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: TIMM17B

Gene summary for TIMM17B

Gene summary.

Gene information	Species	Human
	Gene symbol	TIMM17B
	Gene ID	10245
	Gene name	translocase of inner mitochondrial membrane 17B
	Gene Alias	DXS9822
	Cytomap	Xp11.23
	Gene Type	protein-coding
	GO ID	GO:0006605
	UniProtAcc	O60830

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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
10245	TIMM17B	P38T-E	Human	Esophagus	ESCC	9.77e-15	3.69e-01	0.127
10245	TIMM17B	P39T-E	Human	Esophagus	ESCC	1.23e-21	5.96e-01	0.0894
10245	TIMM17B	P40T-E	Human	Esophagus	ESCC	1.35e-24	8.25e-01	0.109
10245	TIMM17B	P42T-E	Human	Esophagus	ESCC	3.77e-23	5.62e-01	0.1175
10245	TIMM17B	P44T-E	Human	Esophagus	ESCC	1.34e-17	5.36e-01	0.1096
10245	TIMM17B	P47T-E	Human	Esophagus	ESCC	2.85e-47	1.04e+00	0.1067
10245	TIMM17B	P48T-E	Human	Esophagus	ESCC	7.40e-32	5.97e-01	0.0959
10245	TIMM17B	P49T-E	Human	Esophagus	ESCC	2.60e-12	1.28e+00	0.1768
10245	TIMM17B	P52T-E	Human	Esophagus	ESCC	2.68e-44	1.19e+00	0.1555
10245	TIMM17B	P54T-E	Human	Esophagus	ESCC	2.11e-20	6.24e-01	0.0975
10245	TIMM17B	P56T-E	Human	Esophagus	ESCC	5.01e-09	1.45e+00	0.1613
10245	TIMM17B	P57T-E	Human	Esophagus	ESCC	4.64e-23	5.35e-01	0.0926
10245	TIMM17B	P61T-E	Human	Esophagus	ESCC	2.43e-29	9.63e-01	0.099
10245	TIMM17B	P62T-E	Human	Esophagus	ESCC	9.55e-53	1.12e+00	0.1302
10245	TIMM17B	P65T-E	Human	Esophagus	ESCC	5.62e-23	5.11e-01	0.0978
10245	TIMM17B	P74T-E	Human	Esophagus	ESCC	5.33e-38	1.03e+00	0.1479
10245	TIMM17B	P75T-E	Human	Esophagus	ESCC	2.26e-54	1.15e+00	0.1125
10245	TIMM17B	P76T-E	Human	Esophagus	ESCC	5.98e-47	1.02e+00	0.1207
10245	TIMM17B	P79T-E	Human	Esophagus	ESCC	4.81e-90	2.07e+00	0.1154
10245	TIMM17B	P80T-E	Human	Esophagus	ESCC	1.78e-61	2.00e+00	0.155

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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

∗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:0006839	Colorectum	AD	mitochondrial transport	102/3918	254/18723	1.87e-12	3.08e-10	102
GO:0072594	Colorectum	AD	establishment of protein localization to organelle	148/3918	422/18723	7.95e-12	1.04e-09	148
GO:1990542	Colorectum	AD	mitochondrial transmembrane transport	47/3918	102/18723	1.09e-08	6.52e-07	47
GO:0006605	Colorectum	AD	protein targeting	105/3918	314/18723	1.39e-07	6.44e-06	105
GO:0070585	Colorectum	AD	protein localization to mitochondrion	51/3918	125/18723	3.40e-07	1.33e-05	51
GO:0072655	Colorectum	AD	establishment of protein localization to mitochondrion	47/3918	120/18723	3.76e-06	1.04e-04	47
GO:0017038	Colorectum	AD	protein import	67/3918	206/18723	6.34e-05	1.05e-03	67
GO:0006626	Colorectum	AD	protein targeting to mitochondrion	37/3918	100/18723	1.58e-04	2.20e-03	37
GO:0071806	Colorectum	AD	protein transmembrane transport	21/3918	59/18723	6.58e-03	4.08e-02	21
GO:00068391	Colorectum	SER	mitochondrial transport	87/2897	254/18723	7.91e-14	3.03e-11	87
GO:19905421	Colorectum	SER	mitochondrial transmembrane transport	42/2897	102/18723	3.65e-10	4.77e-08	42
GO:00725941	Colorectum	SER	establishment of protein localization to organelle	111/2897	422/18723	4.98e-09	4.49e-07	111
GO:00705851	Colorectum	SER	protein localization to mitochondrion	42/2897	125/18723	3.75e-07	1.98e-05	42
GO:00726551	Colorectum	SER	establishment of protein localization to mitochondrion	38/2897	120/18723	6.60e-06	2.33e-04	38
GO:00066051	Colorectum	SER	protein targeting	76/2897	314/18723	3.19e-05	8.47e-04	76
GO:00066261	Colorectum	SER	protein targeting to mitochondrion	31/2897	100/18723	7.09e-05	1.61e-03	31
GO:00170381	Colorectum	SER	protein import	49/2897	206/18723	1.12e-03	1.29e-02	49
GO:00718061	Colorectum	SER	protein transmembrane transport	17/2897	59/18723	6.64e-03	4.69e-02	17
GO:00725942	Colorectum	MSS	establishment of protein localization to organelle	139/3467	422/18723	5.75e-13	1.12e-10	139
GO:00068392	Colorectum	MSS	mitochondrial transport	93/3467	254/18723	6.14e-12	9.82e-10	93

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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

TIMM17B

SNV

Missense_Mutation

c.542N>C

p.Ile181Thr

p.I181T

O60830

protein_coding

deleterious(0)

probably_damaging(0.969)

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

TIMM17B

insertion

Frame_Shift_Ins

novel

c.225_226insTGTAAACATTTGTCAACTCCCCATAAAGATGAAGGGAATGTTG

p.Thr76CysfsTer40

p.T76Cfs*40

O60830

protein_coding

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TIMM17B

insertion

In_Frame_Ins

novel

c.89_97dupTCTTCCAGG

p.Val30_Gln32dup

p.V30_Q32dup

O60830

protein_coding

TCGA-UL-AAZ6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

herceptin

TIMM17B

SNV

Missense_Mutation

c.466N>T

p.Arg156Cys

p.R156C

O60830

protein_coding

deleterious(0.02)

benign(0.233)

TCGA-CM-6162-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

oxaliplatin

TIMM17B

SNV

Missense_Mutation

novel

c.13G>A

p.Ala5Thr

p.A5T

O60830

protein_coding

tolerated(0.39)

possibly_damaging(0.578)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

TIMM17B

SNV

Missense_Mutation

novel

c.112N>T

p.Arg38Cys

p.R38C

O60830

protein_coding

deleterious(0)

benign(0.104)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TIMM17B

SNV

Missense_Mutation

novel

c.58G>A

p.Ala20Thr

p.A20T

O60830

protein_coding

deleterious(0)

probably_damaging(0.947)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TIMM17B

SNV

Missense_Mutation

novel

c.586C>A

p.Pro196Thr

p.P196T

O60830

protein_coding

tolerated(0.06)

possibly_damaging(0.844)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TIMM17B

SNV

Missense_Mutation

novel

c.113N>A

p.Arg38His

p.R38H

O60830

protein_coding

deleterious(0.01)

benign(0.33)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TIMM17B

SNV

Missense_Mutation

novel

c.400N>T

p.Arg134Trp

p.R134W

O60830

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

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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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