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: NELFB

Gene summary for NELFB

Gene summary.

Gene information	Species	Human
	Gene symbol	NELFB
	Gene ID	25920
	Gene name	negative elongation factor complex member B
	Gene Alias	COBRA1
	Cytomap	9q34.3
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q8WX92

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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
25920	NELFB	LZE7T	Human	Esophagus	ESCC	9.99e-05	1.70e-01	0.0667
25920	NELFB	LZE20T	Human	Esophagus	ESCC	5.70e-11	2.80e-01	0.0662
25920	NELFB	LZE24T	Human	Esophagus	ESCC	1.02e-03	1.03e-01	0.0596
25920	NELFB	P2T-E	Human	Esophagus	ESCC	1.88e-13	1.72e-01	0.1177
25920	NELFB	P4T-E	Human	Esophagus	ESCC	2.22e-14	2.67e-01	0.1323
25920	NELFB	P5T-E	Human	Esophagus	ESCC	4.71e-14	1.42e-01	0.1327
25920	NELFB	P8T-E	Human	Esophagus	ESCC	1.13e-19	3.34e-01	0.0889
25920	NELFB	P9T-E	Human	Esophagus	ESCC	1.62e-03	9.45e-02	0.1131
25920	NELFB	P10T-E	Human	Esophagus	ESCC	3.95e-07	1.54e-01	0.116
25920	NELFB	P11T-E	Human	Esophagus	ESCC	1.04e-06	1.76e-01	0.1426
25920	NELFB	P12T-E	Human	Esophagus	ESCC	6.03e-08	5.57e-02	0.1122
25920	NELFB	P15T-E	Human	Esophagus	ESCC	3.01e-04	1.42e-01	0.1149
25920	NELFB	P16T-E	Human	Esophagus	ESCC	1.84e-03	2.75e-02	0.1153
25920	NELFB	P19T-E	Human	Esophagus	ESCC	3.02e-03	2.21e-01	0.1662
25920	NELFB	P20T-E	Human	Esophagus	ESCC	2.54e-02	2.71e-02	0.1124
25920	NELFB	P21T-E	Human	Esophagus	ESCC	6.03e-16	3.43e-01	0.1617
25920	NELFB	P22T-E	Human	Esophagus	ESCC	1.90e-04	9.58e-02	0.1236
25920	NELFB	P23T-E	Human	Esophagus	ESCC	4.40e-06	1.60e-01	0.108
25920	NELFB	P24T-E	Human	Esophagus	ESCC	1.95e-04	2.27e-01	0.1287
25920	NELFB	P26T-E	Human	Esophagus	ESCC	2.40e-02	8.10e-02	0.1276

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:000635414	Esophagus	ESCC	DNA-templated transcription, elongation	76/8552	91/18723	8.35e-14	4.11e-12	76
GO:000636814	Esophagus	ESCC	transcription elongation from RNA polymerase II promoter	56/8552	69/18723	1.40e-09	3.30e-08	56
GO:003278412	Esophagus	ESCC	regulation of DNA-templated transcription, elongation	45/8552	53/18723	3.64e-09	7.61e-08	45
GO:003424312	Esophagus	ESCC	regulation of transcription elongation from RNA polymerase II promoter	28/8552	32/18723	1.02e-06	1.29e-05	28
GO:00488638	Esophagus	ESCC	stem cell differentiation	122/8552	206/18723	5.95e-05	4.59e-04	122
GO:003424411	Esophagus	ESCC	negative regulation of transcription elongation from RNA polymerase II promoter	14/8552	16/18723	6.78e-04	3.56e-03	14
GO:200073614	Esophagus	ESCC	regulation of stem cell differentiation	39/8552	58/18723	7.43e-04	3.86e-03	39
GO:003278511	Esophagus	ESCC	negative regulation of DNA-templated transcription, elongation	15/8552	18/18723	1.20e-03	5.88e-03	15
GO:200073714	Esophagus	ESCC	negative regulation of stem cell differentiation	17/8552	23/18723	5.73e-03	2.13e-02	17
GO:20007361	Liver	Cirrhotic	regulation of stem cell differentiation	26/4634	58/18723	6.65e-04	5.04e-03	26
GO:20007371	Liver	Cirrhotic	negative regulation of stem cell differentiation	13/4634	23/18723	1.12e-03	7.70e-03	13
GO:00063544	Liver	Cirrhotic	DNA-templated transcription, elongation	35/4634	91/18723	2.56e-03	1.53e-02	35
GO:00063683	Liver	Cirrhotic	transcription elongation from RNA polymerase II promoter	28/4634	69/18723	2.70e-03	1.58e-02	28
GO:004886311	Liver	Cirrhotic	stem cell differentiation	66/4634	206/18723	1.06e-02	4.68e-02	66
GO:000635411	Liver	HCC	DNA-templated transcription, elongation	64/7958	91/18723	7.00e-08	1.44e-06	64
GO:000636811	Liver	HCC	transcription elongation from RNA polymerase II promoter	50/7958	69/18723	4.32e-07	7.22e-06	50
GO:0032784	Liver	HCC	regulation of DNA-templated transcription, elongation	39/7958	53/18723	4.34e-06	5.53e-05	39
GO:0034243	Liver	HCC	regulation of transcription elongation from RNA polymerase II promoter	25/7958	32/18723	4.38e-05	4.26e-04	25
GO:0034244	Liver	HCC	negative regulation of transcription elongation from RNA polymerase II promoter	12/7958	16/18723	8.74e-03	3.40e-02	12
GO:0032785	Liver	HCC	negative regulation of DNA-templated transcription, elongation	13/7958	18/18723	1.05e-02	3.89e-02	13

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa032509	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa0325014	Esophagus	ESCC	Viral life cycle - HIV-1	54/4205	63/8465	2.01e-09	2.17e-08	1.11e-08	54
hsa032502	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa0325011	Liver	HCC	Viral life cycle - HIV-1	46/4020	63/8465	3.25e-05	1.88e-04	1.04e-04	46
hsa032508	Oral cavity	OSCC	Viral life cycle - HIV-1	45/3704	63/8465	7.62e-06	3.59e-05	1.83e-05	45
hsa0325013	Oral cavity	OSCC	Viral life cycle - HIV-1	45/3704	63/8465	7.62e-06	3.59e-05	1.83e-05	45

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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
NELFB	CD4TN	Breast	ADJ	MB21D2,ATP6V1C1,GABPA, etc.	5.34e-02
NELFB	TH17	Breast	DCIS	MB21D2,ATP6V1C1,GABPA, etc.	2.24e-02
NELFB	M2MAC	Breast	DCIS	MB21D2,ATP6V1C1,GABPA, etc.	0.00e+00
NELFB	MON	Breast	DCIS	MB21D2,ATP6V1C1,GABPA, etc.	0.00e+00
NELFB	GC	Breast	Healthy	MB21D2,ATP6V1C1,GABPA, etc.	-4.44e-16
NELFB	TFH	Breast	Healthy	MB21D2,ATP6V1C1,GABPA, etc.	1.63e-02
NELFB	CD8TRM	Breast	IDC	MB21D2,ATP6V1C1,GABPA, etc.	6.82e-04
NELFB	NK	Breast	Precancer	MB21D2,ATP6V1C1,GABPA, etc.	4.38e-02
NELFB	CD8TEX	Breast	Precancer	MB21D2,ATP6V1C1,GABPA, etc.	0.00e+00
NELFB	CD4TN	Breast	Precancer	MB21D2,ATP6V1C1,GABPA, etc.	0.00e+00

∗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

NELFB

SNV

Missense_Mutation

novel

c.1053N>T

p.Met351Ile

p.M351I

protein_coding

deleterious(0.04)

possibly_damaging(0.73)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NELFB

SNV

Missense_Mutation

novel

c.1618N>C

p.Thr540Pro

p.T540P

protein_coding

tolerated(0.28)

benign(0.007)

TCGA-BH-A0BR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NELFB

deletion

In_Frame_Del

c.1507_1521delTTGGCCTTTGGCGAC

p.Leu503_Asp507del

p.L503_D507del

protein_coding

TCGA-A2-A0CM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NELFB

deletion

Frame_Shift_Del

novel

c.1416delN

p.Leu474CysfsTer112

p.L474Cfs*112

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NELFB

SNV

Missense_Mutation

novel

c.1880N>A

p.Pro627Gln

p.P627Q

protein_coding

deleterious_low_confidence(0.03)

benign(0.054)

TCGA-Q1-A73R-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NELFB

SNV

Missense_Mutation

novel

c.1769N>T

p.Ser590Phe

p.S590F

protein_coding

deleterious(0.01)

possibly_damaging(0.546)

TCGA-ZX-AA5X-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

NELFB

SNV

Missense_Mutation

rs755651433

c.1471N>T

p.Arg491Cys

p.R491C

protein_coding

deleterious(0)

possibly_damaging(0.888)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

NELFB

SNV

Missense_Mutation

c.833N>A

p.Arg278Gln

p.R278Q

protein_coding

tolerated(0.05)

benign(0.411)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

NELFB

SNV

Missense_Mutation

rs867374875

c.1562N>T

p.Ala521Val

p.A521V

protein_coding

tolerated(0.19)

benign(0.049)

TCGA-AZ-6601-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

NELFB

SNV

Missense_Mutation

rs760276299

c.827N>A

p.Arg276His

p.R276H

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

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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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