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: DNAJC1

Gene summary for DNAJC1

Gene summary.

Gene information	Species	Human
	Gene symbol	DNAJC1
	Gene ID	64215
	Gene name	DnaJ heat shock protein family (Hsp40) member C1
	Gene Alias	DNAJL1
	Cytomap	10p12.31
	Gene Type	protein-coding
	GO ID	GO:0006412
	UniProtAcc	Q96KC8

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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
64215	DNAJC1	GSM4909282	Human	Breast	IDC	3.58e-02	9.73e-02	-0.0288
64215	DNAJC1	GSM4909285	Human	Breast	IDC	5.36e-06	2.19e-01	0.21
64215	DNAJC1	GSM4909291	Human	Breast	IDC	1.13e-04	3.32e-01	0.1753
64215	DNAJC1	GSM4909296	Human	Breast	IDC	3.92e-08	-1.83e-02	0.1524
64215	DNAJC1	GSM4909297	Human	Breast	IDC	2.97e-07	-8.78e-02	0.1517
64215	DNAJC1	GSM4909301	Human	Breast	IDC	4.99e-02	1.62e-01	0.1577
64215	DNAJC1	GSM4909302	Human	Breast	IDC	6.38e-14	4.52e-01	0.1545
64215	DNAJC1	GSM4909307	Human	Breast	IDC	7.94e-24	5.90e-01	0.1569
64215	DNAJC1	GSM4909308	Human	Breast	IDC	2.31e-26	5.96e-01	0.158
64215	DNAJC1	GSM4909311	Human	Breast	IDC	2.28e-17	-1.26e-01	0.1534
64215	DNAJC1	GSM4909312	Human	Breast	IDC	1.55e-14	2.77e-01	0.1552
64215	DNAJC1	GSM4909319	Human	Breast	IDC	3.31e-35	1.05e-01	0.1563
64215	DNAJC1	GSM4909321	Human	Breast	IDC	4.99e-12	1.03e-01	0.1559
64215	DNAJC1	M5	Human	Breast	IDC	1.67e-07	6.64e-01	0.1598
64215	DNAJC1	NCCBC14	Human	Breast	DCIS	3.62e-03	-2.37e-01	0.2021
64215	DNAJC1	NCCBC5	Human	Breast	DCIS	7.62e-05	-8.00e-02	0.2046
64215	DNAJC1	P1	Human	Breast	IDC	1.45e-10	-2.15e-01	0.1527
64215	DNAJC1	P2	Human	Breast	IDC	8.37e-03	-1.20e-01	0.21
64215	DNAJC1	DCIS2	Human	Breast	DCIS	5.71e-47	1.51e-01	0.0085
64215	DNAJC1	HTA11_3410_2000001011	Human	Colorectum	AD	1.85e-10	-3.62e-01	0.0155

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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
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
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:006500213	Oral cavity	LP	intracellular protein transmembrane transport	31/4623	51/18723	4.70e-08	1.64e-06	31
GO:0031667110	Oral cavity	LP	response to nutrient levels	165/4623	474/18723	3.87e-07	1.12e-05	165
GO:004474311	Oral cavity	LP	protein transmembrane import into intracellular organelle	22/4623	36/18723	3.76e-06	7.90e-05	22
GO:0031668110	Oral cavity	LP	cellular response to extracellular stimulus	91/4623	246/18723	1.07e-05	1.94e-04	91
GO:0045861110	Oral cavity	LP	negative regulation of proteolysis	122/4623	351/18723	1.32e-05	2.34e-04	122
GO:003166919	Oral cavity	LP	cellular response to nutrient levels	79/4623	215/18723	5.16e-05	7.21e-04	79
GO:00301502	Oral cavity	LP	protein import into mitochondrial matrix	13/4623	20/18723	1.59e-04	1.79e-03	13
GO:000926718	Oral cavity	LP	cellular response to starvation	59/4623	156/18723	1.78e-04	1.99e-03	59
GO:004345714	Oral cavity	LP	regulation of cellular respiration	24/4623	49/18723	2.00e-04	2.18e-03	24
GO:190371515	Oral cavity	LP	regulation of aerobic respiration	18/4623	33/18723	2.26e-04	2.41e-03	18
GO:004259417	Oral cavity	LP	response to starvation	71/4623	197/18723	2.36e-04	2.52e-03	71
GO:004346717	Oral cavity	LP	regulation of generation of precursor metabolites and energy	50/4623	130/18723	3.37e-04	3.37e-03	50
GO:003133319	Oral cavity	LP	negative regulation of protein-containing complex assembly	52/4623	141/18723	8.28e-04	7.24e-03	52
GO:199054219	Oral cavity	LP	mitochondrial transmembrane transport	37/4623	102/18723	5.93e-03	3.53e-02	37
GO:006145818	Oral cavity	LP	reproductive system development	128/4623	427/18723	6.91e-03	3.96e-02	128
GO:004860817	Oral cavity	LP	reproductive structure development	127/4623	424/18723	7.31e-03	4.08e-02	127
GO:003238622	Oral cavity	EOLP	regulation of intracellular transport	91/2218	337/18723	1.51e-14	6.47e-12	91
GO:000641726	Oral cavity	EOLP	regulation of translation	108/2218	468/18723	4.04e-12	7.34e-10	108
GO:000645725	Oral cavity	EOLP	protein folding	59/2218	212/18723	1.76e-10	1.79e-08	59
GO:001648223	Oral cavity	EOLP	cytosolic transport	44/2218	168/18723	2.40e-07	7.45e-06	44

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041418	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa041419	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414116	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37
hsa0414117	Lung	IAC	Protein processing in endoplasmic reticulum	37/1053	174/8465	6.53e-04	5.73e-03	3.81e-03	37

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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

DNAJC1

SNV

Missense_Mutation

c.869N>T

p.Pro290Leu

p.P290L

Q96KC8

protein_coding

deleterious(0.01)

benign(0.005)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DNAJC1

SNV

Missense_Mutation

c.1644N>C

p.Lys548Asn

p.K548N

Q96KC8

protein_coding

deleterious(0)

possibly_damaging(0.563)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

DNAJC1

insertion

Frame_Shift_Ins

novel

c.1285_1286insTGATGGGGAAAGAGGCCTCTGCACAGGTGTTAGAATCC

p.Asp429ValfsTer58

p.D429Vfs*58

Q96KC8

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

DNAJC1

SNV

Missense_Mutation

rs781526289

c.1333N>T

p.Arg445Trp

p.R445W

Q96KC8

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-C5-A7CO-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

DNAJC1

SNV

Missense_Mutation

c.1252G>C

p.Glu418Gln

p.E418Q

Q96KC8

protein_coding

tolerated(0.25)

benign(0.005)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

DNAJC1

SNV

Missense_Mutation

c.1180N>C

p.Val394Leu

p.V394L

Q96KC8

protein_coding

tolerated(0.13)

benign(0.001)

TCGA-JW-A5VK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DNAJC1

SNV

Missense_Mutation

c.1466N>C

p.Arg489Thr

p.R489T

Q96KC8

protein_coding

tolerated(0.17)

benign(0.024)

TCGA-Q1-A73P-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DNAJC1

SNV

Missense_Mutation

c.1225N>A

p.Asp409Asn

p.D409N

Q96KC8

protein_coding

tolerated(0.14)

benign(0.038)

TCGA-Q1-A73P-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DNAJC1

SNV

Missense_Mutation

c.332N>T

p.Ala111Val

p.A111V

Q96KC8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A6-6780-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

DNAJC1

SNV

Missense_Mutation

c.1439G>T

p.Ser480Ile

p.S480I

Q96KC8

protein_coding

deleterious(0.03)

probably_damaging(0.994)

TCGA-AD-5900-01

Colorectum

colon adenocarcinoma

Male

>=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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