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: BCL2L2

Gene summary for BCL2L2

Gene summary.

Gene information	Species	Human
	Gene symbol	BCL2L2
	Gene ID	599
	Gene name	BCL2 like 2
	Gene Alias	BCL-W
	Cytomap	14q11.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q92843

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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
599	BCL2L2	C04	Human	Oral cavity	OSCC	1.46e-15	5.74e-01	0.2633
599	BCL2L2	C21	Human	Oral cavity	OSCC	1.44e-15	4.77e-01	0.2678
599	BCL2L2	C30	Human	Oral cavity	OSCC	4.14e-24	9.69e-01	0.3055
599	BCL2L2	C43	Human	Oral cavity	OSCC	1.92e-04	1.24e-01	0.1704
599	BCL2L2	C51	Human	Oral cavity	OSCC	1.06e-12	5.70e-01	0.2674
599	BCL2L2	C57	Human	Oral cavity	OSCC	7.81e-04	1.60e-01	0.1679
599	BCL2L2	C08	Human	Oral cavity	OSCC	9.97e-04	1.27e-01	0.1919
599	BCL2L2	SYSMH1	Human	Oral cavity	OSCC	4.60e-04	1.61e-01	0.1127
599	BCL2L2	SYSMH2	Human	Oral cavity	OSCC	2.71e-11	2.16e-01	0.2326
599	BCL2L2	SYSMH3	Human	Oral cavity	OSCC	1.28e-10	2.66e-01	0.2442

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:200123320	Oral cavity	OSCC	regulation of apoptotic signaling pathway	242/7305	356/18723	6.66e-29	3.24e-26	242
GO:009719320	Oral cavity	OSCC	intrinsic apoptotic signaling pathway	202/7305	288/18723	4.64e-27	1.73e-24	202
GO:200124220	Oral cavity	OSCC	regulation of intrinsic apoptotic signaling pathway	123/7305	164/18723	5.71e-21	9.77e-19	123
GO:200123420	Oral cavity	OSCC	negative regulation of apoptotic signaling pathway	148/7305	224/18723	1.71e-16	1.36e-14	148
GO:000683918	Oral cavity	OSCC	mitochondrial transport	162/7305	254/18723	8.96e-16	6.52e-14	162
GO:009719120	Oral cavity	OSCC	extrinsic apoptotic signaling pathway	142/7305	219/18723	7.34e-15	4.55e-13	142
GO:000700610	Oral cavity	OSCC	mitochondrial membrane organization	85/7305	116/18723	6.29e-14	3.40e-12	85
GO:200124320	Oral cavity	OSCC	negative regulation of intrinsic apoptotic signaling pathway	73/7305	98/18723	9.33e-13	4.22e-11	73
GO:000863718	Oral cavity	OSCC	apoptotic mitochondrial changes	78/7305	107/18723	1.06e-12	4.78e-11	78
GO:001082117	Oral cavity	OSCC	regulation of mitochondrion organization	97/7305	144/18723	4.78e-12	1.83e-10	97
GO:000863018	Oral cavity	OSCC	intrinsic apoptotic signaling pathway in response to DNA damage	72/7305	99/18723	9.50e-12	3.50e-10	72
GO:000183616	Oral cavity	OSCC	release of cytochrome c from mitochondria	46/7305	59/18723	1.17e-09	2.87e-08	46
GO:001063918	Oral cavity	OSCC	negative regulation of organelle organization	190/7305	348/18723	2.12e-09	4.97e-08	190
GO:190165316	Oral cavity	OSCC	cellular response to peptide	194/7305	359/18723	4.31e-09	9.57e-08	194
GO:00905598	Oral cavity	OSCC	regulation of membrane permeability	54/7305	78/18723	6.05e-08	1.09e-06	54
GO:00901997	Oral cavity	OSCC	regulation of release of cytochrome c from mitochondria	37/7305	48/18723	8.67e-08	1.52e-06	37
GO:00469028	Oral cavity	OSCC	regulation of mitochondrial membrane permeability	45/7305	63/18723	1.80e-07	2.92e-06	45
GO:006145817	Oral cavity	OSCC	reproductive system development	217/7305	427/18723	3.75e-07	5.63e-06	217
GO:004860816	Oral cavity	OSCC	reproductive structure development	214/7305	424/18723	8.58e-07	1.18e-05	214
GO:00380346	Oral cavity	OSCC	signal transduction in absence of ligand	44/7305	65/18723	2.63e-06	3.26e-05	44

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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

BCL2L2

insertion

Frame_Shift_Ins

novel

c.232_233insCCCTTGTTCTT

p.Arg78ProfsTer24

p.R78Pfs*24

Q92843

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

BCL2L2

insertion

Nonsense_Mutation

novel

c.234_235insCTCTCCCTGTCCAGTGAGTCCTGAGCAT

p.Phe79LeufsTer8

p.F79Lfs*8

Q92843

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

BCL2L2

insertion

Frame_Shift_Ins

novel

c.289_290insCCCGGGGAGGGCCCAGCAGC

p.Val97AlafsTer8

p.V97Afs*8

Q92843

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

BCL2L2

insertion

Frame_Shift_Ins

novel

c.290_291insGACCCGCTGCACCA

p.Ala98ThrfsTer78

p.A98Tfs*78

Q92843

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

BCL2L2

insertion

In_Frame_Ins

novel

c.233_234insTTGTAGGGGTGT

p.Arg78_Phe79insCysArgGlyVal

p.R78_F79insCRGV

Q92843

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

BCL2L2

insertion

In_Frame_Ins

novel

c.234_235insATTGAGCTGACG

p.Arg78_Phe79insIleGluLeuThr

p.R78_F79insIELT

Q92843

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

BCL2L2

deletion

Frame_Shift_Del

c.212_269delNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN

p.Gly73ThrfsTer6

p.G73Tfs*6

Q92843

protein_coding

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

BCL2L2

SNV

Missense_Mutation

rs372109088

c.176N>A

p.Arg59His

p.R59H

Q92843

protein_coding

tolerated(0.06)

benign(0.099)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BCL2L2

SNV

Missense_Mutation

novel

c.556N>A

p.Val186Ile

p.V186I

Q92843

protein_coding

tolerated(0.32)

possibly_damaging(0.739)

TCGA-A6-2672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

BCL2L2

SNV

Missense_Mutation

c.529G>C

p.Ala177Pro

p.A177P

Q92843

protein_coding

deleterious(0.03)

probably_damaging(0.996)

TCGA-A6-5661-01

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
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	NAVITOCLAX	NAVITOCLAX
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	CHEMBL443684	NAVITOCLAX
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		BORTEZOMIB	BORTEZOMIB	15813915
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		2-CDA	CLADRIBINE	15813915
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME	antagonist	252166532	ABT 737
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME	inhibitor	CHEMBL2107358	OBATOCLAX MESYLATE
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		ABT-263	NAVITOCLAX
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME	antagonist	252166530	VENETOCLAX
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		PMID27744724-Compound-18
599	BCL2L2	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		NAVITOCLAX, ABT-263

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