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: NBL1

Gene summary for NBL1

Gene summary.

Gene information	Species	Human
	Gene symbol	NBL1
	Gene ID	4681
	Gene name	NBL1, DAN family BMP antagonist
	Gene Alias	D1S1733E
	Cytomap	1p36.13
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P41271

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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
4681	NBL1	GSM4909282	Human	Breast	IDC	3.63e-35	7.56e-01	-0.0288
4681	NBL1	GSM4909293	Human	Breast	IDC	1.33e-04	2.76e-01	0.1581
4681	NBL1	GSM4909296	Human	Breast	IDC	1.57e-03	-1.01e-01	0.1524
4681	NBL1	GSM4909298	Human	Breast	IDC	1.25e-51	8.65e-01	0.1551
4681	NBL1	GSM4909311	Human	Breast	IDC	7.01e-03	-1.06e-01	0.1534
4681	NBL1	GSM4909321	Human	Breast	IDC	1.48e-02	-1.06e-01	0.1559
4681	NBL1	brca1	Human	Breast	Precancer	2.63e-04	3.24e-01	-0.0338
4681	NBL1	brca2	Human	Breast	Precancer	4.55e-02	1.72e-01	-0.024
4681	NBL1	brca3	Human	Breast	Precancer	2.19e-05	2.09e-01	-0.0263
4681	NBL1	DCIS2	Human	Breast	DCIS	5.19e-09	-1.90e-02	0.0085
4681	NBL1	CA_HPV_3	Human	Cervix	CC	9.22e-27	5.38e-01	0.0414
4681	NBL1	N_HPV_2	Human	Cervix	N_HPV	9.40e-03	2.07e-01	-0.0131
4681	NBL1	Tumor	Human	Cervix	CC	2.96e-22	5.29e-01	0.1241
4681	NBL1	sample3	Human	Cervix	CC	1.12e-23	5.42e-01	0.1387
4681	NBL1	T3	Human	Cervix	CC	1.21e-30	5.54e-01	0.1389
4681	NBL1	HTA11_3410_2000001011	Human	Colorectum	AD	4.44e-13	3.31e-01	0.0155
4681	NBL1	HTA11_2487_2000001011	Human	Colorectum	SER	8.91e-33	1.10e+00	-0.1808
4681	NBL1	HTA11_2951_2000001011	Human	Colorectum	AD	9.08e-03	4.35e-01	0.0216
4681	NBL1	HTA11_1938_2000001011	Human	Colorectum	AD	4.42e-23	8.83e-01	-0.0811
4681	NBL1	HTA11_78_2000001011	Human	Colorectum	AD	8.39e-13	5.33e-01	-0.1088

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00975297	Breast	Precancer	myeloid leukocyte migration	34/1080	220/18723	1.42e-07	7.82e-06	34
GO:00509006	Breast	Precancer	leukocyte migration	47/1080	369/18723	2.82e-07	1.39e-05	47
GO:00305956	Breast	Precancer	leukocyte chemotaxis	34/1080	230/18723	4.16e-07	1.89e-05	34
GO:00603266	Breast	Precancer	cell chemotaxis	41/1080	310/18723	5.99e-07	2.55e-05	41
GO:00451859	Breast	Precancer	maintenance of protein location	19/1080	94/18723	1.43e-06	5.35e-05	19
GO:00512358	Breast	Precancer	maintenance of location	40/1080	327/18723	5.85e-06	1.71e-04	40
GO:00026856	Breast	Precancer	regulation of leukocyte migration	27/1080	210/18723	7.93e-05	1.54e-03	27
GO:00716744	Breast	Precancer	mononuclear cell migration	24/1080	196/18723	4.03e-04	5.44e-03	24
GO:00026887	Breast	Precancer	regulation of leukocyte chemotaxis	17/1080	122/18723	6.34e-04	7.86e-03	17
GO:00026836	Breast	Precancer	negative regulation of immune system process	41/1080	434/18723	1.33e-03	1.40e-02	41
GO:00025483	Breast	Precancer	monocyte chemotaxis	11/1080	70/18723	2.11e-03	2.00e-02	11
GO:00716926	Breast	Precancer	protein localization to extracellular region	34/1080	368/18723	4.65e-03	3.58e-02	34
GO:00509201	Breast	Precancer	regulation of chemotaxis	23/1080	223/18723	5.05e-03	3.80e-02	23
GO:0090025	Breast	Precancer	regulation of monocyte chemotaxis	6/1080	29/18723	5.49e-03	4.01e-02	6
GO:00716754	Breast	Precancer	regulation of mononuclear cell migration	14/1080	115/18723	6.42e-03	4.48e-02	14
GO:005090011	Breast	IDC	leukocyte migration	54/1434	369/18723	3.10e-06	1.15e-04	54
GO:009752911	Breast	IDC	myeloid leukocyte migration	37/1434	220/18723	4.65e-06	1.62e-04	37
GO:003059511	Breast	IDC	leukocyte chemotaxis	38/1434	230/18723	5.36e-06	1.76e-04	38
GO:004518514	Breast	IDC	maintenance of protein location	21/1434	94/18723	6.69e-06	2.05e-04	21
GO:005123513	Breast	IDC	maintenance of location	48/1434	327/18723	9.90e-06	2.77e-04	48

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04350	Colorectum	SER	TGF-beta signaling pathway	31/1580	108/8465	7.00e-03	3.77e-02	2.74e-02	31
hsa043501	Colorectum	SER	TGF-beta signaling pathway	31/1580	108/8465	7.00e-03	3.77e-02	2.74e-02	31
hsa043504	Endometrium	AEH	TGF-beta signaling pathway	26/1197	108/8465	3.82e-03	2.18e-02	1.59e-02	26
hsa0435011	Endometrium	AEH	TGF-beta signaling pathway	26/1197	108/8465	3.82e-03	2.18e-02	1.59e-02	26
hsa043502	Endometrium	EEC	TGF-beta signaling pathway	26/1237	108/8465	5.95e-03	3.12e-02	2.33e-02	26
hsa043503	Endometrium	EEC	TGF-beta signaling pathway	26/1237	108/8465	5.95e-03	3.12e-02	2.33e-02	26
hsa043507	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0435014	Esophagus	ESCC	TGF-beta signaling pathway	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa043506	Oral cavity	OSCC	TGF-beta signaling pathway	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60
hsa0435013	Oral cavity	OSCC	TGF-beta signaling pathway	60/3704	108/8465	8.66e-03	1.97e-02	1.00e-02	60
hsa043505	Prostate	BPH	TGF-beta signaling pathway	35/1718	108/8465	1.98e-03	7.92e-03	4.90e-03	35
hsa0435012	Prostate	BPH	TGF-beta signaling pathway	35/1718	108/8465	1.98e-03	7.92e-03	4.90e-03	35
hsa0435021	Prostate	Tumor	TGF-beta signaling pathway	39/1791	108/8465	2.33e-04	1.35e-03	8.39e-04	39
hsa0435031	Prostate	Tumor	TGF-beta signaling pathway	39/1791	108/8465	2.33e-04	1.35e-03	8.39e-04	39

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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

NBL1

SNV

Missense_Mutation

c.67N>A

p.Gly23Ser

p.G23S

P41271

protein_coding

tolerated_low_confidence(0.34)

benign(0)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NBL1

SNV

Missense_Mutation

novel

c.556N>T

p.His186Tyr

p.H186Y

P41271

protein_coding

tolerated_low_confidence(0.26)

possibly_damaging(0.782)

TCGA-E9-A1R4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

NBL1

SNV

Missense_Mutation

rs765257995

c.211N>A

p.Glu71Lys

p.E71K

P41271

protein_coding

tolerated(0.23)

probably_damaging(0.991)

TCGA-EX-A69L-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NBL1

SNV

Missense_Mutation

c.326N>C

p.Gln109Pro

p.Q109P

P41271

protein_coding

tolerated(0.08)

probably_damaging(0.991)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

NBL1

SNV

Missense_Mutation

rs750974701

c.404C>T

p.Pro135Leu

p.P135L

P41271

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-CM-6164-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

NBL1

SNV

Missense_Mutation

rs765257995

c.211G>A

p.Glu71Lys

p.E71K

P41271

protein_coding

tolerated(0.23)

probably_damaging(0.991)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NBL1

SNV

Missense_Mutation

novel

c.336G>T

p.Glu112Asp

p.E112D

P41271

protein_coding

tolerated(0.38)

probably_damaging(0.986)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

NBL1

SNV

Missense_Mutation

novel

c.193G>T

p.Asp65Tyr

p.D65Y

P41271

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

NBL1

SNV

Missense_Mutation

c.326A>G

p.Gln109Arg

p.Q109R

P41271

protein_coding

deleterious(0.02)

probably_damaging(0.979)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NBL1

SNV

Missense_Mutation

novel

c.484N>T

p.Pro162Ser

p.P162S

P41271

protein_coding

tolerated(0.48)

benign(0.042)

TCGA-DF-A2KU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

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

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