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: HSPA1B

Gene summary for HSPA1B

Gene summary.

Gene information	Species	Human
	Gene symbol	HSPA1B
	Gene ID	3304
	Gene name	heat shock protein family A (Hsp70) member 1B
	Gene Alias	HSP70-1
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0000226
	UniProtAcc	A8K5I0

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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
3304	HSPA1B	GSM4909277	Human	Breast	Precancer	3.11e-04	8.81e-01	0.0177
3304	HSPA1B	GSM4909280	Human	Breast	Precancer	7.10e-04	6.57e-01	0.0305
3304	HSPA1B	GSM4909281	Human	Breast	IDC	2.18e-07	3.68e-01	0.21
3304	HSPA1B	GSM4909282	Human	Breast	IDC	2.25e-15	-7.29e-01	-0.0288
3304	HSPA1B	GSM4909285	Human	Breast	IDC	9.70e-10	-4.91e-01	0.21
3304	HSPA1B	GSM4909286	Human	Breast	IDC	2.41e-19	-8.05e-01	0.1081
3304	HSPA1B	GSM4909287	Human	Breast	IDC	1.16e-04	-5.59e-01	0.2057
3304	HSPA1B	GSM4909288	Human	Breast	IDC	3.80e-04	-7.99e-01	0.0988
3304	HSPA1B	GSM4909291	Human	Breast	IDC	4.18e-12	5.29e-01	0.1753
3304	HSPA1B	GSM4909293	Human	Breast	IDC	1.11e-16	-7.60e-01	0.1581
3304	HSPA1B	GSM4909294	Human	Breast	IDC	2.91e-13	-7.63e-01	0.2022
3304	HSPA1B	GSM4909297	Human	Breast	IDC	8.20e-04	2.11e-01	0.1517
3304	HSPA1B	GSM4909298	Human	Breast	IDC	2.07e-02	-9.87e-02	0.1551
3304	HSPA1B	GSM4909299	Human	Breast	IDC	3.15e-11	4.36e-01	0.035
3304	HSPA1B	GSM4909302	Human	Breast	IDC	8.76e-18	-8.30e-01	0.1545
3304	HSPA1B	GSM4909304	Human	Breast	IDC	2.24e-05	7.63e-02	0.1636
3304	HSPA1B	GSM4909305	Human	Breast	IDC	3.73e-03	-1.87e-02	0.0436
3304	HSPA1B	GSM4909306	Human	Breast	IDC	1.04e-04	6.75e-03	0.1564
3304	HSPA1B	GSM4909308	Human	Breast	IDC	1.55e-07	2.15e-01	0.158
3304	HSPA1B	GSM4909311	Human	Breast	IDC	1.32e-11	-3.22e-01	0.1534

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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
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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:00621979	Breast	Precancer	cellular response to chemical stress	51/1080	337/18723	2.40e-10	2.34e-08	51
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:20012349	Breast	Precancer	negative regulation of apoptotic signaling pathway	39/1080	224/18723	5.35e-10	4.77e-08	39
GO:00064588	Breast	Precancer	'de novo' protein folding	16/1080	43/18723	8.14e-10	6.92e-08	16
GO:00190589	Breast	Precancer	viral life cycle	47/1080	317/18723	2.42e-09	1.99e-07	47
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:00458629	Breast	Precancer	positive regulation of proteolysis	51/1080	372/18723	7.77e-09	5.70e-07	51
GO:00510848	Breast	Precancer	'de novo' posttranslational protein folding	14/1080	39/18723	1.61e-08	1.12e-06	14
GO:19033209	Breast	Precancer	regulation of protein modification by small protein conjugation or removal	38/1080	242/18723	1.71e-08	1.17e-06	38
GO:00510858	Breast	Precancer	chaperone cofactor-dependent protein refolding	13/1080	34/18723	2.17e-08	1.47e-06	13
GO:00345999	Breast	Precancer	cellular response to oxidative stress	42/1080	288/18723	2.78e-08	1.79e-06	42
GO:00359669	Breast	Precancer	response to topologically incorrect protein	29/1080	159/18723	3.00e-08	1.89e-06	29
GO:00444039	Breast	Precancer	biological process involved in symbiotic interaction	42/1080	290/18723	3.40e-08	2.11e-06	42
GO:19033219	Breast	Precancer	negative regulation of protein modification by small protein conjugation or removal	21/1080	95/18723	8.09e-08	4.61e-06	21
GO:00346209	Breast	Precancer	cellular response to unfolded protein	21/1080	96/18723	9.80e-08	5.46e-06	21

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0502016	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0513414	Breast	Precancer	Legionellosis	19/684	57/8465	4.62e-08	9.12e-07	6.98e-07	19
hsa030408	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0491518	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0541718	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0461218	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0502017	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0513415	Breast	Precancer	Legionellosis	19/684	57/8465	4.62e-08	9.12e-07	6.98e-07	19
hsa0304013	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0491519	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0541719	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0461219	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0502023	Breast	IDC	Prion disease	102/867	273/8465	3.70e-34	4.01e-32	3.00e-32	102
hsa0491523	Breast	IDC	Estrogen signaling pathway	35/867	138/8465	2.55e-07	5.18e-06	3.88e-06	35
hsa0461223	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24
hsa0513422	Breast	IDC	Legionellosis	19/867	57/8465	1.89e-06	3.07e-05	2.29e-05	19
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0304023	Breast	IDC	Spliceosome	40/867	217/8465	1.53e-04	1.42e-03	1.06e-03	40

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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

HSPA1B

SNV

Missense_Mutation

rs199562339

c.5C>T

p.Ala2Val

p.A2V

P0DMV9

protein_coding

tolerated_low_confidence(0.09)

benign(0.251)

TCGA-B6-A0RS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HSPA1B

SNV

Missense_Mutation

novel

c.21N>G

p.Ile7Met

p.I7M

P0DMV9

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.966)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HSPA1B

SNV

Missense_Mutation

novel

c.1916A>G

p.Glu639Gly

p.E639G

P0DMV9

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.932)

TCGA-EA-A410-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HSPA1B

SNV

Missense_Mutation

rs757789364

c.1704N>C

p.Lys568Asn

p.K568N

P0DMV9

protein_coding

tolerated_low_confidence(0.16)

benign(0.007)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HSPA1B

SNV

Missense_Mutation

novel

c.101N>A

p.Gly34Asp

p.G34D

P0DMV9

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AD-6964-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folfox

HSPA1B

SNV

Missense_Mutation

novel

c.1662N>T

p.Glu554Asp

p.E554D

P0DMV9

protein_coding

tolerated_low_confidence(0.3)

benign(0.039)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

HSPA1B

SNV

Missense_Mutation

c.71N>A

p.Gly24Asp

p.G24D

P0DMV9

protein_coding

tolerated_low_confidence(0.4)

probably_damaging(0.957)

TCGA-QG-A5Z2-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

HSPA1B

SNV

Missense_Mutation

novel

c.34N>A

p.Gly12Ser

p.G12S

P0DMV9

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-AX-A3FT-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

HSPA1B

SNV

Missense_Mutation

novel

c.44N>C

p.Tyr15Ser

p.Y15S

P0DMV9

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.971)

TCGA-33-AAS8-01

Lung

lung squamous cell carcinoma

Female

<65

I/II

Unknown

HSPA1B

insertion

Frame_Shift_Ins

novel

c.1925_1926insG

p.Ter642%3D

p.*642%3D

P0DMV9

protein_coding

TCGA-50-5066-01

Lung

lung adenocarcinoma

Male

>=65

I/II

Chemotherapy

carboplatin

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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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