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: BCLAF1

Gene summary for BCLAF1

Gene summary.

Gene information	Species	Human
	Gene symbol	BCLAF1
	Gene ID	9774
	Gene name	BCL2 associated transcription factor 1
	Gene Alias	BTF
	Cytomap	6q23.3
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q9NYF8

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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
9774	BCLAF1	HTA11_3410_2000001011	Human	Colorectum	AD	2.24e-16	-6.36e-01	0.0155
9774	BCLAF1	HTA11_2487_2000001011	Human	Colorectum	SER	3.17e-05	-5.50e-01	-0.1808
9774	BCLAF1	HTA11_3361_2000001011	Human	Colorectum	AD	5.98e-07	-6.38e-01	-0.1207
9774	BCLAF1	HTA11_696_2000001011	Human	Colorectum	AD	4.81e-16	-4.51e-01	-0.1464
9774	BCLAF1	HTA11_866_2000001011	Human	Colorectum	AD	7.98e-16	-5.08e-01	-0.1001
9774	BCLAF1	HTA11_866_3004761011	Human	Colorectum	AD	3.00e-09	-5.58e-01	0.096
9774	BCLAF1	HTA11_9408_2000001011	Human	Colorectum	AD	2.54e-02	-7.12e-01	0.0451
9774	BCLAF1	HTA11_10711_2000001011	Human	Colorectum	AD	4.81e-07	-5.88e-01	0.0338
9774	BCLAF1	HTA11_6818_2000001021	Human	Colorectum	AD	5.12e-04	-5.67e-01	0.0588
9774	BCLAF1	HTA11_99999970781_79442	Human	Colorectum	MSS	2.67e-10	-3.24e-01	0.294
9774	BCLAF1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.31e-02	9.20e-01	0.3487
9774	BCLAF1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.25e-06	-3.65e-01	0.3859
9774	BCLAF1	HTA11_99999974143_84620	Human	Colorectum	MSS	7.53e-14	-4.57e-01	0.3005
9774	BCLAF1	A015-C-203	Human	Colorectum	FAP	4.27e-24	-1.70e-01	-0.1294
9774	BCLAF1	A002-C-201	Human	Colorectum	FAP	3.33e-08	-2.91e-01	0.0324
9774	BCLAF1	A002-C-203	Human	Colorectum	FAP	3.19e-03	-1.10e-01	0.2786
9774	BCLAF1	A001-C-119	Human	Colorectum	FAP	3.51e-02	7.08e-02	-0.1557
9774	BCLAF1	A001-C-108	Human	Colorectum	FAP	2.26e-12	1.32e-01	-0.0272
9774	BCLAF1	A002-C-205	Human	Colorectum	FAP	2.86e-15	-1.78e-03	-0.1236
9774	BCLAF1	A001-C-104	Human	Colorectum	FAP	1.56e-02	7.36e-02	0.0184

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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: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:200123510	Oral cavity	OSCC	positive regulation of apoptotic signaling pathway	92/7305	126/18723	8.45e-15	5.19e-13	92
GO:200102017	Oral cavity	OSCC	regulation of response to DNA damage stimulus	131/7305	219/18723	3.21e-10	8.72e-09	131
GO:20012449	Oral cavity	OSCC	positive regulation of intrinsic apoptotic signaling pathway	44/7305	58/18723	1.22e-08	2.48e-07	44
GO:004362020	Oral cavity	OSCC	regulation of DNA-templated transcription in response to stress	39/7305	53/18723	3.34e-07	5.04e-06	39
GO:20010227	Oral cavity	OSCC	positive regulation of response to DNA damage stimulus	63/7305	105/18723	1.05e-05	1.11e-04	63
GO:00063522	Oral cavity	OSCC	DNA-templated transcription, initiation	74/7305	130/18723	2.56e-05	2.39e-04	74
GO:20001423	Oral cavity	OSCC	regulation of DNA-templated transcription, initiation	26/7305	40/18723	7.79e-04	4.23e-03	26
GO:20001442	Oral cavity	OSCC	positive regulation of DNA-templated transcription, initiation	21/7305	31/18723	1.13e-03	5.75e-03	21
GO:0097193110	Oral cavity	LP	intrinsic apoptotic signaling pathway	146/4623	288/18723	9.76e-22	2.78e-19	146
GO:2001233110	Oral cavity	LP	regulation of apoptotic signaling pathway	168/4623	356/18723	1.35e-20	3.02e-18	168
GO:2001242110	Oral cavity	LP	regulation of intrinsic apoptotic signaling pathway	95/4623	164/18723	9.85e-20	1.99e-17	95
GO:200123518	Oral cavity	LP	positive regulation of apoptotic signaling pathway	63/4623	126/18723	7.17e-10	3.43e-08	63
GO:200124416	Oral cavity	LP	positive regulation of intrinsic apoptotic signaling pathway	33/4623	58/18723	1.63e-07	5.11e-06	33
GO:0043620110	Oral cavity	LP	regulation of DNA-templated transcription in response to stress	28/4623	53/18723	9.88e-06	1.80e-04	28
GO:200102018	Oral cavity	LP	regulation of response to DNA damage stimulus	82/4623	219/18723	1.71e-05	2.97e-04	82
GO:20001441	Oral cavity	LP	positive regulation of DNA-templated transcription, initiation	15/4623	31/18723	3.59e-03	2.39e-02	15
GO:200014211	Oral cavity	LP	regulation of DNA-templated transcription, initiation	18/4623	40/18723	4.00e-03	2.59e-02	18

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
BCLAF1	DUCT1	Pancreas	Healthy	FTX,PNISR,SNHG14, etc.	4.20e-01
BCLAF1	STM	Thyroid	HT	FUS,SFPQ,MT-ATP6, etc.	6.93e-01

∗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

BCLAF1

SNV

Missense_Mutation

c.1967N>T

p.Asp656Val

p.D656V

Q9NYF8

protein_coding

deleterious(0)

possibly_damaging(0.591)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCLAF1

SNV

Missense_Mutation

rs140335385

c.893G>A

p.Arg298Gln

p.R298Q

Q9NYF8

protein_coding

tolerated(0.11)

possibly_damaging(0.492)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCLAF1

SNV

Missense_Mutation

novel

c.265C>T

p.His89Tyr

p.H89Y

Q9NYF8

protein_coding

tolerated_low_confidence(0.28)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCLAF1

SNV

Missense_Mutation

rs771321542

c.704C>A

p.Pro235Gln

p.P235Q

Q9NYF8

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.994)

TCGA-D8-A27M-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

methotrexate+5

BCLAF1

SNV

Missense_Mutation

c.511N>A

p.Gly171Arg

p.G171R

Q9NYF8

protein_coding

deleterious_low_confidence(0)

benign(0.001)

TCGA-GM-A2DF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

BCLAF1

SNV

Missense_Mutation

novel

c.1464N>G

p.Ile488Met

p.I488M

Q9NYF8

protein_coding

tolerated(0.22)

benign(0.169)

TCGA-OL-A66P-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

BCLAF1

insertion

Frame_Shift_Ins

novel

c.172_173insTGTTGGAAATGGATCTAGTCGATACA

p.Arg58LeufsTer19

p.R58Lfs*19

Q9NYF8

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BCLAF1

insertion

Frame_Shift_Ins

novel

c.260_261insGCCAA

p.Tyr88ProfsTer94

p.Y88Pfs*94

Q9NYF8

protein_coding

TCGA-AQ-A04H-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

BCLAF1

deletion

Frame_Shift_Del

novel

c.2056_2057delNN

p.Leu686LysfsTer3

p.L686Kfs*3

Q9NYF8

protein_coding

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

BCLAF1

insertion

Frame_Shift_Ins

novel

c.2055_2056insCGGCC

p.Leu686ArgfsTer3

p.L686Rfs*3

Q9NYF8

protein_coding

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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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