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: BDP1

Gene summary for BDP1

Gene summary.

Gene information	Species	Human
	Gene symbol	BDP1
	Gene ID	55814
	Gene name	B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB
	Gene Alias	DFNB112
	Cytomap	5q13.2
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	A6H8Y1

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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
55814	BDP1	CCI_2	Human	Cervix	CC	4.25e-06	7.85e-01	0.5249
55814	BDP1	CCI_3	Human	Cervix	CC	1.85e-02	5.13e-01	0.516
55814	BDP1	Tumor	Human	Cervix	CC	1.55e-04	-3.08e-01	0.1241
55814	BDP1	sample3	Human	Cervix	CC	4.83e-04	-2.44e-01	0.1387
55814	BDP1	HTA11_3410_2000001011	Human	Colorectum	AD	1.29e-09	-5.38e-01	0.0155
55814	BDP1	HTA11_3361_2000001011	Human	Colorectum	AD	9.48e-03	-5.48e-01	-0.1207
55814	BDP1	HTA11_99999970781_79442	Human	Colorectum	MSS	5.12e-06	-3.83e-01	0.294
55814	BDP1	HTA11_99999971662_82457	Human	Colorectum	MSS	7.12e-04	-3.18e-01	0.3859
55814	BDP1	HTA11_99999974143_84620	Human	Colorectum	MSS	8.16e-07	-4.36e-01	0.3005
55814	BDP1	A002-C-010	Human	Colorectum	FAP	3.57e-04	-6.49e-02	0.242
55814	BDP1	A015-C-203	Human	Colorectum	FAP	1.36e-26	1.26e-01	-0.1294
55814	BDP1	A015-C-204	Human	Colorectum	FAP	4.95e-06	2.25e-01	-0.0228
55814	BDP1	A014-C-040	Human	Colorectum	FAP	3.17e-02	6.32e-02	-0.1184
55814	BDP1	A002-C-201	Human	Colorectum	FAP	4.19e-09	4.87e-02	0.0324
55814	BDP1	A001-C-119	Human	Colorectum	FAP	4.62e-26	6.11e-01	-0.1557
55814	BDP1	A001-C-108	Human	Colorectum	FAP	4.02e-22	3.84e-01	-0.0272
55814	BDP1	A002-C-021	Human	Colorectum	FAP	3.25e-02	3.17e-01	0.1171
55814	BDP1	A002-C-205	Human	Colorectum	FAP	1.57e-40	6.20e-01	-0.1236
55814	BDP1	A014-C-108	Human	Colorectum	FAP	4.62e-06	3.94e-01	-0.124
55814	BDP1	A001-C-104	Human	Colorectum	FAP	1.02e-10	4.22e-01	0.0184

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:00063833	Esophagus	ESCC	transcription by RNA polymerase III	41/8552	46/18723	7.69e-10	1.90e-08	41
GO:000635211	Esophagus	ESCC	DNA-templated transcription, initiation	86/8552	130/18723	1.88e-06	2.19e-05	86
GO:00708973	Esophagus	ESCC	transcription preinitiation complex assembly	30/8552	36/18723	3.60e-06	3.95e-05	30
GO:0070897	Liver	Cirrhotic	transcription preinitiation complex assembly	17/4634	36/18723	2.82e-03	1.63e-02	17
GO:0006352	Liver	HCC	DNA-templated transcription, initiation	78/7958	130/18723	4.19e-05	4.11e-04	78
GO:0006383	Liver	HCC	transcription by RNA polymerase III	31/7958	46/18723	5.67e-04	3.61e-03	31
GO:00708971	Liver	HCC	transcription preinitiation complex assembly	25/7958	36/18723	9.87e-04	5.71e-03	25
GO:00063832	Oral cavity	OSCC	transcription by RNA polymerase III	34/7305	46/18723	1.61e-06	2.11e-05	34
GO:00063522	Oral cavity	OSCC	DNA-templated transcription, initiation	74/7305	130/18723	2.56e-05	2.39e-04	74
GO:00708972	Oral cavity	OSCC	transcription preinitiation complex assembly	24/7305	36/18723	7.18e-04	3.95e-03	24
GO:0071824	Skin	AK	protein-DNA complex subunit organization	38/1910	241/18723	4.43e-03	2.57e-02	38
GO:00063524	Skin	AK	DNA-templated transcription, initiation	23/1910	130/18723	6.10e-03	3.29e-02	23
GO:000635212	Skin	cSCC	DNA-templated transcription, initiation	57/4864	130/18723	7.28e-06	1.01e-04	57
GO:00708974	Skin	cSCC	transcription preinitiation complex assembly	21/4864	36/18723	3.98e-05	4.26e-04	21
GO:00718241	Skin	cSCC	protein-DNA complex subunit organization	87/4864	241/18723	3.09e-04	2.47e-03	87
GO:00063834	Skin	cSCC	transcription by RNA polymerase III	20/4864	46/18723	7.44e-03	3.50e-02	20
GO:00063525	Thyroid	PTC	DNA-templated transcription, initiation	63/5968	130/18723	5.72e-05	5.05e-04	63
GO:00708975	Thyroid	PTC	transcription preinitiation complex assembly	22/5968	36/18723	2.85e-04	2.02e-03	22
GO:00063835	Thyroid	PTC	transcription by RNA polymerase III	23/5968	46/18723	7.89e-03	3.33e-02	23
GO:000635213	Thyroid	ATC	DNA-templated transcription, initiation	64/6293	130/18723	1.60e-04	1.10e-03	64

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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
BDP1	CD8TEXINT	Breast	ADJ	ARGLU1,AKAP9,PBX1, etc.	8.47e-02
BDP1	CD8TEFF	Breast	ADJ	ARGLU1,AKAP9,PBX1, etc.	1.60e-01
BDP1	COL	Cervix	HSIL_HPV	SRRM2,PNN,GOLGB1, etc.	2.66e-01
BDP1	TH1	Colorectum	AD	RHOBTB2,TIMM23B,HERC2, etc.	1.76e-02
BDP1	CD4TN	Colorectum	MSI-H	RHOBTB2,TIMM23B,HERC2, etc.	4.35e-02
BDP1	MAC	Colorectum	MSS	RHOBTB2,TIMM23B,HERC2, etc.	6.43e-02
BDP1	CD8TEFF	Endometrium	ADJ	HAX1,SLC25A20,Z94721.1, etc.	1.64e-02
BDP1	DIFF	Esophagus	Healthy	PPA1,PRSS22,AURKAIP1, etc.	3.56e-02
BDP1	CD8TCM	Oral cavity	ADJ	ARGLU1,GOLGB1,RSRP1, etc.	3.97e-01
BDP1	CD8TCM	Oral cavity	LP	ARGLU1,GOLGB1,RSRP1, etc.	2.37e-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

BDP1

SNV

Missense_Mutation

c.7669N>C

p.Glu2557Gln

p.E2557Q

A6H8Y1

protein_coding

deleterious(0)

possibly_damaging(0.475)

TCGA-A1-A0SH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

BDP1

SNV

Missense_Mutation

c.275N>T

p.Ser92Leu

p.S92L

A6H8Y1

protein_coding

tolerated(0.2)

benign(0.225)

TCGA-A2-A3Y0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

BDP1

SNV

Missense_Mutation

c.560N>A

p.Arg187Lys

p.R187K

A6H8Y1

protein_coding

deleterious(0)

probably_damaging(0.924)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

BDP1

SNV

Missense_Mutation

c.3253N>A

p.Glu1085Lys

p.E1085K

A6H8Y1

protein_coding

tolerated(0.47)

benign(0.014)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BDP1

SNV

Missense_Mutation

rs527435694

c.2661N>C

p.Lys887Asn

p.K887N

A6H8Y1

protein_coding

tolerated(0.13)

benign(0.046)

TCGA-AR-A1AO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

BDP1

SNV

Missense_Mutation

c.1877C>T

p.Ala626Val

p.A626V

A6H8Y1

protein_coding

deleterious(0.01)

probably_damaging(0.947)

TCGA-B6-A0IC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BDP1

SNV

Missense_Mutation

novel

c.6587C>G

p.Ser2196Cys

p.S2196C

A6H8Y1

protein_coding

tolerated(0.06)

benign(0.012)

TCGA-BH-A8FY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BDP1

SNV

Missense_Mutation

c.4178N>G

p.Ser1393Cys

p.S1393C

A6H8Y1

protein_coding

tolerated(0.16)

benign(0.443)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BDP1

SNV

Missense_Mutation

novel

c.6065N>C

p.Ser2022Thr

p.S2022T

A6H8Y1

protein_coding

tolerated(0.27)

possibly_damaging(0.889)

TCGA-D8-A4Z1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

BDP1

SNV

Missense_Mutation

c.7535N>C

p.Cys2512Ser

p.C2512S

A6H8Y1

protein_coding

deleterious(0.05)

probably_damaging(0.999)

TCGA-GM-A2DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

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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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