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: EBF2

Gene summary for EBF2

Gene summary.

Gene information	Species	Human
	Gene symbol	EBF2
	Gene ID	64641
	Gene name	EBF transcription factor 2
	Gene Alias	COE2
	Cytomap	8p21.2
	Gene Type	protein-coding
	GO ID	GO:0001659
	UniProtAcc	B2RNT0

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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
64641	EBF2	ATC12	Human	Thyroid	ATC	4.23e-28	5.17e-01	0.34
64641	EBF2	ATC13	Human	Thyroid	ATC	1.88e-57	9.99e-01	0.34
64641	EBF2	ATC4	Human	Thyroid	ATC	2.45e-37	6.47e-01	0.34
64641	EBF2	ATC5	Human	Thyroid	ATC	1.85e-55	1.08e+00	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:19037498	Esophagus	ESCC	positive regulation of establishment of protein localization to mitochondrion	28/8552	36/18723	8.62e-05	6.22e-04	28
GO:190321415	Esophagus	ESCC	regulation of protein targeting to mitochondrion	32/8552	44/18723	2.50e-04	1.54e-03	32
GO:19026524	Esophagus	ESCC	secondary alcohol metabolic process	87/8552	147/18723	6.58e-04	3.50e-03	87
GO:19039556	Esophagus	ESCC	positive regulation of protein targeting to mitochondrion	24/8552	32/18723	7.22e-04	3.77e-03	24
GO:00085935	Esophagus	ESCC	regulation of Notch signaling pathway	59/8552	95/18723	9.12e-04	4.65e-03	59
GO:00329335	Esophagus	ESCC	SREBP signaling pathway	13/8552	15/18723	1.31e-03	6.26e-03	13
GO:00082034	Esophagus	ESCC	cholesterol metabolic process	79/8552	137/18723	3.11e-03	1.29e-02	79
GO:00715015	Esophagus	ESCC	cellular response to sterol depletion	13/8552	16/18723	4.05e-03	1.62e-02	13
GO:00161254	Esophagus	ESCC	sterol metabolic process	86/8552	152/18723	4.37e-03	1.73e-02	86
GO:00714986	Esophagus	ESCC	cellular response to fluid shear stress	16/8552	21/18723	4.47e-03	1.76e-02	16
GO:00344054	Esophagus	ESCC	response to fluid shear stress	24/8552	35/18723	5.25e-03	1.97e-02	24
GO:00069914	Esophagus	ESCC	response to sterol depletion	14/8552	18/18723	5.77e-03	2.14e-02	14
GO:00108836	Esophagus	ESCC	regulation of lipid storage	36/8552	57/18723	5.87e-03	2.17e-02	36
GO:007259412	Liver	Cirrhotic	establishment of protein localization to organelle	189/4634	422/18723	1.01e-19	2.45e-17	189
GO:00066057	Liver	Cirrhotic	protein targeting	148/4634	314/18723	3.86e-18	6.20e-16	148
GO:000820211	Liver	Cirrhotic	steroid metabolic process	143/4634	319/18723	2.79e-15	3.18e-13	143
GO:00224117	Liver	Cirrhotic	cellular component disassembly	182/4634	443/18723	1.59e-14	1.54e-12	182
GO:003238611	Liver	Cirrhotic	regulation of intracellular transport	147/4634	337/18723	1.84e-14	1.72e-12	147
GO:003315711	Liver	Cirrhotic	regulation of intracellular protein transport	108/4634	229/18723	1.23e-13	1.04e-11	108
GO:190382912	Liver	Cirrhotic	positive regulation of cellular protein localization	123/4634	276/18723	4.06e-13	3.22e-11	123

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
EBF2	ECM	Oral cavity	ADJ	PLAC9,EFHD1,MFAP5, etc.	7.18e-01
EBF2	ECM	Oral cavity	OSCC	PLAC9,EFHD1,MFAP5, etc.	1.13e-01

∗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

EBF2

SNV

Missense_Mutation

c.1373C>T

p.Pro458Leu

p.P458L

Q9HAK2

protein_coding

deleterious_low_confidence(0.04)

possibly_damaging(0.593)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

EBF2

SNV

Missense_Mutation

novel

c.202N>T

p.His68Tyr

p.H68Y

Q9HAK2

protein_coding

deleterious(0)

probably_damaging(0.911)

TCGA-AC-A2QI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

EBF2

SNV

Missense_Mutation

c.469N>A

p.Glu157Lys

p.E157K

Q9HAK2

protein_coding

deleterious(0)

possibly_damaging(0.6)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

EBF2

SNV

Missense_Mutation

c.1468N>G

p.Leu490Val

p.L490V

Q9HAK2

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.816)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

EBF2

SNV

Missense_Mutation

c.421N>A

p.Glu141Lys

p.E141K

Q9HAK2

protein_coding

deleterious(0.02)

probably_damaging(0.997)

TCGA-BH-A0DP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

EBF2

SNV

Missense_Mutation

novel

c.1204N>G

p.Leu402Val

p.L402V

Q9HAK2

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.911)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

EBF2

SNV

Missense_Mutation

novel

c.599C>G

p.Thr200Arg

p.T200R

Q9HAK2

protein_coding

deleterious(0)

benign(0.142)

TCGA-D8-A1JP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

EBF2

SNV

Missense_Mutation

novel

c.725N>C

p.Arg242Thr

p.R242T

Q9HAK2

protein_coding

deleterious(0)

possibly_damaging(0.491)

TCGA-EW-A423-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

EBF2

SNV

Missense_Mutation

novel

c.8N>A

p.Gly3Glu

p.G3E

Q9HAK2

protein_coding

deleterious_low_confidence(0.04)

benign(0.018)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

EBF2

SNV

Missense_Mutation

c.1138C>G

p.Leu380Val

p.L380V

Q9HAK2

protein_coding

tolerated(0.06)

benign(0.148)

TCGA-VS-A954-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

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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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