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: BTBD7

Gene summary for BTBD7

Gene summary.

Gene information	Species	Human
	Gene symbol	BTBD7
	Gene ID	55727
	Gene name	BTB domain containing 7
	Gene Alias	FUP1
	Cytomap	14q32.12
	Gene Type	protein-coding
	GO ID	GO:0001763
	UniProtAcc	Q9P203

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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
55727	BTBD7	HTA11_3410_2000001011	Human	Colorectum	AD	3.42e-07	-4.47e-01	0.0155
55727	BTBD7	HTA11_347_2000001011	Human	Colorectum	AD	2.67e-02	3.62e-01	-0.1954
55727	BTBD7	HTA11_99999970781_79442	Human	Colorectum	MSS	1.17e-03	-3.33e-01	0.294
55727	BTBD7	HTA11_99999971662_82457	Human	Colorectum	MSS	9.95e-11	-4.82e-01	0.3859
55727	BTBD7	HTA11_99999974143_84620	Human	Colorectum	MSS	3.49e-13	-5.65e-01	0.3005
55727	BTBD7	F007	Human	Colorectum	FAP	2.31e-02	-3.29e-01	0.1176
55727	BTBD7	A001-C-207	Human	Colorectum	FAP	5.04e-06	-3.96e-01	0.1278
55727	BTBD7	A015-C-203	Human	Colorectum	FAP	1.44e-35	-6.07e-01	-0.1294
55727	BTBD7	A015-C-204	Human	Colorectum	FAP	5.88e-09	-4.13e-01	-0.0228
55727	BTBD7	A014-C-040	Human	Colorectum	FAP	8.76e-05	-4.79e-01	-0.1184
55727	BTBD7	A002-C-201	Human	Colorectum	FAP	5.13e-18	-4.19e-01	0.0324
55727	BTBD7	A002-C-203	Human	Colorectum	FAP	9.05e-08	-2.94e-01	0.2786
55727	BTBD7	A001-C-119	Human	Colorectum	FAP	5.83e-11	-5.70e-01	-0.1557
55727	BTBD7	A001-C-108	Human	Colorectum	FAP	1.56e-18	-4.12e-01	-0.0272
55727	BTBD7	A002-C-205	Human	Colorectum	FAP	4.47e-28	-6.23e-01	-0.1236
55727	BTBD7	A001-C-104	Human	Colorectum	FAP	3.26e-04	-3.94e-01	0.0184
55727	BTBD7	A015-C-005	Human	Colorectum	FAP	2.07e-06	-3.64e-01	-0.0336
55727	BTBD7	A015-C-006	Human	Colorectum	FAP	7.53e-20	-6.28e-01	-0.0994
55727	BTBD7	A015-C-106	Human	Colorectum	FAP	2.73e-21	-4.70e-01	-0.0511
55727	BTBD7	A002-C-114	Human	Colorectum	FAP	9.60e-23	-6.11e-01	-0.1561

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0048732	Colorectum	AD	gland development	149/3918	436/18723	6.07e-11	6.33e-09	149
GO:0022612	Colorectum	AD	gland morphogenesis	42/3918	118/18723	1.62e-04	2.23e-03	42
GO:0001763	Colorectum	AD	morphogenesis of a branching structure	56/3918	196/18723	6.60e-03	4.09e-02	56
GO:00487322	Colorectum	MSS	gland development	143/3467	436/18723	3.85e-13	8.01e-11	143
GO:00226122	Colorectum	MSS	gland morphogenesis	41/3467	118/18723	2.02e-05	4.30e-04	41
GO:00017631	Colorectum	MSS	morphogenesis of a branching structure	55/3467	196/18723	6.70e-04	7.25e-03	55
GO:0061138	Colorectum	MSS	morphogenesis of a branching epithelium	51/3467	182/18723	1.06e-03	1.05e-02	51
GO:00487324	Colorectum	FAP	gland development	103/2622	436/18723	3.61e-08	3.12e-06	103
GO:00226123	Colorectum	FAP	gland morphogenesis	34/2622	118/18723	2.13e-05	5.12e-04	34
GO:00017632	Colorectum	FAP	morphogenesis of a branching structure	44/2622	196/18723	8.79e-04	9.01e-03	44
GO:0060688	Colorectum	FAP	regulation of morphogenesis of a branching structure	15/2622	50/18723	2.68e-03	2.08e-02	15
GO:00611381	Colorectum	FAP	morphogenesis of a branching epithelium	39/2622	182/18723	3.98e-03	2.76e-02	39
GO:00487325	Colorectum	CRC	gland development	88/2078	436/18723	1.62e-08	2.79e-06	88
GO:00226124	Colorectum	CRC	gland morphogenesis	29/2078	118/18723	2.74e-05	7.49e-04	29
GO:00606881	Colorectum	CRC	regulation of morphogenesis of a branching structure	14/2078	50/18723	8.08e-04	1.02e-02	14
GO:00017633	Colorectum	CRC	morphogenesis of a branching structure	36/2078	196/18723	1.64e-03	1.70e-02	36
GO:2000027	Colorectum	CRC	regulation of animal organ morphogenesis	24/2078	125/18723	5.12e-03	3.92e-02	24
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:000020917	Esophagus	ESCC	protein polyubiquitination	170/8552	236/18723	1.40e-16	1.09e-14	170

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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

BTBD7

SNV

Missense_Mutation

novel

c.2414N>A

p.Arg805Lys

p.R805K

Q9P203

protein_coding

tolerated_low_confidence(0.24)

benign(0)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

BTBD7

SNV

Missense_Mutation

c.3331G>A

p.Asp1111Asn

p.D1111N

Q9P203

protein_coding

tolerated_low_confidence(0.08)

benign(0.18)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BTBD7

SNV

Missense_Mutation

rs146101449

c.2072N>A

p.Arg691Gln

p.R691Q

Q9P203

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BTBD7

SNV

Missense_Mutation

c.1853N>G

p.Ala618Gly

p.A618G

Q9P203

protein_coding

tolerated(0.08)

probably_damaging(0.978)

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BTBD7

SNV

Missense_Mutation

c.1462N>C

p.Ser488Arg

p.S488R

Q9P203

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-C8-A12P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

BTBD7

SNV

Missense_Mutation

c.2995N>T

p.Pro999Ser

p.P999S

Q9P203

protein_coding

tolerated_low_confidence(0.12)

benign(0.033)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

BTBD7

insertion

In_Frame_Ins

novel

c.815_816insCTCCCACAAGAATTATATTAG

p.Glu272delinsAspSerHisLysAsnTyrIleArg

p.E272delinsDSHKNYIR

Q9P203

protein_coding

TCGA-A8-A09M-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

BTBD7

SNV

Missense_Mutation

rs61747488

c.1075N>A

p.Ala359Thr

p.A359T

Q9P203

protein_coding

tolerated(0.43)

benign(0.014)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BTBD7

SNV

Missense_Mutation

c.2828N>T

p.Pro943Leu

p.P943L

Q9P203

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.998)

TCGA-EK-A2R7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BTBD7

SNV

Missense_Mutation

c.1765G>C

p.Glu589Gln

p.E589Q

Q9P203

protein_coding

deleterious(0.02)

probably_damaging(0.979)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

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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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