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: ERRFI1

Gene summary for ERRFI1

Gene summary.

Gene information	Species	Human
	Gene symbol	ERRFI1
	Gene ID	54206
	Gene name	ERBB receptor feedback inhibitor 1
	Gene Alias	GENE-33
	Cytomap	1p36.23
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	B3KTV8

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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
54206	ERRFI1	GSM4909281	Human	Breast	IDC	1.32e-05	-3.41e-01	0.21
54206	ERRFI1	GSM4909282	Human	Breast	IDC	1.23e-06	-4.16e-01	-0.0288
54206	ERRFI1	GSM4909285	Human	Breast	IDC	2.09e-14	-5.09e-01	0.21
54206	ERRFI1	GSM4909286	Human	Breast	IDC	1.86e-10	-4.08e-01	0.1081
54206	ERRFI1	GSM4909287	Human	Breast	IDC	5.96e-11	-4.52e-01	0.2057
54206	ERRFI1	GSM4909288	Human	Breast	IDC	3.91e-03	-4.74e-01	0.0988
54206	ERRFI1	GSM4909290	Human	Breast	IDC	2.41e-11	-4.92e-01	0.2096
54206	ERRFI1	GSM4909291	Human	Breast	IDC	3.92e-07	-4.57e-01	0.1753
54206	ERRFI1	GSM4909293	Human	Breast	IDC	2.99e-09	-4.55e-01	0.1581
54206	ERRFI1	GSM4909294	Human	Breast	IDC	1.21e-23	-6.04e-01	0.2022
54206	ERRFI1	GSM4909296	Human	Breast	IDC	2.47e-23	-5.84e-01	0.1524
54206	ERRFI1	GSM4909297	Human	Breast	IDC	9.28e-17	-4.53e-01	0.1517
54206	ERRFI1	GSM4909298	Human	Breast	IDC	1.44e-18	-5.27e-01	0.1551
54206	ERRFI1	GSM4909301	Human	Breast	IDC	4.19e-02	-2.73e-01	0.1577
54206	ERRFI1	GSM4909306	Human	Breast	IDC	1.95e-18	-5.22e-01	0.1564
54206	ERRFI1	GSM4909307	Human	Breast	IDC	5.27e-15	-5.23e-01	0.1569
54206	ERRFI1	GSM4909308	Human	Breast	IDC	1.17e-08	-4.32e-01	0.158
54206	ERRFI1	GSM4909309	Human	Breast	IDC	5.60e-05	-2.94e-01	0.0483
54206	ERRFI1	GSM4909311	Human	Breast	IDC	1.57e-33	-6.15e-01	0.1534
54206	ERRFI1	GSM4909312	Human	Breast	IDC	5.88e-04	-2.17e-01	0.1552

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:000697014	Oral cavity	LP	response to osmotic stress	32/4623	84/18723	4.36e-03	2.79e-02	32
GO:190118513	Oral cavity	LP	negative regulation of ERBB signaling pathway	15/4623	32/18723	5.23e-03	3.19e-02	15
GO:190118412	Oral cavity	LP	regulation of ERBB signaling pathway	30/4623	79/18723	5.97e-03	3.54e-02	30
GO:003812716	Oral cavity	LP	ERBB signaling pathway	42/4623	121/18723	8.53e-03	4.61e-02	42
GO:006219718	Prostate	BPH	cellular response to chemical stress	110/3107	337/18723	2.44e-13	2.40e-11	110
GO:004854518	Prostate	BPH	response to steroid hormone	109/3107	339/18723	9.35e-13	8.15e-11	109
GO:007138316	Prostate	BPH	cellular response to steroid hormone stimulus	71/3107	204/18723	1.72e-10	9.79e-09	71
GO:004593618	Prostate	BPH	negative regulation of phosphate metabolic process	124/3107	441/18723	5.95e-10	2.90e-08	124
GO:001056318	Prostate	BPH	negative regulation of phosphorus metabolic process	124/3107	442/18723	6.94e-10	3.25e-08	124
GO:190165417	Prostate	BPH	response to ketone	67/3107	194/18723	8.10e-10	3.74e-08	67
GO:004232617	Prostate	BPH	negative regulation of phosphorylation	110/3107	385/18723	2.08e-09	8.35e-08	110
GO:190165310	Prostate	BPH	cellular response to peptide	104/3107	359/18723	2.51e-09	1.00e-07	104
GO:000193317	Prostate	BPH	negative regulation of protein phosphorylation	97/3107	342/18723	2.74e-08	8.11e-07	97
GO:00506739	Prostate	BPH	epithelial cell proliferation	116/3107	437/18723	7.12e-08	1.85e-06	116
GO:00506789	Prostate	BPH	regulation of epithelial cell proliferation	104/3107	381/18723	7.52e-08	1.92e-06	104
GO:005134818	Prostate	BPH	negative regulation of transferase activity	78/3107	268/18723	1.94e-07	4.29e-06	78
GO:004343417	Prostate	BPH	response to peptide hormone	109/3107	414/18723	2.73e-07	5.91e-06	109
GO:00713759	Prostate	BPH	cellular response to peptide hormone stimulus	82/3107	290/18723	3.65e-07	7.65e-06	82
GO:005138416	Prostate	BPH	response to glucocorticoid	49/3107	148/18723	6.20e-07	1.21e-05	49
GO:007084910	Prostate	BPH	response to epidermal growth factor	23/3107	49/18723	7.27e-07	1.38e-05	23

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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

ERRFI1

SNV

Missense_Mutation

rs750025751

c.777N>C

p.Lys259Asn

p.K259N

Q9UJM3

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-D8-A1X6-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

ERRFI1

insertion

Frame_Shift_Ins

novel

c.86dupT

p.Met29IlefsTer11

p.M29Ifs*11

Q9UJM3

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

ERRFI1

insertion

Frame_Shift_Ins

novel

c.84_85insCCTCCTCCACCTCAGACCCACCGAAGATTAAGAAGGTCTC

p.Met29ProfsTer24

p.M29Pfs*24

Q9UJM3

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

ERRFI1

insertion

Frame_Shift_Ins

novel

c.147_148insTTCTA

p.Ile50PhefsTer2

p.I50Ffs*2

Q9UJM3

protein_coding

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ERRFI1

insertion

Nonsense_Mutation

novel

c.146_147insTTTTCCCCTGTGCCCCTCTTTGTGAACGGG

p.Pro49_Ile50insPheProLeuCysProSerLeuTerThrGly

p.P49_I50insFPLCPSL*TG

Q9UJM3

protein_coding

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ERRFI1

SNV

Missense_Mutation

novel

c.1291G>A

p.Gly431Ser

p.G431S

Q9UJM3

protein_coding

tolerated_low_confidence(0.56)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ERRFI1

SNV

Missense_Mutation

rs781338553

c.1358G>A

p.Arg453His

p.R453H

Q9UJM3

protein_coding

deleterious_low_confidence(0)

benign(0.054)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ERRFI1

SNV

Missense_Mutation

rs746056102

c.731N>A

p.Arg244Gln

p.R244Q

Q9UJM3

protein_coding

deleterious(0.01)

benign(0.081)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

ERRFI1

SNV

Missense_Mutation

novel

c.763N>C

p.Gly255Arg

p.G255R

Q9UJM3

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AA-A02W-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ERRFI1

SNV

Missense_Mutation

rs779337445

c.1227N>T

p.Lys409Asn

p.K409N

Q9UJM3

protein_coding

deleterious(0)

possibly_damaging(0.796)

TCGA-AD-6895-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

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
54206	ERRFI1	CLINICALLY ACTIONABLE		ERLOTINIB	ERLOTINIB	24550739
54206	ERRFI1	CLINICALLY ACTIONABLE		EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITOR		23935914

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