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: DNAJB6

Gene summary for DNAJB6

Gene summary.

Gene information	Species	Human
	Gene symbol	DNAJB6
	Gene ID	10049
	Gene name	DnaJ heat shock protein family (Hsp40) member B6
	Gene Alias	DJ4
	Cytomap	7q36.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	O75190

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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
10049	DNAJB6	GSM4909277	Human	Breast	Precancer	2.94e-04	5.68e-01	0.0177
10049	DNAJB6	GSM4909285	Human	Breast	IDC	9.39e-10	-3.61e-01	0.21
10049	DNAJB6	GSM4909286	Human	Breast	IDC	1.64e-05	1.77e-02	0.1081
10049	DNAJB6	GSM4909290	Human	Breast	IDC	1.92e-14	-5.39e-01	0.2096
10049	DNAJB6	GSM4909293	Human	Breast	IDC	3.57e-10	-3.13e-01	0.1581
10049	DNAJB6	GSM4909294	Human	Breast	IDC	1.47e-08	-3.14e-01	0.2022
10049	DNAJB6	GSM4909296	Human	Breast	IDC	3.64e-25	-5.97e-01	0.1524
10049	DNAJB6	GSM4909297	Human	Breast	IDC	3.16e-22	-3.63e-01	0.1517
10049	DNAJB6	GSM4909301	Human	Breast	IDC	5.01e-06	-3.72e-01	0.1577
10049	DNAJB6	GSM4909302	Human	Breast	IDC	1.19e-03	-3.08e-01	0.1545
10049	DNAJB6	GSM4909304	Human	Breast	IDC	3.33e-11	-4.20e-01	0.1636
10049	DNAJB6	GSM4909306	Human	Breast	IDC	3.75e-02	-2.02e-01	0.1564
10049	DNAJB6	GSM4909307	Human	Breast	IDC	7.16e-05	-3.55e-01	0.1569
10049	DNAJB6	GSM4909309	Human	Breast	IDC	7.84e-08	-4.02e-01	0.0483
10049	DNAJB6	GSM4909311	Human	Breast	IDC	2.86e-45	-6.57e-01	0.1534
10049	DNAJB6	GSM4909312	Human	Breast	IDC	1.10e-14	-3.46e-01	0.1552
10049	DNAJB6	GSM4909313	Human	Breast	IDC	1.76e-03	-2.27e-01	0.0391
10049	DNAJB6	GSM4909316	Human	Breast	IDC	1.17e-06	-4.48e-01	0.21
10049	DNAJB6	GSM4909319	Human	Breast	IDC	6.89e-50	-6.04e-01	0.1563
10049	DNAJB6	GSM4909320	Human	Breast	IDC	2.83e-14	-6.60e-01	0.1575

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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
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
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:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:20001169	Breast	Precancer	regulation of cysteine-type endopeptidase activity	43/1080	235/18723	1.30e-11	1.83e-09	43
GO:00432819	Breast	Precancer	regulation of cysteine-type endopeptidase activity involved in apoptotic process	40/1080	209/18723	1.59e-11	2.07e-09	40
GO:00458619	Breast	Precancer	negative regulation of proteolysis	50/1080	351/18723	2.99e-09	2.39e-07	50
GO:00610778	Breast	Precancer	chaperone-mediated protein folding	19/1080	67/18723	4.22e-09	3.28e-07	19
GO:00513468	Breast	Precancer	negative regulation of hydrolase activity	50/1080	379/18723	3.85e-08	2.34e-06	50
GO:00104668	Breast	Precancer	negative regulation of peptidase activity	38/1080	262/18723	1.46e-07	7.82e-06	38
GO:00109519	Breast	Precancer	negative regulation of endopeptidase activity	37/1080	252/18723	1.55e-07	8.05e-06	37
GO:20001179	Breast	Precancer	negative regulation of cysteine-type endopeptidase activity	19/1080	86/18723	3.36e-07	1.58e-05	19
GO:00431548	Breast	Precancer	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	17/1080	78/18723	1.69e-06	6.08e-05	17
GO:00092667	Breast	Precancer	response to temperature stimulus	27/1080	178/18723	3.85e-06	1.21e-04	27
GO:00346059	Breast	Precancer	cellular response to heat	15/1080	69/18723	7.08e-06	1.95e-04	15
GO:00094088	Breast	Precancer	response to heat	18/1080	110/18723	5.57e-05	1.15e-03	18
GO:0045104	Breast	Precancer	intermediate filament cytoskeleton organization	11/1080	51/18723	1.26e-04	2.22e-03	11
GO:0045103	Breast	Precancer	intermediate filament-based process	11/1080	52/18723	1.52e-04	2.60e-03	11
GO:00018927	Breast	Precancer	embryonic placenta development	14/1080	82/18723	2.30e-04	3.48e-03	14
GO:00486087	Breast	Precancer	reproductive structure development	43/1080	424/18723	2.36e-04	3.56e-03	43
GO:00614587	Breast	Precancer	reproductive system development	43/1080	427/18723	2.75e-04	4.00e-03	43

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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

DNAJB6

SNV

Missense_Mutation

c.626N>C

p.Val209Ala

p.V209A

O75190

protein_coding

deleterious(0)

benign(0.079)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DNAJB6

insertion

Nonsense_Mutation

novel

c.216_217insAACATGGTCATTGTTCTTGCCATGGCACTGGCTACCTGAAACTGC

p.Gly72_Leu73insAsnMetValIleValLeuAlaMetAlaLeuAlaThrTerAsnCys

p.G72_L73insNMVIVLAMALAT*NC

O75190

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

DNAJB6

deletion

Frame_Shift_Del

novel

c.418delN

p.Phe141SerfsTer27

p.F141Sfs*27

O75190

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

DNAJB6

SNV

Missense_Mutation

c.337G>C

p.Asp113His

p.D113H

O75190

protein_coding

tolerated(0.37)

possibly_damaging(0.65)

TCGA-C5-A1MK-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

carboplatin

DNAJB6

SNV

Missense_Mutation

novel

c.954N>C

p.Lys318Asn

p.K318N

O75190

protein_coding

deleterious(0.01)

possibly_damaging(0.666)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DNAJB6

SNV

Missense_Mutation

novel

c.479N>A

p.Gly160Glu

p.G160E

O75190

protein_coding

tolerated(0.05)

probably_damaging(0.999)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

DNAJB6

SNV

Missense_Mutation

c.569N>T

p.Ser190Leu

p.S190L

O75190

protein_coding

deleterious(0.02)

probably_damaging(0.992)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

DNAJB6

SNV

Missense_Mutation

c.70N>T

p.Arg24Trp

p.R24W

O75190

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-CK-4947-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Other, specify in notes

folinic

DNAJB6

SNV

Missense_Mutation

c.851N>T

p.Asp284Val

p.D284V

O75190

protein_coding

deleterious(0.02)

benign(0.044)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

DNAJB6

SNV

Missense_Mutation

novel

c.567A>C

p.Lys189Asn

p.K189N

O75190

protein_coding

tolerated(0.09)

possibly_damaging(0.558)

TCGA-F5-6814-01

Colorectum

rectum 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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