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: ETFB

Gene summary for ETFB

Gene summary.

Gene information	Species	Human
	Gene symbol	ETFB
	Gene ID	2109
	Gene name	electron transfer flavoprotein subunit beta
	Gene Alias	FP585
	Cytomap	19q13.41
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	P38117

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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
2109	ETFB	GSM4909285	Human	Breast	IDC	3.53e-33	7.07e-01	0.21
2109	ETFB	GSM4909294	Human	Breast	IDC	1.50e-11	3.71e-01	0.2022
2109	ETFB	GSM4909297	Human	Breast	IDC	2.01e-12	2.05e-01	0.1517
2109	ETFB	GSM4909304	Human	Breast	IDC	3.94e-23	5.13e-01	0.1636
2109	ETFB	GSM4909311	Human	Breast	IDC	1.57e-16	-2.65e-01	0.1534
2109	ETFB	GSM4909312	Human	Breast	IDC	3.01e-08	-2.42e-01	0.1552
2109	ETFB	GSM4909316	Human	Breast	IDC	2.85e-04	3.64e-01	0.21
2109	ETFB	GSM4909319	Human	Breast	IDC	5.69e-30	-2.06e-01	0.1563
2109	ETFB	GSM4909321	Human	Breast	IDC	4.46e-11	1.07e-01	0.1559
2109	ETFB	NCCBC14	Human	Breast	DCIS	4.34e-06	3.58e-02	0.2021
2109	ETFB	NCCBC5	Human	Breast	DCIS	1.11e-07	3.95e-02	0.2046
2109	ETFB	P1	Human	Breast	IDC	4.59e-11	-2.96e-01	0.1527
2109	ETFB	DCIS2	Human	Breast	DCIS	1.41e-58	2.79e-01	0.0085
2109	ETFB	CA_HPV_1	Human	Cervix	CC	1.22e-09	-2.61e-01	0.0264
2109	ETFB	CA_HPV_3	Human	Cervix	CC	2.74e-05	2.62e-01	0.0414
2109	ETFB	CCI_1	Human	Cervix	CC	5.91e-07	-5.24e-01	0.528
2109	ETFB	CCI_2	Human	Cervix	CC	7.08e-04	-5.02e-01	0.5249
2109	ETFB	CCI_3	Human	Cervix	CC	5.76e-04	-4.62e-01	0.516
2109	ETFB	CCII_1	Human	Cervix	CC	2.79e-05	-4.46e-01	0.3249
2109	ETFB	Tumor	Human	Cervix	CC	3.51e-09	3.29e-01	0.1241

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:000609113	Breast	IDC	generation of precursor metabolites and energy	103/1434	490/18723	1.53e-21	1.74e-18	103
GO:002290013	Breast	IDC	electron transport chain	51/1434	175/18723	2.23e-17	8.43e-15	51
GO:000609123	Breast	DCIS	generation of precursor metabolites and energy	103/1390	490/18723	1.46e-22	1.65e-19	103
GO:002290023	Breast	DCIS	electron transport chain	51/1390	175/18723	6.01e-18	2.62e-15	51
GO:00229009	Cervix	CC	electron transport chain	53/2311	175/18723	2.23e-10	3.43e-08	53
GO:00060919	Cervix	CC	generation of precursor metabolites and energy	105/2311	490/18723	7.40e-09	6.61e-07	105
GO:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0022900	Colorectum	AD	electron transport chain	89/3918	175/18723	1.42e-18	8.91e-16	89
GO:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0006635	Colorectum	AD	fatty acid beta-oxidation	33/3918	74/18723	3.98e-06	1.09e-04	33
GO:0009062	Colorectum	AD	fatty acid catabolic process	41/3918	100/18723	4.02e-06	1.09e-04	41
GO:0019395	Colorectum	AD	fatty acid oxidation	40/3918	103/18723	2.43e-05	4.69e-04	40
GO:0016042	Colorectum	AD	lipid catabolic process	97/3918	320/18723	4.31e-05	7.56e-04	97
GO:0006631	Colorectum	AD	fatty acid metabolic process	114/3918	390/18723	5.58e-05	9.44e-04	114
GO:0072329	Colorectum	AD	monocarboxylic acid catabolic process	44/3918	122/18723	8.05e-05	1.28e-03	44
GO:0034440	Colorectum	AD	lipid oxidation	40/3918	108/18723	8.52e-05	1.32e-03	40
GO:0030258	Colorectum	AD	lipid modification	67/3918	212/18723	1.66e-04	2.27e-03	67
GO:0016054	Colorectum	AD	organic acid catabolic process	73/3918	240/18723	3.20e-04	3.81e-03	73
GO:0044242	Colorectum	AD	cellular lipid catabolic process	66/3918	214/18723	3.96e-04	4.50e-03	66
GO:0046395	Colorectum	AD	carboxylic acid catabolic process	70/3918	236/18723	9.06e-04	8.71e-03	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

ETFB

SNV

Missense_Mutation

rs755539437

c.793N>T

p.Arg265Cys

p.R265C

P38117

protein_coding

tolerated_low_confidence(0.05)

probably_damaging(0.934)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ETFB

SNV

Missense_Mutation

rs104894677

c.764N>A

p.Arg255Gln

p.R255Q

P38117

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.983)

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ETFB

SNV

Missense_Mutation

c.1000G>A

p.Glu334Lys

p.E334K

P38117

protein_coding

tolerated_low_confidence(0.07)

benign(0.22)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

ETFB

SNV

Missense_Mutation

novel

c.991G>A

p.Glu331Lys

p.E331K

P38117

protein_coding

tolerated_low_confidence(0.14)

benign(0.305)

TCGA-C5-A3HF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ETFB

SNV

Missense_Mutation

c.284N>A

p.Ser95Tyr

p.S95Y

P38117

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-EA-A50E-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ETFB

SNV

Missense_Mutation

c.809C>T

p.Ala270Val

p.A270V

P38117

protein_coding

deleterious_low_confidence(0)

benign(0.092)

TCGA-A6-A565-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unspecific

5FU

ETFB

SNV

Missense_Mutation

c.523G>T

p.Asp175Tyr

p.D175Y

P38117

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

ETFB

SNV

Missense_Mutation

c.888G>T

p.Lys296Asn

p.K296N

P38117

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.868)

TCGA-CK-6751-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ETFB

SNV

Missense_Mutation

c.353C>A

p.Thr118Asn

p.T118N

P38117

protein_coding

deleterious_low_confidence(0)

benign(0.091)

TCGA-G5-6572-02

Colorectum

ETFB

SNV

Missense_Mutation

rs370522844

c.1033N>T

p.Arg345Trp

p.R345W

P38117

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.89)

TCGA-AP-A1DV-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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