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	GSM4909280	Human	Breast	Precancer	1.29e-07	-8.90e-01	0.0305
7009	TMBIM6	GSM4909281	Human	Breast	IDC	1.53e-06	-2.34e-01	0.21
7009	TMBIM6	GSM4909282	Human	Breast	IDC	9.95e-20	-4.93e-01	-0.0288
7009	TMBIM6	GSM4909285	Human	Breast	IDC	3.54e-06	-1.27e-01	0.21
7009	TMBIM6	GSM4909286	Human	Breast	IDC	5.55e-33	-5.97e-01	0.1081
7009	TMBIM6	GSM4909287	Human	Breast	IDC	5.22e-19	-6.25e-01	0.2057
7009	TMBIM6	GSM4909288	Human	Breast	IDC	1.89e-03	-4.27e-01	0.0988
7009	TMBIM6	GSM4909290	Human	Breast	IDC	5.50e-04	-3.51e-01	0.2096
7009	TMBIM6	GSM4909293	Human	Breast	IDC	4.77e-05	-1.58e-01	0.1581
7009	TMBIM6	GSM4909294	Human	Breast	IDC	3.54e-20	-5.40e-01	0.2022
7009	TMBIM6	GSM4909295	Human	Breast	IDC	1.88e-05	-4.91e-01	0.0898
7009	TMBIM6	GSM4909296	Human	Breast	IDC	1.65e-12	-3.53e-01	0.1524
7009	TMBIM6	GSM4909297	Human	Breast	IDC	3.15e-21	-5.33e-01	0.1517
7009	TMBIM6	GSM4909298	Human	Breast	IDC	6.27e-03	-6.25e-02	0.1551
7009	TMBIM6	GSM4909299	Human	Breast	IDC	2.09e-02	-2.49e-01	0.035
7009	TMBIM6	GSM4909305	Human	Breast	IDC	3.74e-02	-2.64e-01	0.0436
7009	TMBIM6	GSM4909307	Human	Breast	IDC	5.44e-04	-3.25e-01	0.1569
7009	TMBIM6	GSM4909308	Human	Breast	IDC	1.71e-02	-1.51e-01	0.158
7009	TMBIM6	GSM4909309	Human	Breast	IDC	1.07e-02	-2.46e-01	0.0483
7009	TMBIM6	GSM4909311	Human	Breast	IDC	1.02e-44	-5.39e-01	0.1534

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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:190589728	Thyroid	ATC	regulation of response to endoplasmic reticulum stress	54/6293	82/18723	2.34e-09	5.58e-08	54
GO:0070059113	Thyroid	ATC	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	43/6293	63/18723	1.98e-08	3.90e-07	43
GO:007145325	Thyroid	ATC	cellular response to oxygen levels	94/6293	177/18723	6.62e-08	1.17e-06	94
GO:190357327	Thyroid	ATC	negative regulation of response to endoplasmic reticulum stress	32/6293	44/18723	1.28e-07	2.12e-06	32
GO:005110027	Thyroid	ATC	negative regulation of binding	86/6293	162/18723	2.41e-07	3.73e-06	86
GO:003311935	Thyroid	ATC	negative regulation of RNA splicing	21/6293	25/18723	3.02e-07	4.52e-06	21
GO:003629425	Thyroid	ATC	cellular response to decreased oxygen levels	85/6293	161/18723	3.86e-07	5.65e-06	85
GO:0043620210	Thyroid	ATC	regulation of DNA-templated transcription in response to stress	35/6293	53/18723	1.39e-06	1.74e-05	35
GO:004361829	Thyroid	ATC	regulation of transcription from RNA polymerase II promoter in response to stress	32/6293	47/18723	1.42e-06	1.77e-05	32
GO:007145624	Thyroid	ATC	cellular response to hypoxia	78/6293	151/18723	3.44e-06	3.86e-05	78
GO:003246925	Thyroid	ATC	endoplasmic reticulum calcium ion homeostasis	19/6293	25/18723	1.77e-05	1.62e-04	19
GO:000110124	Thyroid	ATC	response to acid chemical	69/6293	135/18723	1.95e-05	1.76e-04	69
GO:1902236112	Thyroid	ATC	negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	16/6293	20/18723	2.79e-05	2.36e-04	16
GO:003209119	Thyroid	ATC	negative regulation of protein binding	51/6293	94/18723	2.97e-05	2.48e-04	51
GO:003206923	Thyroid	ATC	regulation of nuclease activity	17/6293	22/18723	3.47e-05	2.84e-04	17
GO:190223518	Thyroid	ATC	regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	22/6293	32/18723	5.14e-05	3.99e-04	22
GO:004320022	Thyroid	ATC	response to amino acid	58/6293	116/18723	1.88e-04	1.26e-03	58
GO:005134629	Thyroid	ATC	negative regulation of hydrolase activity	155/6293	379/18723	1.64e-03	8.23e-03	155
GO:009720132	Thyroid	ATC	negative regulation of transcription from RNA polymerase II promoter in response to stress	9/6293	12/18723	4.10e-03	1.75e-02	9
GO:005105114	Thyroid	ATC	negative regulation of transport	183/6293	470/18723	8.12e-03	3.13e-02	183

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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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