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: TMBIM6

Gene summary for TMBIM6

Gene summary.

Gene information	Species	Human
	Gene symbol	TMBIM6
	Gene ID	7009
	Gene name	transmembrane BAX inhibitor motif containing 6
	Gene Alias	BAXI1
	Cytomap	12q13.12
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P55061

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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
7009	TMBIM6	CCI_1	Human	Cervix	CC	2.12e-09	-8.07e-01	0.528
7009	TMBIM6	CCI_3	Human	Cervix	CC	1.03e-04	-5.74e-01	0.516
7009	TMBIM6	CCII_1	Human	Cervix	CC	5.11e-34	-1.10e+00	0.3249
7009	TMBIM6	sample3	Human	Cervix	CC	2.08e-10	2.13e-01	0.1387
7009	TMBIM6	L1	Human	Cervix	CC	3.72e-05	-2.97e-01	0.0802
7009	TMBIM6	T3	Human	Cervix	CC	5.65e-05	2.01e-01	0.1389
7009	TMBIM6	HTA11_3410_2000001011	Human	Colorectum	AD	1.23e-27	8.85e-01	0.0155
7009	TMBIM6	HTA11_2487_2000001011	Human	Colorectum	SER	2.23e-31	1.79e+00	-0.1808
7009	TMBIM6	HTA11_1938_2000001011	Human	Colorectum	AD	2.37e-37	2.06e+00	-0.0811
7009	TMBIM6	HTA11_78_2000001011	Human	Colorectum	AD	2.53e-48	2.18e+00	-0.1088
7009	TMBIM6	HTA11_347_2000001011	Human	Colorectum	AD	1.42e-83	2.53e+00	-0.1954
7009	TMBIM6	HTA11_411_2000001011	Human	Colorectum	SER	1.27e-15	2.78e+00	-0.2602
7009	TMBIM6	HTA11_2112_2000001011	Human	Colorectum	SER	4.33e-13	1.83e+00	-0.2196
7009	TMBIM6	HTA11_3361_2000001011	Human	Colorectum	AD	1.96e-17	1.16e+00	-0.1207
7009	TMBIM6	HTA11_83_2000001011	Human	Colorectum	SER	7.44e-37	2.12e+00	-0.1526
7009	TMBIM6	HTA11_696_2000001011	Human	Colorectum	AD	7.55e-51	1.72e+00	-0.1464
7009	TMBIM6	HTA11_866_2000001011	Human	Colorectum	AD	1.83e-33	1.32e+00	-0.1001
7009	TMBIM6	HTA11_1391_2000001011	Human	Colorectum	AD	2.17e-31	1.98e+00	-0.059
7009	TMBIM6	HTA11_2992_2000001011	Human	Colorectum	SER	3.03e-22	2.18e+00	-0.1706
7009	TMBIM6	HTA11_5212_2000001011	Human	Colorectum	AD	4.97e-31	2.37e+00	-0.2061

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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
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:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00434849	Breast	Precancer	regulation of RNA splicing	34/1080	148/18723	2.66e-12	4.75e-10	34
GO:00362939	Breast	Precancer	response to decreased oxygen levels	53/1080	322/18723	4.09e-12	6.84e-10	53
GO:00016669	Breast	Precancer	response to hypoxia	51/1080	307/18723	7.33e-12	1.11e-09	51
GO:00704829	Breast	Precancer	response to oxygen levels	55/1080	347/18723	7.47e-12	1.11e-09	55
GO:20012349	Breast	Precancer	negative regulation of apoptotic signaling pathway	39/1080	224/18723	5.35e-10	4.77e-08	39
GO:00362948	Breast	Precancer	cellular response to decreased oxygen levels	31/1080	161/18723	2.61e-09	2.11e-07	31
GO:00069869	Breast	Precancer	response to unfolded protein	28/1080	137/18723	3.81e-09	3.00e-07	28
GO:20012439	Breast	Precancer	negative regulation of intrinsic apoptotic signaling pathway	23/1080	98/18723	5.82e-09	4.45e-07	23
GO:00714538	Breast	Precancer	cellular response to oxygen levels	32/1080	177/18723	7.32e-09	5.52e-07	32
GO:00714565	Breast	Precancer	cellular response to hypoxia	29/1080	151/18723	8.98e-09	6.50e-07	29
GO:00359669	Breast	Precancer	response to topologically incorrect protein	29/1080	159/18723	3.00e-08	1.89e-06	29
GO:00513468	Breast	Precancer	negative regulation of hydrolase activity	50/1080	379/18723	3.85e-08	2.34e-06	50
GO:00349769	Breast	Precancer	response to endoplasmic reticulum stress	38/1080	256/18723	7.89e-08	4.60e-06	38
GO:00346209	Breast	Precancer	cellular response to unfolded protein	21/1080	96/18723	9.80e-08	5.46e-06	21
GO:00359679	Breast	Precancer	cellular response to topologically incorrect protein	22/1080	116/18723	6.84e-07	2.80e-05	22
GO:00510989	Breast	Precancer	regulation of binding	44/1080	363/18723	2.59e-06	8.65e-05	44

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513018	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0513019	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0513024	Breast	IDC	Pathogenic Escherichia coli infection	42/867	197/8465	2.66e-06	3.92e-05	2.94e-05	42
hsa0513034	Breast	IDC	Pathogenic Escherichia coli infection	42/867	197/8465	2.66e-06	3.92e-05	2.94e-05	42
hsa0513043	Breast	DCIS	Pathogenic Escherichia coli infection	42/846	197/8465	1.40e-06	2.15e-05	1.59e-05	42
hsa0513053	Breast	DCIS	Pathogenic Escherichia coli infection	42/846	197/8465	1.40e-06	2.15e-05	1.59e-05	42
hsa0513020	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0513044	Cervix	N_HPV	Pathogenic Escherichia coli infection	25/349	197/8465	4.71e-07	8.00e-06	6.25e-06	25
hsa0513054	Cervix	N_HPV	Pathogenic Escherichia coli infection	25/349	197/8465	4.71e-07	8.00e-06	6.25e-06	25
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051302	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60
hsa051303	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60
hsa051304	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa051305	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa051306	Colorectum	MSI-H	Pathogenic Escherichia coli infection	31/797	197/8465	2.90e-03	2.93e-02	2.46e-02	31
hsa051307	Colorectum	MSI-H	Pathogenic Escherichia coli infection	31/797	197/8465	2.90e-03	2.93e-02	2.46e-02	31
hsa051308	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62
hsa051309	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62

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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

TMBIM6

SNV

Missense_Mutation

novel

c.104G>T

p.Arg35Leu

p.R35L

P55061

protein_coding

tolerated_low_confidence(0.08)

benign(0.001)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

TMBIM6

deletion

Frame_Shift_Del

novel

c.702delN

p.Gly235AspfsTer36

p.G235Dfs*36

P55061

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TMBIM6

SNV

Missense_Mutation

c.35N>T

p.Gln12Leu

p.Q12L

P55061

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-AZ-5407-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

TMBIM6

SNV

Missense_Mutation

c.728N>A

p.Val243Asp

p.V243D

P55061

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-D5-6928-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TMBIM6

SNV

Missense_Mutation

c.185T>C

p.Phe62Ser

p.F62S

P55061

protein_coding

deleterious(0)

possibly_damaging(0.677)

TCGA-D5-7000-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TMBIM6

SNV

Missense_Mutation

novel

c.675N>G

p.Ile225Met

p.I225M

P55061

protein_coding

tolerated(0.23)

benign(0.012)

TCGA-AJ-A3EL-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMBIM6

SNV

Missense_Mutation

novel

c.497N>A

p.Ala166Asp

p.A166D

P55061

protein_coding

tolerated(0.53)

benign(0.007)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

TMBIM6

SNV

Missense_Mutation

c.521N>T

p.Thr174Ile

p.T174I

P55061

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMBIM6

insertion

Frame_Shift_Ins

novel

c.731_732insA

p.Asp246Ter

p.D246*

P55061

protein_coding

TCGA-A5-A0R9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMBIM6

insertion

Nonsense_Mutation

novel

c.732_733insGAAGGATAATGGGAAGGC

p.Leu244_Phe245insGluGlyTerTrpGluGly

p.L244_F245insEG*WEG

P55061

protein_coding

TCGA-A5-A0R9-01

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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