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: DNAJB1

Gene summary for DNAJB1

Gene summary.

Gene information	Species	Human
	Gene symbol	DNAJB1
	Gene ID	3337
	Gene name	DnaJ heat shock protein family (Hsp40) member B1
	Gene Alias	HSPF1
	Cytomap	19p13.12
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P25685

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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
3337	DNAJB1	GSM4909277	Human	Breast	Precancer	8.34e-04	8.68e-01	0.0177
3337	DNAJB1	GSM4909281	Human	Breast	IDC	4.15e-02	-2.37e-01	0.21
3337	DNAJB1	GSM4909285	Human	Breast	IDC	3.35e-08	-2.53e-01	0.21
3337	DNAJB1	GSM4909286	Human	Breast	IDC	9.25e-11	-5.89e-01	0.1081
3337	DNAJB1	GSM4909291	Human	Breast	IDC	3.12e-07	4.90e-01	0.1753
3337	DNAJB1	GSM4909293	Human	Breast	IDC	2.23e-05	-1.83e-01	0.1581
3337	DNAJB1	GSM4909294	Human	Breast	IDC	4.20e-07	-5.85e-01	0.2022
3337	DNAJB1	GSM4909298	Human	Breast	IDC	1.25e-05	-9.04e-02	0.1551
3337	DNAJB1	GSM4909301	Human	Breast	IDC	1.55e-05	3.32e-01	0.1577
3337	DNAJB1	GSM4909304	Human	Breast	IDC	3.98e-11	2.87e-01	0.1636
3337	DNAJB1	GSM4909305	Human	Breast	IDC	1.38e-03	3.54e-02	0.0436
3337	DNAJB1	GSM4909306	Human	Breast	IDC	9.79e-03	9.55e-02	0.1564
3337	DNAJB1	GSM4909307	Human	Breast	IDC	4.19e-02	-4.29e-01	0.1569
3337	DNAJB1	GSM4909308	Human	Breast	IDC	1.09e-04	-9.22e-02	0.158
3337	DNAJB1	GSM4909311	Human	Breast	IDC	8.73e-16	-5.47e-01	0.1534
3337	DNAJB1	GSM4909312	Human	Breast	IDC	1.58e-06	-4.91e-01	0.1552
3337	DNAJB1	GSM4909317	Human	Breast	IDC	3.75e-19	6.49e-01	0.1355
3337	DNAJB1	GSM4909319	Human	Breast	IDC	6.20e-15	-1.16e-01	0.1563
3337	DNAJB1	brca1	Human	Breast	Precancer	3.83e-12	-6.32e-01	-0.0338
3337	DNAJB1	brca2	Human	Breast	Precancer	4.63e-13	-5.82e-01	-0.024

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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
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
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
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:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:00064588	Breast	Precancer	'de novo' protein folding	16/1080	43/18723	8.14e-10	6.92e-08	16
GO:00069869	Breast	Precancer	response to unfolded protein	28/1080	137/18723	3.81e-09	3.00e-07	28
GO:00610778	Breast	Precancer	chaperone-mediated protein folding	19/1080	67/18723	4.22e-09	3.28e-07	19
GO:00510848	Breast	Precancer	'de novo' posttranslational protein folding	14/1080	39/18723	1.61e-08	1.12e-06	14
GO:00510858	Breast	Precancer	chaperone cofactor-dependent protein refolding	13/1080	34/18723	2.17e-08	1.47e-06	13
GO:00359669	Breast	Precancer	response to topologically incorrect protein	29/1080	159/18723	3.00e-08	1.89e-06	29
GO:00092667	Breast	Precancer	response to temperature stimulus	27/1080	178/18723	3.85e-06	1.21e-04	27
GO:00436209	Breast	Precancer	regulation of DNA-templated transcription in response to stress	13/1080	53/18723	7.06e-06	1.95e-04	13
GO:00346059	Breast	Precancer	cellular response to heat	15/1080	69/18723	7.08e-06	1.95e-04	15
GO:00436189	Breast	Precancer	regulation of transcription from RNA polymerase II promoter in response to stress	12/1080	47/18723	1.02e-05	2.67e-04	12
GO:00094088	Breast	Precancer	response to heat	18/1080	110/18723	5.57e-05	1.15e-03	18
GO:00434624	Breast	Precancer	regulation of ATPase activity	10/1080	46/18723	2.38e-04	3.57e-03	10
GO:00708417	Breast	Precancer	inclusion body assembly	6/1080	24/18723	1.99e-03	1.90e-02	6
GO:00900836	Breast	Precancer	regulation of inclusion body assembly	5/1080	17/18723	2.19e-03	2.06e-02	5
GO:00900847	Breast	Precancer	negative regulation of inclusion body assembly	4/1080	11/18723	2.62e-03	2.34e-02	4
GO:00972017	Breast	Precancer	negative regulation of transcription from RNA polymerase II promoter in response to stress	4/1080	12/18723	3.75e-03	3.04e-02	4
GO:00327813	Breast	Precancer	positive regulation of ATPase activity	6/1080	27/18723	3.78e-03	3.04e-02	6
GO:000645713	Breast	IDC	protein folding	47/1434	212/18723	2.31e-11	3.86e-09	47
GO:006107713	Breast	IDC	chaperone-mediated protein folding	21/1434	67/18723	1.35e-08	9.71e-07	21

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
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
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0516414	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0516415	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa0516422	Cervix	HSIL_HPV	Influenza A	23/459	171/8465	4.65e-05	6.48e-04	5.24e-04	23
hsa0516432	Cervix	HSIL_HPV	Influenza A	23/459	171/8465	4.65e-05	6.48e-04	5.24e-04	23
hsa0414144	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa0516441	Cervix	N_HPV	Influenza A	16/349	171/8465	1.81e-03	1.12e-02	8.75e-03	16
hsa0414154	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa0516451	Cervix	N_HPV	Influenza A	16/349	171/8465	1.81e-03	1.12e-02	8.75e-03	16
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
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60

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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

DNAJB1

SNV

Missense_Mutation

c.148N>C

p.Glu50Gln

p.E50Q

P25685

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DNAJB1

SNV

Missense_Mutation

c.514C>A

p.Leu172Ile

p.L172I

P25685

protein_coding

deleterious(0.01)

probably_damaging(0.975)

TCGA-D8-A1JC-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

DNAJB1

insertion

Frame_Shift_Ins

novel

c.387_388insAGTTTCCAGGTGTCTTG

p.Pro130SerfsTer21

p.P130Sfs*21

P25685

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DNAJB1

SNV

Missense_Mutation

rs768130288

c.52N>A

p.Glu18Lys

p.E18K

P25685

protein_coding

deleterious(0.04)

benign(0.16)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

DNAJB1

SNV

Missense_Mutation

c.746G>A

p.Arg249Lys

p.R249K

P25685

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-DS-A0VN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DNAJB1

insertion

Frame_Shift_Ins

novel

c.612_613insGGGTCTC

p.Thr205GlyfsTer32

p.T205Gfs*32

P25685

protein_coding

TCGA-C5-A2LY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DNAJB1

insertion

Nonsense_Mutation

novel

c.610_611insCCTGATTTTTTTTTTTTAA

p.Leu204SerfsTer2

p.L204Sfs*2

P25685

protein_coding

TCGA-C5-A2LY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DNAJB1

SNV

Missense_Mutation

novel

c.419N>A

p.Gly140Asp

p.G140D

P25685

protein_coding

tolerated(0.05)

possibly_damaging(0.901)

TCGA-AA-3856-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

DNAJB1

SNV

Missense_Mutation

c.210N>C

p.Glu70Asp

p.E70D

P25685

protein_coding

tolerated(0.14)

benign(0.076)

TCGA-G4-6628-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

DNAJB1

insertion

Frame_Shift_Ins

novel

c.581_582insCCATCTCTCTT

p.Lys195HisfsTer4

p.K195Hfs*4

P25685

protein_coding

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

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
3337	DNAJB1	NA		HSP70		15047721,16533811,15115283

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