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: BCL2L11

Gene summary for BCL2L11

Gene summary.

Gene information	Species	Human
	Gene symbol	BCL2L11
	Gene ID	10018
	Gene name	BCL2 like 11
	Gene Alias	BAM
	Cytomap	2q13
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	O43521

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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
10018	BCL2L11	LZE4T	Human	Esophagus	ESCC	3.54e-08	6.85e-02	0.0811
10018	BCL2L11	LZE7T	Human	Esophagus	ESCC	2.17e-03	2.85e-01	0.0667
10018	BCL2L11	LZE20T	Human	Esophagus	ESCC	1.42e-03	2.96e-02	0.0662
10018	BCL2L11	LZE24T	Human	Esophagus	ESCC	7.30e-11	3.56e-01	0.0596
10018	BCL2L11	P1T-E	Human	Esophagus	ESCC	1.60e-07	4.35e-01	0.0875
10018	BCL2L11	P2T-E	Human	Esophagus	ESCC	3.35e-09	2.27e-01	0.1177
10018	BCL2L11	P4T-E	Human	Esophagus	ESCC	8.98e-22	6.94e-01	0.1323
10018	BCL2L11	P5T-E	Human	Esophagus	ESCC	5.37e-18	2.83e-02	0.1327
10018	BCL2L11	P8T-E	Human	Esophagus	ESCC	4.11e-13	1.02e-01	0.0889
10018	BCL2L11	P9T-E	Human	Esophagus	ESCC	1.19e-11	3.16e-01	0.1131
10018	BCL2L11	P10T-E	Human	Esophagus	ESCC	5.53e-10	3.33e-01	0.116
10018	BCL2L11	P11T-E	Human	Esophagus	ESCC	1.08e-08	5.96e-01	0.1426
10018	BCL2L11	P12T-E	Human	Esophagus	ESCC	4.65e-11	3.09e-01	0.1122
10018	BCL2L11	P15T-E	Human	Esophagus	ESCC	4.29e-21	5.08e-01	0.1149
10018	BCL2L11	P16T-E	Human	Esophagus	ESCC	3.96e-14	7.49e-02	0.1153
10018	BCL2L11	P20T-E	Human	Esophagus	ESCC	3.32e-05	1.85e-01	0.1124
10018	BCL2L11	P21T-E	Human	Esophagus	ESCC	1.83e-15	2.72e-01	0.1617
10018	BCL2L11	P22T-E	Human	Esophagus	ESCC	1.08e-16	7.51e-04	0.1236
10018	BCL2L11	P23T-E	Human	Esophagus	ESCC	1.23e-17	6.04e-01	0.108
10018	BCL2L11	P24T-E	Human	Esophagus	ESCC	5.90e-09	1.51e-01	0.1287

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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
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:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:0045862111	Esophagus	ESCC	positive regulation of proteolysis	256/8552	372/18723	7.88e-20	9.43e-18	256
GO:0006839110	Esophagus	ESCC	mitochondrial transport	187/8552	254/18723	8.35e-20	9.81e-18	187
GO:001050617	Esophagus	ESCC	regulation of autophagy	220/8552	317/18723	6.72e-18	6.36e-16	220
GO:0035966111	Esophagus	ESCC	response to topologically incorrect protein	125/8552	159/18723	1.44e-17	1.27e-15	125
GO:2001242111	Esophagus	ESCC	regulation of intrinsic apoptotic signaling pathway	128/8552	164/18723	1.75e-17	1.50e-15	128
GO:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:0097191111	Esophagus	ESCC	extrinsic apoptotic signaling pathway	159/8552	219/18723	4.12e-16	2.94e-14	159
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:0006986111	Esophagus	ESCC	response to unfolded protein	107/8552	137/18723	7.01e-15	3.87e-13	107
GO:0031334111	Esophagus	ESCC	positive regulation of protein-containing complex assembly	166/8552	237/18723	2.06e-14	1.07e-12	166
GO:000700619	Esophagus	ESCC	mitochondrial membrane organization	93/8552	116/18723	2.16e-14	1.11e-12	93
GO:00482853	Esophagus	ESCC	organelle fission	301/8552	488/18723	4.64e-13	2.12e-11	301
GO:0035967111	Esophagus	ESCC	cellular response to topologically incorrect protein	90/8552	116/18723	1.94e-12	8.11e-11	90
GO:0010821110	Esophagus	ESCC	regulation of mitochondrion organization	107/8552	144/18723	2.31e-12	9.41e-11	107
GO:0048732111	Esophagus	ESCC	gland development	269/8552	436/18723	7.81e-12	2.95e-10	269

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa05169210	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0421027	Esophagus	ESCC	Apoptosis	102/4205	136/8465	1.05e-09	1.21e-08	6.21e-09	102
hsa0521020	Esophagus	ESCC	Colorectal cancer	69/4205	86/8465	4.06e-09	4.13e-08	2.11e-08	69
hsa040689	Esophagus	ESCC	FoxO signaling pathway	89/4205	131/8465	1.56e-05	7.98e-05	4.09e-05	89
hsa0152110	Esophagus	ESCC	EGFR tyrosine kinase inhibitor resistance	55/4205	79/8465	2.44e-04	8.78e-04	4.50e-04	55
hsa042156	Esophagus	ESCC	Apoptosis - multiple species	25/4205	32/8465	9.13e-04	2.92e-03	1.49e-03	25
hsa041517	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0493238	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0516937	Esophagus	ESCC	Epstein-Barr virus infection	151/4205	202/8465	1.55e-13	3.45e-12	1.77e-12	151
hsa0421037	Esophagus	ESCC	Apoptosis	102/4205	136/8465	1.05e-09	1.21e-08	6.21e-09	102
hsa05210110	Esophagus	ESCC	Colorectal cancer	69/4205	86/8465	4.06e-09	4.13e-08	2.11e-08	69
hsa0406814	Esophagus	ESCC	FoxO signaling pathway	89/4205	131/8465	1.56e-05	7.98e-05	4.09e-05	89
hsa0152115	Esophagus	ESCC	EGFR tyrosine kinase inhibitor resistance	55/4205	79/8465	2.44e-04	8.78e-04	4.50e-04	55
hsa0421511	Esophagus	ESCC	Apoptosis - multiple species	25/4205	32/8465	9.13e-04	2.92e-03	1.49e-03	25
hsa0415114	Esophagus	ESCC	PI3K-Akt signaling pathway	197/4205	354/8465	1.24e-02	2.83e-02	1.45e-02	197
hsa0493228	Oral cavity	OSCC	Non-alcoholic fatty liver disease	124/3704	155/8465	1.22e-20	1.37e-18	6.96e-19	124
hsa0516928	Oral cavity	OSCC	Epstein-Barr virus infection	144/3704	202/8465	1.08e-15	3.60e-14	1.83e-14	144
hsa0421018	Oral cavity	OSCC	Apoptosis	101/3704	136/8465	3.34e-13	7.00e-12	3.56e-12	101
hsa0521018	Oral cavity	OSCC	Colorectal cancer	66/3704	86/8465	3.99e-10	4.95e-09	2.52e-09	66

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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

BCL2L11

SNV

Missense_Mutation

novel

c.184N>A

p.Gly62Ser

p.G62S

O43521

protein_coding

tolerated_low_confidence(0.09)

probably_damaging(0.998)

TCGA-AN-A03Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCL2L11

SNV

Missense_Mutation

c.250A>G

p.Arg84Gly

p.R84G

O43521

protein_coding

deleterious(0.03)

probably_damaging(0.966)

TCGA-AN-A0AT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BCL2L11

SNV

Missense_Mutation

novel

c.151N>A

p.Glu51Lys

p.E51K

O43521

protein_coding

deleterious(0.04)

benign(0.025)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

BCL2L11

SNV

Missense_Mutation

c.458N>C

p.Arg153Pro

p.R153P

O43521

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BCL2L11

SNV

Missense_Mutation

novel

c.587N>C

p.Arg196Thr

p.R196T

O43521

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.966)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

BCL2L11

insertion

Frame_Shift_Ins

novel

c.391_392insAAGGCGGCGCGGCGCGCACCGG

p.Met131LysfsTer15

p.M131Kfs*15

O43521

protein_coding

TCGA-BH-A0GY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyotxan

BCL2L11

insertion

Frame_Shift_Ins

novel

c.393_394insTC

p.Ala132SerfsTer4

p.A132Sfs*4

O43521

protein_coding

TCGA-BH-A0GY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyotxan

BCL2L11

SNV

Missense_Mutation

c.467N>A

p.Gly156Glu

p.G156E

O43521

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EK-A2RO-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BCL2L11

deletion

Frame_Shift_Del

novel

c.479delA

p.Asn160ThrfsTer10

p.N160Tfs*10

O43521

protein_coding

TCGA-C5-A2M2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BCL2L11

insertion

Frame_Shift_Ins

novel

c.551_552insA

p.Arg185ThrfsTer80

p.R185Tfs*80

O43521

protein_coding

TCGA-EA-A5FO-01

Cervix

cervical & endocervical cancer

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
10018	BCL2L11	CLINICALLY ACTIONABLE, DRUG RESISTANCE, TRANSCRIPTION FACTOR		EPIDERMAL GROWTH FACTOR RECEPTOR TYROSINE KINASE INHIBITOR		22426421
10018	BCL2L11	CLINICALLY ACTIONABLE, DRUG RESISTANCE, TRANSCRIPTION FACTOR		imatinib	IMATINIB	24223824
10018	BCL2L11	CLINICALLY ACTIONABLE, DRUG RESISTANCE, TRANSCRIPTION FACTOR		IMATINIB	IMATINIB	22426421
10018	BCL2L11	CLINICALLY ACTIONABLE, DRUG RESISTANCE, TRANSCRIPTION FACTOR		KERACYANIN	KERACYANIN	17360708
10018	BCL2L11	CLINICALLY ACTIONABLE, DRUG RESISTANCE, TRANSCRIPTION FACTOR		corticosteroids		29282361

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