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:004586118	Prostate	BPH	negative regulation of proteolysis	98/3107	351/18723	5.43e-08	1.49e-06	98
GO:00015039	Prostate	BPH	ossification	107/3107	408/18723	4.31e-07	8.83e-06	107
GO:007265516	Prostate	BPH	establishment of protein localization to mitochondrion	42/3107	120/18723	7.32e-07	1.39e-05	42
GO:007058516	Prostate	BPH	protein localization to mitochondrion	43/3107	125/18723	9.29e-07	1.70e-05	43
GO:001703810	Prostate	BPH	protein import	62/3107	206/18723	9.72e-07	1.77e-05	62
GO:00160507	Prostate	BPH	vesicle organization	82/3107	300/18723	1.64e-06	2.78e-05	82
GO:003497516	Prostate	BPH	protein folding in endoplasmic reticulum	9/3107	11/18723	3.77e-06	5.81e-05	9
GO:00164828	Prostate	BPH	cytosolic transport	51/3107	168/18723	6.56e-06	9.53e-05	51
GO:000662616	Prostate	BPH	protein targeting to mitochondrion	34/3107	100/18723	1.64e-05	2.05e-04	34
GO:00068989	Prostate	BPH	receptor-mediated endocytosis	66/3107	244/18723	2.34e-05	2.80e-04	66
GO:199054210	Prostate	BPH	mitochondrial transmembrane transport	34/3107	102/18723	2.63e-05	3.10e-04	34
GO:00365034	Prostate	BPH	ERAD pathway	35/3107	107/18723	3.17e-05	3.60e-04	35
GO:007005917	Prostate	BPH	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	24/3107	63/18723	3.48e-05	3.87e-04	24
GO:00304333	Prostate	BPH	ubiquitin-dependent ERAD pathway	29/3107	85/18723	6.22e-05	6.23e-04	29
GO:00327814	Prostate	BPH	positive regulation of ATPase activity	13/3107	27/18723	1.40e-04	1.25e-03	13
GO:00989276	Prostate	BPH	vesicle-mediated transport between endosomal compartments	17/3107	43/18723	2.81e-04	2.19e-03	17
GO:00075483	Prostate	BPH	sex differentiation	68/3107	276/18723	3.75e-04	2.76e-03	68
GO:00070326	Prostate	BPH	endosome organization	26/3107	82/18723	5.42e-04	3.81e-03	26
GO:00450224	Prostate	BPH	early endosome to late endosome transport	15/3107	40/18723	1.21e-03	7.41e-03	15
GO:00434625	Prostate	BPH	regulation of ATPase activity	16/3107	46/18723	2.11e-03	1.18e-02	16

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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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