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: CHD6

Gene summary for CHD6

Gene summary.

Gene information	Species	Human
	Gene symbol	CHD6
	Gene ID	84181
	Gene name	chromodomain helicase DNA binding protein 6
	Gene Alias	CHD-6
	Cytomap	20q12
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q8TD26

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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
84181	CHD6	CCI_2	Human	Cervix	CC	9.21e-06	7.69e-01	0.5249
84181	CHD6	CCI_3	Human	Cervix	CC	6.08e-09	8.50e-01	0.516
84181	CHD6	HTA11_3410_2000001011	Human	Colorectum	AD	2.16e-20	-5.75e-01	0.0155
84181	CHD6	HTA11_2487_2000001011	Human	Colorectum	SER	9.33e-09	-5.94e-01	-0.1808
84181	CHD6	HTA11_1938_2000001011	Human	Colorectum	AD	2.10e-05	-4.86e-01	-0.0811
84181	CHD6	HTA11_78_2000001011	Human	Colorectum	AD	3.23e-04	-4.09e-01	-0.1088
84181	CHD6	HTA11_2112_2000001011	Human	Colorectum	SER	2.13e-02	-7.17e-01	-0.2196
84181	CHD6	HTA11_3361_2000001011	Human	Colorectum	AD	5.64e-07	-5.59e-01	-0.1207
84181	CHD6	HTA11_83_2000001011	Human	Colorectum	SER	9.12e-07	-5.95e-01	-0.1526
84181	CHD6	HTA11_696_2000001011	Human	Colorectum	AD	4.00e-06	-4.11e-01	-0.1464
84181	CHD6	HTA11_866_2000001011	Human	Colorectum	AD	3.77e-07	-4.39e-01	-0.1001
84181	CHD6	HTA11_1391_2000001011	Human	Colorectum	AD	5.35e-05	-4.01e-01	-0.059
84181	CHD6	HTA11_5212_2000001011	Human	Colorectum	AD	2.20e-04	-6.79e-01	-0.2061
84181	CHD6	HTA11_7862_2000001011	Human	Colorectum	AD	1.36e-02	-5.56e-01	-0.0179
84181	CHD6	HTA11_866_3004761011	Human	Colorectum	AD	3.51e-05	-4.02e-01	0.096
84181	CHD6	HTA11_8622_2000001021	Human	Colorectum	SER	1.85e-03	-5.00e-01	0.0528
84181	CHD6	HTA11_10623_2000001011	Human	Colorectum	AD	2.61e-03	-5.27e-01	-0.0177
84181	CHD6	HTA11_10711_2000001011	Human	Colorectum	AD	7.12e-07	-3.90e-01	0.0338
84181	CHD6	HTA11_7696_3000711011	Human	Colorectum	AD	3.75e-14	-5.08e-01	0.0674
84181	CHD6	HTA11_99999970781_79442	Human	Colorectum	MSS	1.02e-05	-3.59e-01	0.294

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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
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:000697910	Cervix	CC	response to oxidative stress	102/2311	446/18723	2.99e-10	4.36e-08	102
GO:004361810	Cervix	CC	regulation of transcription from RNA polymerase II promoter in response to stress	21/2311	47/18723	3.85e-08	2.53e-06	21
GO:004362010	Cervix	CC	regulation of DNA-templated transcription in response to stress	22/2311	53/18723	9.29e-08	5.19e-06	22
GO:006219710	Cervix	CC	cellular response to chemical stress	76/2311	337/18723	1.01e-07	5.25e-06	76
GO:003459910	Cervix	CC	cellular response to oxidative stress	63/2311	288/18723	3.58e-06	9.50e-05	63
GO:00063257	Cervix	CC	chromatin organization	78/2311	409/18723	5.40e-05	8.02e-04	78
GO:00360038	Cervix	CC	positive regulation of transcription from RNA polymerase II promoter in response to stress	10/2311	24/18723	3.05e-04	3.26e-03	10
GO:00323923	Cervix	CC	DNA geometric change	21/2311	90/18723	2.71e-03	1.85e-02	21
GO:0006979	Colorectum	AD	response to oxidative stress	145/3918	446/18723	5.16e-09	3.23e-07	145
GO:0062197	Colorectum	AD	cellular response to chemical stress	109/3918	337/18723	5.33e-07	1.95e-05	109
GO:0034599	Colorectum	AD	cellular response to oxidative stress	94/3918	288/18723	2.03e-06	6.02e-05	94
GO:0006325	Colorectum	AD	chromatin organization	119/3918	409/18723	4.85e-05	8.33e-04	119
GO:0043620	Colorectum	AD	regulation of DNA-templated transcription in response to stress	23/3918	53/18723	1.86e-04	2.49e-03	23
GO:0036003	Colorectum	AD	positive regulation of transcription from RNA polymerase II promoter in response to stress	13/3918	24/18723	3.45e-04	4.03e-03	13
GO:0043618	Colorectum	AD	regulation of transcription from RNA polymerase II promoter in response to stress	20/3918	47/18723	6.54e-04	6.75e-03	20
GO:0032392	Colorectum	AD	DNA geometric change	31/3918	90/18723	2.02e-03	1.63e-02	31
GO:0043619	Colorectum	AD	regulation of transcription from RNA polymerase II promoter in response to oxidative stress	7/3918	11/18723	2.59e-03	1.96e-02	7
GO:00069791	Colorectum	SER	response to oxidative stress	114/2897	446/18723	1.75e-08	1.28e-06	114
GO:00621971	Colorectum	SER	cellular response to chemical stress	87/2897	337/18723	5.33e-07	2.59e-05	87
GO:00345991	Colorectum	SER	cellular response to oxidative stress	73/2897	288/18723	8.52e-06	2.86e-04	73

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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

CHD6

SNV

Missense_Mutation

c.8011N>G

p.Pro2671Ala

p.P2671A

Q8TD26

protein_coding

tolerated_low_confidence(0.15)

benign(0.039)

TCGA-A1-A0SO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

CHD6

SNV

Missense_Mutation

novel

c.7042C>A

p.Gln2348Lys

p.Q2348K

Q8TD26

protein_coding

tolerated(0.18)

benign(0.014)

TCGA-A2-A04X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CHD6

SNV

Missense_Mutation

c.4811N>G

p.Pro1604Arg

p.P1604R

Q8TD26

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-A7-A0CD-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CHD6

SNV

Missense_Mutation

c.402G>T

p.Lys134Asn

p.K134N

Q8TD26

protein_coding

tolerated(0.31)

possibly_damaging(0.462)

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CHD6

SNV

Missense_Mutation

novel

c.7034N>G

p.Ala2345Gly

p.A2345G

Q8TD26

protein_coding

tolerated(0.17)

benign(0.049)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CHD6

SNV

Missense_Mutation

c.1159A>G

p.Lys387Glu

p.K387E

Q8TD26

protein_coding

tolerated(0.56)

benign(0.055)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CHD6

SNV

Missense_Mutation

novel

c.6412N>C

p.Thr2138Pro

p.T2138P

Q8TD26

protein_coding

tolerated(0.13)

benign(0.017)

TCGA-AR-A1AP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CHD6

SNV

Missense_Mutation

novel

c.5231A>C

p.Asn1744Thr

p.N1744T

Q8TD26

protein_coding

deleterious_low_confidence(0.01)

benign(0.01)

TCGA-BH-A0BG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CHD6

SNV

Missense_Mutation

novel

c.6412N>C

p.Thr2138Pro

p.T2138P

Q8TD26

protein_coding

tolerated(0.13)

benign(0.017)

TCGA-BH-A0BR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CHD6

SNV

Missense_Mutation

c.11N>C

p.Lys4Thr

p.K4T

Q8TD26

protein_coding

deleterious_low_confidence(0)

benign(0.247)

TCGA-BH-A0BR-01

Breast

breast invasive 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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