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: NFIB

Gene summary for NFIB

Gene summary.

Gene information	Species	Human
	Gene symbol	NFIB
	Gene ID	4781
	Gene name	nuclear factor I B
	Gene Alias	CTF
	Cytomap	9p23-p22.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	O00712

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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
4781	NFIB	GSM4909280	Human	Breast	Precancer	4.57e-03	-6.30e-01	0.0305
4781	NFIB	GSM4909281	Human	Breast	IDC	1.03e-24	6.28e-01	0.21
4781	NFIB	GSM4909285	Human	Breast	IDC	4.44e-08	-4.04e-01	0.21
4781	NFIB	GSM4909286	Human	Breast	IDC	1.28e-28	5.83e-01	0.1081
4781	NFIB	GSM4909287	Human	Breast	IDC	1.52e-05	-3.42e-01	0.2057
4781	NFIB	GSM4909290	Human	Breast	IDC	5.30e-10	5.26e-01	0.2096
4781	NFIB	GSM4909291	Human	Breast	IDC	9.42e-03	-3.82e-01	0.1753
4781	NFIB	GSM4909293	Human	Breast	IDC	1.49e-08	3.49e-01	0.1581
4781	NFIB	GSM4909294	Human	Breast	IDC	1.31e-07	-4.41e-01	0.2022
4781	NFIB	GSM4909296	Human	Breast	IDC	1.21e-20	-5.99e-01	0.1524
4781	NFIB	GSM4909297	Human	Breast	IDC	4.77e-29	-6.29e-01	0.1517
4781	NFIB	GSM4909298	Human	Breast	IDC	1.13e-07	2.80e-01	0.1551
4781	NFIB	GSM4909299	Human	Breast	IDC	8.67e-23	6.34e-01	0.035
4781	NFIB	GSM4909301	Human	Breast	IDC	2.84e-05	-3.52e-01	0.1577
4781	NFIB	GSM4909302	Human	Breast	IDC	5.13e-26	-6.01e-01	0.1545
4781	NFIB	GSM4909304	Human	Breast	IDC	2.04e-27	-6.69e-01	0.1636
4781	NFIB	GSM4909306	Human	Breast	IDC	1.37e-05	-3.96e-01	0.1564
4781	NFIB	GSM4909307	Human	Breast	IDC	3.05e-13	-4.58e-01	0.1569
4781	NFIB	GSM4909308	Human	Breast	IDC	3.61e-34	-7.07e-01	0.158
4781	NFIB	GSM4909311	Human	Breast	IDC	1.26e-31	-6.35e-01	0.1534

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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
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:00488578	Breast	Precancer	neural nucleus development	16/1080	64/18723	4.76e-07	2.11e-05	16
GO:00487329	Breast	Precancer	gland development	49/1080	436/18723	6.11e-06	1.73e-04	49
GO:00506736	Breast	Precancer	epithelial cell proliferation	46/1080	437/18723	6.02e-05	1.23e-03	46
GO:00506786	Breast	Precancer	regulation of epithelial cell proliferation	40/1080	381/18723	1.88e-04	3.03e-03	40
GO:00420633	Breast	Precancer	gliogenesis	33/1080	301/18723	3.06e-04	4.40e-03	33
GO:00351486	Breast	Precancer	tube formation	19/1080	148/18723	8.79e-04	1.01e-02	19
GO:00100013	Breast	Precancer	glial cell differentiation	25/1080	225/18723	1.29e-03	1.37e-02	25
GO:00604792	Breast	Precancer	lung cell differentiation	6/1080	24/18723	1.99e-03	1.90e-02	6
GO:004885713	Breast	IDC	neural nucleus development	21/1434	64/18723	5.35e-09	4.28e-07	21
GO:004873214	Breast	IDC	gland development	64/1434	436/18723	3.47e-07	1.74e-05	64
GO:005067313	Breast	IDC	epithelial cell proliferation	60/1434	437/18723	7.13e-06	2.15e-04	60
GO:005067812	Breast	IDC	regulation of epithelial cell proliferation	54/1434	381/18723	8.07e-06	2.39e-04	54
GO:00303244	Breast	IDC	lung development	28/1434	177/18723	1.90e-04	3.15e-03	28
GO:00303234	Breast	IDC	respiratory tube development	28/1434	181/18723	2.78e-04	4.26e-03	28
GO:00605412	Breast	IDC	respiratory system development	30/1434	203/18723	3.85e-04	5.40e-03	30
GO:00226127	Breast	IDC	gland morphogenesis	20/1434	118/18723	6.13e-04	7.69e-03	20
GO:004206311	Breast	IDC	gliogenesis	39/1434	301/18723	8.63e-04	1.00e-02	39
GO:003514812	Breast	IDC	tube formation	23/1434	148/18723	8.79e-04	1.02e-02	23
GO:00104644	Breast	IDC	regulation of mesenchymal cell proliferation	8/1434	28/18723	9.00e-04	1.04e-02	8
GO:00100011	Breast	IDC	glial cell differentiation	31/1434	225/18723	1.04e-03	1.15e-02	31

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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
NFIB	BMEM	Breast	ADJ	FABP4,KRT17,SPARCL1, etc.	3.09e-01
NFIB	NK	Breast	DCIS	FABP4,KRT17,SPARCL1, etc.	1.26e-01
NFIB	BMEM	Breast	Healthy	FABP4,KRT17,SPARCL1, etc.	1.95e-01
NFIB	NK	Breast	Healthy	FABP4,KRT17,SPARCL1, etc.	1.29e-01
NFIB	NK	Breast	IDC	FABP4,KRT17,SPARCL1, etc.	9.71e-02
NFIB	BMEM	Breast	IDC	FABP4,KRT17,SPARCL1, etc.	9.32e-02
NFIB	BMEM	Breast	Precancer	FABP4,KRT17,SPARCL1, etc.	1.83e-01
NFIB	DC	Cervix	CC	ADIRF,C12orf75,SSBP2, etc.	1.08e-01
NFIB	MAIT	Cervix	CC	ADIRF,C12orf75,SSBP2, etc.	6.74e-02
NFIB	BMEM	Cervix	CC	ADIRF,C12orf75,SSBP2, etc.	8.11e-02

∗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

NFIB

SNV

Missense_Mutation

novel

c.580A>C

p.Ser194Arg

p.S194R

O00712

protein_coding

tolerated(0.12)

probably_damaging(0.944)

TCGA-E2-A14V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

NFIB

SNV

Missense_Mutation

c.862G>C

p.Asp288His

p.D288H

O00712

protein_coding

deleterious(0.04)

probably_damaging(0.956)

TCGA-E2-A159-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

NFIB

insertion

Nonsense_Mutation

novel

c.1112_1113insTTTTATATCATTGTATGACCTCTGAAATTTTAGATGCTTTAC

p.Gln371delinsHisPheIleSerLeuTyrAspLeuTerAsnPheArgCysPheThr

p.Q371delinsHFISLYDL*NFRCFT

O00712

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

NFIB

insertion

Frame_Shift_Ins

novel

c.166_167insTTCATTA

p.Ala56ValfsTer7

p.A56Vfs*7

O00712

protein_coding

TCGA-AO-A0J7-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

NFIB

insertion

Nonsense_Mutation

novel

c.165_166insCATAGGGTAGTCTAACAAATATA

p.Ala56HisfsTer5

p.A56Hfs*5

O00712

protein_coding

TCGA-AO-A0J7-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

NFIB

insertion

Frame_Shift_Ins

novel

c.1105_1106insTTTGGGG

p.Pro369LeufsTer41

p.P369Lfs*41

O00712

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NFIB

deletion

Frame_Shift_Del

novel

c.1127delC

p.Pro376GlnfsTer18

p.P376Qfs*18

O00712

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

NFIB

SNV

Missense_Mutation

novel

c.812N>A

p.Arg271Lys

p.R271K

O00712

protein_coding

deleterious(0.01)

probably_damaging(0.92)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NFIB

SNV

Missense_Mutation

novel

c.1270N>A

p.Gly424Arg

p.G424R

O00712

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.979)

TCGA-4J-AA1J-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NFIB

SNV

Missense_Mutation

c.305C>A

p.Pro102Gln

p.P102Q

O00712

protein_coding

deleterious(0.02)

probably_damaging(0.982)

TCGA-C5-A901-01

Cervix

cervical & endocervical cancer

Female

<65

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
4781	NFIB	CLINICALLY ACTIONABLE		methylphenidate	METHYLPHENIDATE	29382897

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