.35e-03	1.29e-02	31
GO:000257320	Thyroid	HT	myeloid leukocyte differentiation	24/1272	208/18723	7.69e-03	4.54e-02	24

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0492816	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0492817	Esophagus	ESCC	Parathyroid hormone synthesis, secretion and action	66/4205	106/8465	5.86e-03	1.47e-02	7.51e-03	66
hsa0492810	Lung	IAC	Parathyroid hormone synthesis, secretion and action	26/1053	106/8465	4.34e-04	4.03e-03	2.68e-03	26
hsa0492811	Lung	IAC	Parathyroid hormone synthesis, secretion and action	26/1053	106/8465	4.34e-04	4.03e-03	2.68e-03	26
hsa0492814	Prostate	BPH	Parathyroid hormone synthesis, secretion and action	33/1718	106/8465	5.30e-03	1.75e-02	1.08e-02	33
hsa0492815	Prostate	BPH	Parathyroid hormone synthesis, secretion and action	33/1718	106/8465	5.30e-03	1.75e-02	1.08e-02	33

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
MAFB	M1MAC	Breast	DCIS	FTL,TYROBP,FCER1G, etc.	1.07e-01
MAFB	DC	Breast	Healthy	FTL,TYROBP,FCER1G, etc.	3.69e-01
MAFB	M1MAC	Breast	Healthy	FTL,TYROBP,FCER1G, etc.	4.33e-02
MAFB	M1MAC	Breast	IDC	FTL,TYROBP,FCER1G, etc.	2.64e-01
MAFB	DC	Breast	IDC	FTL,TYROBP,FCER1G, etc.	9.78e-02
MAFB	INMON	Breast	IDC	FTL,TYROBP,FCER1G, etc.	1.51e-01
MAFB	MON	Breast	IDC	FTL,TYROBP,FCER1G, etc.	4.07e-02
MAFB	INMON	Breast	Precancer	FTL,TYROBP,FCER1G, etc.	3.13e-01
MAFB	ICAF	Cervix	CC	HEXIM1,LINC00324,LSMEM1, etc.	2.02e-01
MAFB	ICAF	Cervix	N_HPV	HEXIM1,LINC00324,LSMEM1, etc.	6.38e-02

∗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

MAFB

SNV

Missense_Mutation

novel

c.28G>A

p.Glu10Lys

p.E10K

Q9Y5Q3

protein_coding

deleterious(0.03)

benign(0.006)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

MAFB

SNV

Missense_Mutation

novel

c.107T>C

p.Leu36Pro

p.L36P

Q9Y5Q3

protein_coding

deleterious(0.02)

benign(0.003)

TCGA-AR-A1AJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAFB

insertion

In_Frame_Ins

novel

c.880_881insCTCACCCCATGGCCAATGGAATAGCAA

p.Tyr294delinsSerHisProMetAlaAsnGlyIleAlaAsn

p.Y294delinsSHPMANGIAN

Q9Y5Q3

protein_coding

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

MAFB

deletion

Frame_Shift_Del

novel

c.327delN

p.Ala110ArgfsTer115

p.A110Rfs*115

Q9Y5Q3

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MAFB

SNV

Missense_Mutation

c.801G>C

p.Glu267Asp

p.E267D

Q9Y5Q3

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

MAFB

SNV

Missense_Mutation

c.206N>G

p.Ser69Trp

p.S69W

Q9Y5Q3

protein_coding

deleterious(0.01)

possibly_damaging(0.761)

TCGA-MY-A5BF-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

MAFB

SNV

Missense_Mutation

c.229N>A

p.Glu77Lys

p.E77K

Q9Y5Q3

protein_coding

deleterious(0.03)

benign(0.108)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAFB

SNV

Missense_Mutation

c.296N>T

p.Ala99Val

p.A99V

Q9Y5Q3

protein_coding

tolerated(0.12)

benign(0.267)

TCGA-AA-3994-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

capecitabine

MAFB

SNV

Missense_Mutation

novel

c.373G>A

p.Asp125Asn

p.D125N

Q9Y5Q3

protein_coding

deleterious(0.04)

benign(0.188)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

MAFB

insertion

Frame_Shift_Ins

novel

c.882dupC

p.Lys295GlnfsTer51

p.K295Qfs*51

Q9Y5Q3

protein_coding

TCGA-AG-4022-01

Colorectum

rectum adenocarcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

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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
9935	MAFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		Tumor necrosis factor alpha (TNF-alpha) inhibitors

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