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: BAG1

Gene summary for BAG1

Gene summary.

Gene information	Species	Human
	Gene symbol	BAG1
	Gene ID	573
	Gene name	BAG cochaperone 1
	Gene Alias	BAG-1
	Cytomap	9p13.3
	Gene Type	protein-coding
	GO ID	GO:0006457
	UniProtAcc	Q99933

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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
573	BAG1	P76T-E	Human	Esophagus	ESCC	3.01e-14	5.06e-01	0.1207
573	BAG1	P79T-E	Human	Esophagus	ESCC	6.14e-15	6.54e-01	0.1154
573	BAG1	P80T-E	Human	Esophagus	ESCC	5.60e-65	2.72e+00	0.155
573	BAG1	P82T-E	Human	Esophagus	ESCC	1.08e-25	1.46e+00	0.1072
573	BAG1	P83T-E	Human	Esophagus	ESCC	1.44e-23	9.06e-01	0.1738
573	BAG1	P84T-E	Human	Esophagus	ESCC	1.69e-15	1.08e+00	0.0933
573	BAG1	P89T-E	Human	Esophagus	ESCC	9.62e-16	1.36e+00	0.1752
573	BAG1	P91T-E	Human	Esophagus	ESCC	4.03e-07	1.21e+00	0.1828
573	BAG1	P104T-E	Human	Esophagus	ESCC	1.08e-02	7.20e-01	0.0931
573	BAG1	P107T-E	Human	Esophagus	ESCC	3.10e-35	1.02e+00	0.171
573	BAG1	P126T-E	Human	Esophagus	ESCC	1.24e-05	1.28e+00	0.1125
573	BAG1	P127T-E	Human	Esophagus	ESCC	1.54e-37	6.79e-01	0.0826
573	BAG1	P128T-E	Human	Esophagus	ESCC	3.92e-67	2.90e+00	0.1241
573	BAG1	P130T-E	Human	Esophagus	ESCC	8.53e-75	2.51e+00	0.1676
573	BAG1	S43	Human	Liver	Cirrhotic	1.69e-03	-1.82e-01	-0.0187
573	BAG1	HCC1_Meng	Human	Liver	HCC	3.47e-72	1.07e-01	0.0246
573	BAG1	HCC2_Meng	Human	Liver	HCC	1.22e-38	6.41e-02	0.0107
573	BAG1	cirrhotic1	Human	Liver	Cirrhotic	1.62e-13	2.89e-01	0.0202
573	BAG1	cirrhotic2	Human	Liver	Cirrhotic	2.10e-15	2.97e-01	0.0201
573	BAG1	cirrhotic3	Human	Liver	Cirrhotic	3.31e-09	2.29e-01	0.0215

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0031647	Colorectum	AD	regulation of protein stability	108/3918	298/18723	6.33e-10	5.08e-08	108
GO:0050821	Colorectum	AD	protein stabilization	73/3918	191/18723	3.02e-08	1.64e-06	73
GO:0006457	Colorectum	AD	protein folding	73/3918	212/18723	3.24e-06	9.10e-05	73
GO:0006458	Colorectum	AD	'de novo' protein folding	20/3918	43/18723	1.53e-04	2.16e-03	20
GO:0051084	Colorectum	AD	'de novo' posttranslational protein folding	18/3918	39/18723	3.66e-04	4.24e-03	18
GO:0061077	Colorectum	AD	chaperone-mediated protein folding	26/3918	67/18723	6.20e-04	6.48e-03	26
GO:0051085	Colorectum	AD	chaperone cofactor-dependent protein refolding	15/3918	34/18723	1.96e-03	1.58e-02	15
GO:00316471	Colorectum	SER	regulation of protein stability	86/2897	298/18723	2.56e-09	2.42e-07	86
GO:00508211	Colorectum	SER	protein stabilization	58/2897	191/18723	1.46e-07	8.59e-06	58
GO:00064571	Colorectum	SER	protein folding	54/2897	212/18723	1.04e-04	2.18e-03	54
GO:00610771	Colorectum	SER	chaperone-mediated protein folding	21/2897	67/18723	8.44e-04	1.04e-02	21
GO:00064581	Colorectum	SER	'de novo' protein folding	15/2897	43/18723	1.36e-03	1.51e-02	15
GO:00510851	Colorectum	SER	chaperone cofactor-dependent protein refolding	12/2897	34/18723	3.60e-03	3.03e-02	12
GO:00510841	Colorectum	SER	'de novo' posttranslational protein folding	13/2897	39/18723	4.39e-03	3.51e-02	13
GO:00316472	Colorectum	MSS	regulation of protein stability	103/3467	298/18723	2.52e-11	3.49e-09	103
GO:00508212	Colorectum	MSS	protein stabilization	68/3467	191/18723	1.53e-08	8.81e-07	68
GO:00064572	Colorectum	MSS	protein folding	71/3467	212/18723	1.25e-07	5.91e-06	71
GO:00064582	Colorectum	MSS	'de novo' protein folding	20/3467	43/18723	2.50e-05	5.21e-04	20
GO:00510842	Colorectum	MSS	'de novo' posttranslational protein folding	18/3467	39/18723	7.19e-05	1.21e-03	18
GO:00610772	Colorectum	MSS	chaperone-mediated protein folding	26/3467	67/18723	8.06e-05	1.33e-03	26

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
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
hsa041416	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa041417	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
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
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141210	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113
hsa0414138	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113
hsa0414145	Oral cavity	EOLP	Protein processing in endoplasmic reticulum	70/1218	174/8465	2.84e-17	3.06e-15	1.81e-15	70
hsa0414155	Oral cavity	EOLP	Protein processing in endoplasmic reticulum	70/1218	174/8465	2.84e-17	3.06e-15	1.81e-15	70

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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

BAG1

SNV

Missense_Mutation

novel

c.969C>A

p.Asp323Glu

p.D323E

protein_coding

deleterious(0.02)

probably_damaging(0.914)

TCGA-BH-A0BD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

BAG1

SNV

Missense_Mutation

novel

c.631G>A

p.Asp211Asn

p.D211N

protein_coding

tolerated(1)

benign(0.005)

TCGA-BH-A5J0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BAG1

SNV

Missense_Mutation

novel

c.767G>C

p.Gly256Ala

p.G256A

protein_coding

deleterious(0.03)

probably_damaging(0.982)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

BAG1

SNV

Missense_Mutation

novel

c.457N>A

p.Glu153Lys

p.E153K

protein_coding

tolerated(0.13)

benign(0.237)

TCGA-C5-A3HL-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

BAG1

deletion

Frame_Shift_Del

c.941delN

p.Lys314ArgfsTer6

p.K314Rfs*6

protein_coding

TCGA-A6-6780-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

BAG1

deletion

Frame_Shift_Del

c.941delN

p.Lys314ArgfsTer6

p.K314Rfs*6

protein_coding

TCGA-AG-A02N-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Chemotherapy

folinic

BAG1

SNV

Missense_Mutation

rs867677136

c.401N>C

p.Val134Ala

p.V134A

protein_coding

tolerated_low_confidence(0.15)

benign(0.005)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

BAG1

SNV

Missense_Mutation

novel

c.976N>A

p.Glu326Lys

p.E326K

protein_coding

tolerated(0.08)

possibly_damaging(0.655)

TCGA-A5-A7WK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

BAG1

SNV

Missense_Mutation

c.901T>G

p.Phe301Val

p.F301V

protein_coding

deleterious(0.02)

possibly_damaging(0.863)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

BAG1

SNV

Missense_Mutation

c.220N>G

p.Lys74Glu

p.K74E

protein_coding

deleterious_low_confidence(0)

benign(0.017)

TCGA-B5-A11H-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Hormone Therapy

megace

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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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