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: NEBL

Gene summary for NEBL

Gene summary.

Gene information	Species	Human
	Gene symbol	NEBL
	Gene ID	10529
	Gene name	nebulette
	Gene Alias	C10orf113
	Cytomap	10p12.31
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	O76041

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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
10529	NEBL	N_HPV_1	Human	Cervix	N_HPV	1.61e-02	-9.93e-02	0.0079
10529	NEBL	CCI_1	Human	Cervix	CC	2.59e-20	1.64e+00	0.528
10529	NEBL	CCI_2	Human	Cervix	CC	3.96e-06	1.64e+00	0.5249
10529	NEBL	CCI_3	Human	Cervix	CC	1.32e-14	1.29e+00	0.516
10529	NEBL	sample3	Human	Cervix	CC	8.53e-03	1.67e-01	0.1387
10529	NEBL	T1	Human	Cervix	CC	8.81e-07	3.38e-01	0.0918
10529	NEBL	HTA11_3410_2000001011	Human	Colorectum	AD	8.15e-03	-2.04e-01	0.0155
10529	NEBL	HTA11_2487_2000001011	Human	Colorectum	SER	1.65e-02	-4.08e-01	-0.1808
10529	NEBL	HTA11_1391_2000001011	Human	Colorectum	AD	4.48e-02	6.83e-01	-0.059
10529	NEBL	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.27e-12	1.38e+00	0.3487
10529	NEBL	HTA11_99999965104_69814	Human	Colorectum	MSS	4.75e-06	7.36e-01	0.281
10529	NEBL	HTA11_99999971662_82457	Human	Colorectum	MSS	9.35e-07	8.31e-01	0.3859
10529	NEBL	F007	Human	Colorectum	FAP	3.42e-03	4.27e-01	0.1176
10529	NEBL	A002-C-010	Human	Colorectum	FAP	5.66e-13	4.97e-01	0.242
10529	NEBL	A001-C-207	Human	Colorectum	FAP	8.70e-08	5.16e-01	0.1278
10529	NEBL	A015-C-203	Human	Colorectum	FAP	5.58e-21	5.66e-02	-0.1294
10529	NEBL	A002-C-201	Human	Colorectum	FAP	3.26e-06	8.85e-02	0.0324
10529	NEBL	A002-C-203	Human	Colorectum	FAP	6.05e-11	5.07e-01	0.2786
10529	NEBL	A001-C-108	Human	Colorectum	FAP	4.80e-14	4.41e-01	-0.0272
10529	NEBL	A002-C-021	Human	Colorectum	FAP	4.96e-20	6.03e-01	0.1171

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:00605375	Cervix	CC	muscle tissue development	76/2311	403/18723	9.76e-05	1.27e-03	76
GO:00310329	Cervix	CC	actomyosin structure organization	43/2311	196/18723	1.11e-04	1.40e-03	43
GO:00147064	Cervix	CC	striated muscle tissue development	72/2311	384/18723	1.76e-04	2.07e-03	72
GO:00426924	Cervix	CC	muscle cell differentiation	69/2311	384/18723	8.12e-04	7.09e-03	69
GO:00511464	Cervix	CC	striated muscle cell differentiation	50/2311	283/18723	5.53e-03	3.19e-02	50
GO:000701525	Cervix	N_HPV	actin filament organization	29/534	442/18723	3.00e-05	8.02e-04	29
GO:006053722	Cervix	N_HPV	muscle tissue development	21/534	403/18723	6.10e-03	4.21e-02	21
GO:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0031032	Colorectum	AD	actomyosin structure organization	65/3918	196/18723	4.17e-05	7.37e-04	65
GO:00070151	Colorectum	SER	actin filament organization	134/2897	442/18723	1.39e-15	5.70e-13	134
GO:00310321	Colorectum	SER	actomyosin structure organization	45/2897	196/18723	3.60e-03	3.03e-02	45
GO:00070152	Colorectum	MSS	actin filament organization	146/3467	442/18723	1.16e-13	2.67e-11	146
GO:00310322	Colorectum	MSS	actomyosin structure organization	53/3467	196/18723	2.04e-03	1.75e-02	53
GO:00070153	Colorectum	MSI-H	actin filament organization	50/1319	442/18723	6.19e-04	1.21e-02	50
GO:00070154	Colorectum	FAP	actin filament organization	125/2622	442/18723	1.97e-15	3.03e-12	125
GO:00310323	Colorectum	FAP	actomyosin structure organization	51/2622	196/18723	5.89e-06	1.88e-04	51
GO:0055006	Colorectum	FAP	cardiac cell development	22/2622	91/18723	6.44e-03	4.01e-02	22
GO:00070155	Colorectum	CRC	actin filament organization	104/2078	442/18723	4.75e-14	7.12e-11	104
GO:00310324	Colorectum	CRC	actomyosin structure organization	45/2078	196/18723	1.49e-06	8.14e-05	45

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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

NEBL

SNV

Missense_Mutation

c.842C>T

p.Ser281Leu

p.S281L

O76041

protein_coding

deleterious(0.01)

benign(0.143)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NEBL

SNV

Missense_Mutation

c.54N>G

p.Ile18Met

p.I18M

O76041

protein_coding

tolerated_low_confidence(0.12)

benign(0.066)

TCGA-AN-A0AM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NEBL

SNV

Missense_Mutation

c.584N>A

p.Ala195Glu

p.A195E

O76041

protein_coding

deleterious(0)

possibly_damaging(0.806)

TCGA-BH-A0BP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NEBL

SNV

Missense_Mutation

c.1138G>C

p.Glu380Gln

p.E380Q

O76041

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NEBL

SNV

Missense_Mutation

c.40G>A

p.Glu14Lys

p.E14K

O76041

protein_coding

tolerated_low_confidence(0.12)

possibly_damaging(0.893)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

NEBL

SNV

Missense_Mutation

novel

c.316N>G

p.Pro106Ala

p.P106A

O76041

protein_coding

tolerated(0.08)

possibly_damaging(0.517)

TCGA-D8-A13Z-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

NEBL

insertion

Frame_Shift_Ins

novel

c.2182_2183insTGAATCGTTGTTTAAATGAATATAATTTTAACCTAAG

p.Thr728MetfsTer19

p.T728Mfs*19

O76041

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NEBL

SNV

Missense_Mutation

novel

c.1131N>T

p.Glu377Asp

p.E377D

O76041

protein_coding

deleterious(0)

benign(0.088)

TCGA-VS-A9UJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NEBL

SNV

Missense_Mutation

c.272N>C

p.Gly91Ala

p.G91A

O76041

protein_coding

tolerated(0.33)

benign(0.009)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

NEBL

SNV

Missense_Mutation

c.1115A>G

p.Glu372Gly

p.E372G

O76041

protein_coding

tolerated(0.26)

possibly_damaging(0.626)

TCGA-AD-6964-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folfox

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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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