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: TMEM131

Gene summary for TMEM131

Gene summary.

Gene information	Species	Human
	Gene symbol	TMEM131
	Gene ID	23505
	Gene name	transmembrane protein 131
	Gene Alias	CC28
	Cytomap	2q11.2
	Gene Type	protein-coding
	GO ID	GO:0008150
	UniProtAcc	Q92545

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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
23505	TMEM131	CCI_2	Human	Cervix	CC	2.37e-05	9.47e-01	0.5249
23505	TMEM131	CCI_3	Human	Cervix	CC	1.30e-05	6.44e-01	0.516
23505	TMEM131	HTA11_3410_2000001011	Human	Colorectum	AD	2.17e-26	-7.74e-01	0.0155
23505	TMEM131	HTA11_2951_2000001011	Human	Colorectum	AD	3.18e-03	-8.30e-01	0.0216
23505	TMEM131	HTA11_347_2000001011	Human	Colorectum	AD	3.75e-10	4.99e-01	-0.1954
23505	TMEM131	HTA11_3361_2000001011	Human	Colorectum	AD	5.25e-03	-3.97e-01	-0.1207
23505	TMEM131	HTA11_5212_2000001011	Human	Colorectum	AD	9.99e-04	-4.68e-01	-0.2061
23505	TMEM131	HTA11_9341_2000001011	Human	Colorectum	SER	1.76e-02	-7.22e-01	-0.00410000000000005
23505	TMEM131	HTA11_7862_2000001011	Human	Colorectum	AD	1.46e-02	-5.40e-01	-0.0179
23505	TMEM131	HTA11_866_3004761011	Human	Colorectum	AD	4.02e-04	-4.59e-01	0.096
23505	TMEM131	HTA11_8622_2000001021	Human	Colorectum	SER	1.62e-04	-5.43e-01	0.0528
23505	TMEM131	HTA11_10711_2000001011	Human	Colorectum	AD	6.10e-05	-5.77e-01	0.0338
23505	TMEM131	HTA11_7696_3000711011	Human	Colorectum	AD	1.06e-10	-5.09e-01	0.0674
23505	TMEM131	HTA11_6818_2000001011	Human	Colorectum	AD	1.81e-04	-6.59e-01	0.0112
23505	TMEM131	HTA11_6818_2000001021	Human	Colorectum	AD	3.94e-08	-5.63e-01	0.0588
23505	TMEM131	HTA11_99999970781_79442	Human	Colorectum	MSS	1.02e-06	-3.91e-01	0.294
23505	TMEM131	HTA11_99999971662_82457	Human	Colorectum	MSS	9.50e-03	-3.46e-01	0.3859
23505	TMEM131	HTA11_99999973899_84307	Human	Colorectum	MSS	3.99e-03	-5.81e-01	0.2585
23505	TMEM131	HTA11_99999974143_84620	Human	Colorectum	MSS	1.71e-21	-6.54e-01	0.3005
23505	TMEM131	A001-C-207	Human	Colorectum	FAP	2.94e-02	-1.84e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:002240710	Cervix	CC	regulation of cell-cell adhesion	103/2311	448/18723	1.78e-10	2.87e-08	103
GO:00421108	Cervix	CC	T cell activation	107/2311	487/18723	1.24e-09	1.46e-07	107
GO:00508638	Cervix	CC	regulation of T cell activation	80/2311	329/18723	1.28e-09	1.47e-07	80
GO:00160557	Cervix	CC	Wnt signaling pathway	98/2311	444/18723	4.82e-09	4.65e-07	98
GO:01987387	Cervix	CC	cell-cell signaling by wnt	98/2311	446/18723	6.16e-09	5.58e-07	98
GO:00071598	Cervix	CC	leukocyte cell-cell adhesion	85/2311	371/18723	8.27e-09	7.07e-07	85
GO:00071626	Cervix	CC	negative regulation of cell adhesion	72/2311	303/18723	2.36e-08	1.70e-06	72
GO:00026837	Cervix	CC	negative regulation of immune system process	94/2311	434/18723	2.63e-08	1.87e-06	94
GO:00301117	Cervix	CC	regulation of Wnt signaling pathway	76/2311	328/18723	3.05e-08	2.08e-06	76
GO:19030378	Cervix	CC	regulation of leukocyte cell-cell adhesion	77/2311	336/18723	4.08e-08	2.54e-06	77
GO:190370610	Cervix	CC	regulation of hemopoiesis	80/2311	367/18723	2.14e-07	9.55e-06	80
GO:00420988	Cervix	CC	T cell proliferation	49/2311	199/18723	1.32e-06	4.49e-05	49
GO:00608287	Cervix	CC	regulation of canonical Wnt signaling pathway	58/2311	253/18723	1.83e-06	5.89e-05	58
GO:00224084	Cervix	CC	negative regulation of cell-cell adhesion	48/2311	196/18723	1.99e-06	6.18e-05	48
GO:00600707	Cervix	CC	canonical Wnt signaling pathway	66/2311	303/18723	2.47e-06	7.35e-05	66
GO:00421297	Cervix	CC	regulation of T cell proliferation	43/2311	171/18723	3.21e-06	8.77e-05	43
GO:19021056	Cervix	CC	regulation of leukocyte differentiation	61/2311	279/18723	5.16e-06	1.29e-04	61
GO:00706637	Cervix	CC	regulation of leukocyte proliferation	55/2311	245/18723	6.51e-06	1.56e-04	55
GO:19021064	Cervix	CC	negative regulation of leukocyte differentiation	29/2311	102/18723	1.02e-05	2.29e-04	29
GO:00506705	Cervix	CC	regulation of lymphocyte proliferation	51/2311	225/18723	1.05e-05	2.32e-04	51

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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

TMEM131

SNV

Missense_Mutation

novel

c.5359N>C

p.Thr1787Pro

p.T1787P

Q92545

protein_coding

tolerated_low_confidence(0.34)

benign(0)

TCGA-A2-A0D0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TMEM131

SNV

Missense_Mutation

c.3617C>G

p.Pro1206Arg

p.P1206R

Q92545

protein_coding

deleterious_low_confidence(0.02)

benign(0.069)

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TMEM131

SNV

Missense_Mutation

c.2236N>G

p.Leu746Val

p.L746V

Q92545

protein_coding

tolerated(0.15)

probably_damaging(0.991)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMEM131

SNV

Missense_Mutation

novel

c.4284N>T

p.Glu1428Asp

p.E1428D

Q92545

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.978)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMEM131

SNV

Missense_Mutation

novel

c.2614N>C

p.Ser872Pro

p.S872P

Q92545

protein_coding

tolerated(1)

benign(0.006)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMEM131

SNV

Missense_Mutation

c.1780N>C

p.Val594Leu

p.V594L

Q92545

protein_coding

tolerated(1)

benign(0)

TCGA-AN-A04D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMEM131

SNV

Missense_Mutation

c.214N>C

p.Glu72Gln

p.E72Q

Q92545

protein_coding

tolerated(0.06)

possibly_damaging(0.749)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMEM131

SNV

Missense_Mutation

novel

c.4234N>A

p.Glu1412Lys

p.E1412K

Q92545

protein_coding

deleterious_low_confidence(0.01)

benign(0.054)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

TMEM131

SNV

Missense_Mutation

c.3050G>T

p.Arg1017Ile

p.R1017I

Q92545

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-D8-A1JG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TMEM131

SNV

Missense_Mutation

rs762090529

c.2501N>A

p.Arg834Gln

p.R834Q

Q92545

protein_coding

tolerated(0.74)

benign(0)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

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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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