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: CHCHD3

Gene summary for CHCHD3

Gene summary.

Gene information	Species	Human
	Gene symbol	CHCHD3
	Gene ID	54927
	Gene name	coiled-coil-helix-coiled-coil-helix domain containing 3
	Gene Alias	MICOS19
	Cytomap	7q32.3-q33
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	C9JRZ6

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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
54927	CHCHD3	CCI_2	Human	Cervix	CC	1.30e-16	1.49e+00	0.5249
54927	CHCHD3	CCI_3	Human	Cervix	CC	1.93e-11	8.27e-01	0.516
54927	CHCHD3	HTA11_2487_2000001011	Human	Colorectum	SER	3.03e-04	6.21e-01	-0.1808
54927	CHCHD3	HTA11_2951_2000001011	Human	Colorectum	AD	4.75e-15	1.14e+00	0.0216
54927	CHCHD3	HTA11_1938_2000001011	Human	Colorectum	AD	2.17e-08	9.62e-01	-0.0811
54927	CHCHD3	HTA11_78_2000001011	Human	Colorectum	AD	3.36e-08	9.28e-01	-0.1088
54927	CHCHD3	HTA11_347_2000001011	Human	Colorectum	AD	6.53e-24	1.14e+00	-0.1954
54927	CHCHD3	HTA11_411_2000001011	Human	Colorectum	SER	7.13e-09	9.83e-01	-0.2602
54927	CHCHD3	HTA11_2112_2000001011	Human	Colorectum	SER	2.99e-07	1.31e+00	-0.2196
54927	CHCHD3	HTA11_3361_2000001011	Human	Colorectum	AD	8.77e-09	9.69e-01	-0.1207
54927	CHCHD3	HTA11_83_2000001011	Human	Colorectum	SER	2.81e-17	9.99e-01	-0.1526
54927	CHCHD3	HTA11_696_2000001011	Human	Colorectum	AD	2.76e-37	1.54e+00	-0.1464
54927	CHCHD3	HTA11_866_2000001011	Human	Colorectum	AD	1.88e-11	9.60e-01	-0.1001
54927	CHCHD3	HTA11_1391_2000001011	Human	Colorectum	AD	2.75e-24	1.65e+00	-0.059
54927	CHCHD3	HTA11_2992_2000001011	Human	Colorectum	SER	6.13e-21	1.33e+00	-0.1706
54927	CHCHD3	HTA11_5212_2000001011	Human	Colorectum	AD	5.81e-03	3.44e-01	-0.2061
54927	CHCHD3	HTA11_5216_2000001011	Human	Colorectum	SER	7.28e-17	1.21e+00	-0.1462
54927	CHCHD3	HTA11_546_2000001011	Human	Colorectum	AD	2.10e-15	1.05e+00	-0.0842
54927	CHCHD3	HTA11_9341_2000001011	Human	Colorectum	SER	2.83e-25	1.67e+00	-0.00410000000000005
54927	CHCHD3	HTA11_7862_2000001011	Human	Colorectum	AD	5.27e-23	1.10e+00	-0.0179

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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
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
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:00070067	Cervix	CC	mitochondrial membrane organization	28/2311	116/18723	3.28e-04	3.47e-03	28
GO:00070074	Cervix	CC	inner mitochondrial membrane organization	11/2311	38/18723	4.94e-03	2.95e-02	11
GO:0007006	Colorectum	AD	mitochondrial membrane organization	48/3918	116/18723	4.53e-07	1.72e-05	48
GO:0007007	Colorectum	AD	inner mitochondrial membrane organization	18/3918	38/18723	2.45e-04	3.09e-03	18
GO:0048284	Colorectum	AD	organelle fusion	42/3918	141/18723	8.04e-03	4.73e-02	42
GO:00070061	Colorectum	SER	mitochondrial membrane organization	38/2897	116/18723	2.66e-06	1.10e-04	38
GO:00070071	Colorectum	SER	inner mitochondrial membrane organization	14/2897	38/18723	1.06e-03	1.23e-02	14
GO:00070062	Colorectum	MSS	mitochondrial membrane organization	42/3467	116/18723	4.99e-06	1.38e-04	42
GO:00482841	Colorectum	MSS	organelle fusion	39/3467	141/18723	4.91e-03	3.42e-02	39
GO:00070072	Colorectum	MSS	inner mitochondrial membrane organization	14/3467	38/18723	6.00e-03	4.03e-02	14
GO:00070063	Colorectum	MSI-H	mitochondrial membrane organization	18/1319	116/18723	1.24e-03	2.00e-02	18
GO:000700618	Esophagus	HGIN	mitochondrial membrane organization	37/2587	116/18723	4.61e-07	2.07e-05	37
GO:00070076	Esophagus	HGIN	inner mitochondrial membrane organization	16/2587	38/18723	1.82e-05	4.93e-04	16
GO:000700619	Esophagus	ESCC	mitochondrial membrane organization	93/8552	116/18723	2.16e-14	1.11e-12	93
GO:00482844	Esophagus	ESCC	organelle fusion	94/8552	141/18723	3.72e-07	5.16e-06	94
GO:000700713	Esophagus	ESCC	inner mitochondrial membrane organization	31/8552	38/18723	5.93e-06	6.10e-05	31
GO:00080532	Esophagus	ESCC	mitochondrial fusion	20/8552	27/18723	2.61e-03	1.11e-02	20
GO:00424072	Esophagus	ESCC	cristae formation	13/8552	16/18723	4.05e-03	1.62e-02	13
GO:00070065	Liver	Cirrhotic	mitochondrial membrane organization	57/4634	116/18723	1.13e-08	4.29e-07	57
GO:00070073	Liver	Cirrhotic	inner mitochondrial membrane organization	19/4634	38/18723	6.75e-04	5.06e-03	19

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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

CHCHD3

SNV

Missense_Mutation

c.586N>C

p.Glu196Gln

p.E196Q

Q9NX63

protein_coding

tolerated(0.52)

benign(0.015)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

CHCHD3

SNV

Missense_Mutation

c.670N>C

p.Glu224Gln

p.E224Q

Q9NX63

protein_coding

tolerated(0.66)

benign(0)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CHCHD3

SNV

Missense_Mutation

c.670N>C

p.Glu224Gln

p.E224Q

Q9NX63

protein_coding

tolerated(0.66)

benign(0)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

CHCHD3

SNV

Missense_Mutation

novel

c.211G>A

p.Ala71Thr

p.A71T

Q9NX63

protein_coding

deleterious(0.05)

probably_damaging(0.984)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

CHCHD3

SNV

Missense_Mutation

rs747561997

c.583N>T

p.Arg195Cys

p.R195C

Q9NX63

protein_coding

deleterious(0.05)

benign(0.003)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

CHCHD3

SNV

Missense_Mutation

novel

c.128G>A

p.Gly43Asp

p.G43D

Q9NX63

protein_coding

tolerated(0.16)

possibly_damaging(0.53)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CHCHD3

SNV

Missense_Mutation

novel

c.453G>T

p.Arg151Ser

p.R151S

Q9NX63

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-B5-A5OC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

cisplatin

CHCHD3

SNV

Missense_Mutation

rs145165887

c.584N>A

p.Arg195His

p.R195H

Q9NX63

protein_coding

deleterious(0.02)

benign(0.323)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CHCHD3

SNV

Missense_Mutation

novel

c.10N>G

p.Thr4Ala

p.T4A

Q9NX63

protein_coding

tolerated(0.3)

benign(0)

TCGA-D1-A167-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CHCHD3

SNV

Missense_Mutation

c.653N>T

p.Ala218Val

p.A218V

Q9NX63

protein_coding

deleterious(0)

probably_damaging(0.922)

TCGA-D1-A16X-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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