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: BAP1

Gene summary for BAP1

Gene summary.

Gene information	Species	Human
	Gene symbol	BAP1
	Gene ID	8314
	Gene name	BRCA1 associated protein 1
	Gene Alias	HUCEP-13
	Cytomap	3p21.1
	Gene Type	protein-coding
	GO ID	GO:0001558
	UniProtAcc	A0A024R305

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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
8314	BAP1	LZE4T	Human	Esophagus	ESCC	2.82e-04	8.17e-02	0.0811
8314	BAP1	LZE7T	Human	Esophagus	ESCC	1.77e-06	1.12e-01	0.0667
8314	BAP1	LZE22T	Human	Esophagus	ESCC	1.69e-02	9.17e-02	0.068
8314	BAP1	LZE24T	Human	Esophagus	ESCC	8.83e-09	1.65e-01	0.0596
8314	BAP1	LZE21T	Human	Esophagus	ESCC	9.20e-07	2.65e-01	0.0655
8314	BAP1	P1T-E	Human	Esophagus	ESCC	4.09e-06	2.30e-01	0.0875
8314	BAP1	P2T-E	Human	Esophagus	ESCC	1.95e-15	2.87e-01	0.1177
8314	BAP1	P4T-E	Human	Esophagus	ESCC	1.79e-20	2.15e-01	0.1323
8314	BAP1	P5T-E	Human	Esophagus	ESCC	2.60e-10	2.58e-02	0.1327
8314	BAP1	P8T-E	Human	Esophagus	ESCC	5.99e-07	1.17e-01	0.0889
8314	BAP1	P9T-E	Human	Esophagus	ESCC	1.51e-17	2.84e-01	0.1131
8314	BAP1	P10T-E	Human	Esophagus	ESCC	4.55e-28	6.78e-01	0.116
8314	BAP1	P11T-E	Human	Esophagus	ESCC	1.03e-08	1.79e-01	0.1426
8314	BAP1	P12T-E	Human	Esophagus	ESCC	1.17e-17	3.87e-01	0.1122
8314	BAP1	P15T-E	Human	Esophagus	ESCC	2.10e-24	4.34e-01	0.1149
8314	BAP1	P16T-E	Human	Esophagus	ESCC	1.33e-09	2.16e-02	0.1153
8314	BAP1	P17T-E	Human	Esophagus	ESCC	2.09e-04	5.66e-02	0.1278
8314	BAP1	P20T-E	Human	Esophagus	ESCC	2.17e-07	1.99e-02	0.1124
8314	BAP1	P21T-E	Human	Esophagus	ESCC	1.93e-14	1.37e-01	0.1617
8314	BAP1	P22T-E	Human	Esophagus	ESCC	1.59e-12	1.44e-01	0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0072594110	Esophagus	ESCC	establishment of protein localization to organelle	311/8552	422/18723	3.02e-32	2.13e-29	311
GO:001657015	Esophagus	ESCC	histone modification	323/8552	463/18723	2.61e-26	7.88e-24	323
GO:003238618	Esophagus	ESCC	regulation of intracellular transport	243/8552	337/18723	3.20e-23	7.25e-21	243
GO:0006605111	Esophagus	ESCC	protein targeting	229/8552	314/18723	4.93e-23	1.01e-20	229
GO:0006839110	Esophagus	ESCC	mitochondrial transport	187/8552	254/18723	8.35e-20	9.81e-18	187
GO:1903829111	Esophagus	ESCC	positive regulation of cellular protein localization	199/8552	276/18723	2.99e-19	3.45e-17	199
GO:0033157110	Esophagus	ESCC	regulation of intracellular protein transport	169/8552	229/18723	3.31e-18	3.23e-16	169
GO:0032388110	Esophagus	ESCC	positive regulation of intracellular transport	152/8552	202/18723	7.89e-18	7.36e-16	152
GO:1904951111	Esophagus	ESCC	positive regulation of establishment of protein localization	216/8552	319/18723	1.01e-15	6.86e-14	216
GO:0072655110	Esophagus	ESCC	establishment of protein localization to mitochondrion	97/8552	120/18723	2.17e-15	1.33e-13	97
GO:009031617	Esophagus	ESCC	positive regulation of intracellular protein transport	122/8552	160/18723	2.45e-15	1.49e-13	122
GO:0070585110	Esophagus	ESCC	protein localization to mitochondrion	100/8552	125/18723	2.96e-15	1.77e-13	100
GO:0051222111	Esophagus	ESCC	positive regulation of protein transport	204/8552	303/18723	1.56e-14	8.38e-13	204
GO:0006626110	Esophagus	ESCC	protein targeting to mitochondrion	81/8552	100/18723	3.60e-13	1.67e-11	81
GO:0016049110	Esophagus	ESCC	cell growth	289/8552	482/18723	1.29e-10	3.77e-09	289
GO:000155819	Esophagus	ESCC	regulation of cell growth	248/8552	414/18723	2.97e-09	6.45e-08	248
GO:0002262111	Esophagus	ESCC	myeloid cell homeostasis	104/8552	157/18723	1.49e-07	2.36e-06	104
GO:0048872111	Esophagus	ESCC	homeostasis of number of cells	163/8552	272/18723	1.40e-06	1.69e-05	163
GO:190353315	Esophagus	ESCC	regulation of protein targeting	57/8552	81/18723	5.83e-06	6.03e-05	57
GO:190374715	Esophagus	ESCC	regulation of establishment of protein localization to mitochondrion	37/8552	50/18723	4.42e-05	3.51e-04	37

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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

BAP1

SNV

Missense_Mutation

novel

c.626N>G

p.Val209Gly

p.V209G

Q92560

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A2-A0CS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

BAP1

SNV

Missense_Mutation

c.145C>G

p.Leu49Val

p.L49V

Q92560

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

BAP1

SNV

Missense_Mutation

c.1195G>A

p.Asp399Asn

p.D399N

Q92560

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.984)

TCGA-A2-A0YD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

BAP1

SNV

Missense_Mutation

c.134N>A

p.Gly45Glu

p.G45E

Q92560

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A2-A0YE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Taxotere

BAP1

SNV

Missense_Mutation

c.131N>G

p.Tyr44Cys

p.Y44C

Q92560

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BAP1

SNV

Missense_Mutation

c.709N>T

p.Arg237Cys

p.R237C

Q92560

protein_coding

deleterious(0.05)

probably_damaging(0.976)

TCGA-BH-A0GY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyotxan

BAP1

SNV

Missense_Mutation

c.599N>G

p.Glu200Gly

p.E200G

Q92560

protein_coding

deleterious(0.02)

benign(0.352)

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BAP1

SNV

Missense_Mutation

c.1291N>A

p.Gly431Ser

p.G431S

Q92560

protein_coding

tolerated_low_confidence(0.34)

benign(0)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

BAP1

SNV

Missense_Mutation

novel

c.1696G>A

p.Glu566Lys

p.E566K

Q92560

protein_coding

tolerated_low_confidence(0.11)

benign(0.001)

TCGA-C8-A3M7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

BAP1

SNV

Missense_Mutation

rs375129361

c.277N>G

p.Thr93Ala

p.T93A

Q92560

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-E2-A573-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

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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
8314	BAP1	PROTEASE, TUMOR SUPPRESSOR, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		APITOLISIB	APITOLISIB	28389374
8314	BAP1	PROTEASE, TUMOR SUPPRESSOR, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		VALPROIC ACID		22038994
8314	BAP1	PROTEASE, TUMOR SUPPRESSOR, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		SUNITINIB	SUNITINIB	27751729
8314	BAP1	PROTEASE, TUMOR SUPPRESSOR, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		VORINOSTAT	VORINOSTAT	22038994
8314	BAP1	PROTEASE, TUMOR SUPPRESSOR, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		PANOBINOSTAT	PANOBINOSTAT	22038994
8314	BAP1	PROTEASE, TUMOR SUPPRESSOR, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		EVEROLIMUS	EVEROLIMUS	27751729
8314	BAP1	PROTEASE, TUMOR SUPPRESSOR, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		TRICHOSTATIN A		22038994
8314	BAP1	PROTEASE, TUMOR SUPPRESSOR, ENZYME, CLINICALLY ACTIONABLE, DRUG RESISTANCE		OLAPARIB	OLAPARIB	28389374,22683710

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