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: NUP98

Gene summary for NUP98

Gene summary.

Gene information	Species	Human
	Gene symbol	NUP98
	Gene ID	4928
	Gene name	nucleoporin 98 and 96 precursor
	Gene Alias	ADIR2
	Cytomap	11p15.4
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	P52948

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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
4928	NUP98	AEH-subject1	Human	Endometrium	AEH	5.56e-06	4.05e-01	-0.3059
4928	NUP98	AEH-subject4	Human	Endometrium	AEH	4.63e-02	3.32e-01	-0.2657
4928	NUP98	AEH-subject5	Human	Endometrium	AEH	5.62e-09	4.24e-01	-0.2953
4928	NUP98	EEC-subject1	Human	Endometrium	EEC	4.34e-09	4.54e-01	-0.2682
4928	NUP98	EEC-subject4	Human	Endometrium	EEC	3.68e-05	4.01e-01	-0.2571
4928	NUP98	EEC-subject5	Human	Endometrium	EEC	4.60e-02	2.67e-01	-0.249
4928	NUP98	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.53e-03	4.11e-02	-0.1869
4928	NUP98	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	6.60e-05	-3.79e-03	-0.1875
4928	NUP98	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	2.56e-08	-2.65e-02	-0.1883
4928	NUP98	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	2.30e-02	-1.92e-02	-0.1934
4928	NUP98	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	2.28e-05	-9.68e-02	-0.1917
4928	NUP98	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	1.70e-11	-4.42e-02	-0.1916
4928	NUP98	LZE2T	Human	Esophagus	ESCC	6.79e-03	2.41e-01	0.082
4928	NUP98	LZE4T	Human	Esophagus	ESCC	1.44e-11	1.52e-01	0.0811
4928	NUP98	LZE7T	Human	Esophagus	ESCC	6.50e-11	5.88e-01	0.0667
4928	NUP98	LZE8T	Human	Esophagus	ESCC	5.85e-07	3.24e-01	0.067
4928	NUP98	LZE22D1	Human	Esophagus	HGIN	3.52e-02	4.53e-02	0.0595
4928	NUP98	LZE22T	Human	Esophagus	ESCC	1.09e-02	1.34e-01	0.068
4928	NUP98	LZE24T	Human	Esophagus	ESCC	1.31e-18	5.10e-01	0.0596
4928	NUP98	LZE21T	Human	Esophagus	ESCC	1.31e-09	3.73e-01	0.0655

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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

∗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:005116931	Oral cavity	NEOLP	nuclear transport	75/2005	301/18723	1.56e-12	3.20e-10	75
GO:003450432	Oral cavity	NEOLP	protein localization to nucleus	71/2005	290/18723	1.49e-11	2.21e-09	71
GO:003312032	Oral cavity	NEOLP	positive regulation of RNA splicing	19/2005	37/18723	8.91e-10	6.61e-08	19
GO:000640331	Oral cavity	NEOLP	RNA localization	50/2005	201/18723	8.49e-09	4.39e-07	50
GO:190331331	Oral cavity	NEOLP	positive regulation of mRNA metabolic process	35/2005	118/18723	1.25e-08	5.94e-07	35
GO:007259432	Oral cavity	NEOLP	establishment of protein localization to organelle	84/2005	422/18723	1.30e-08	6.10e-07	84
GO:005065731	Oral cavity	NEOLP	nucleic acid transport	40/2005	163/18723	3.74e-07	1.15e-05	40
GO:005065831	Oral cavity	NEOLP	RNA transport	40/2005	163/18723	3.74e-07	1.15e-05	40
GO:005123631	Oral cavity	NEOLP	establishment of RNA localization	40/2005	166/18723	6.24e-07	1.82e-05	40
GO:001593131	Oral cavity	NEOLP	nucleobase-containing compound transport	48/2005	222/18723	1.51e-06	3.77e-05	48
GO:004802632	Oral cavity	NEOLP	positive regulation of mRNA splicing, via spliceosome	11/2005	22/18723	4.74e-06	1.01e-04	11
GO:005068531	Oral cavity	NEOLP	positive regulation of mRNA processing	13/2005	32/18723	1.14e-05	2.10e-04	13
GO:005102831	Oral cavity	NEOLP	mRNA transport	31/2005	130/18723	1.38e-05	2.43e-04	31
GO:005117031	Oral cavity	NEOLP	import into nucleus	35/2005	159/18723	2.54e-05	3.99e-04	35
GO:001703831	Oral cavity	NEOLP	protein import	42/2005	206/18723	2.98e-05	4.54e-04	42
GO:000660631	Oral cavity	NEOLP	protein import into nucleus	34/2005	155/18723	3.55e-05	5.20e-04	34
GO:004693113	Oral cavity	NEOLP	pore complex assembly	8/2005	20/18723	6.57e-04	5.51e-03	8
GO:00069973	Oral cavity	NEOLP	nucleus organization	27/2005	133/18723	7.89e-04	6.27e-03	27
GO:00069992	Oral cavity	NEOLP	nuclear pore organization	6/2005	14/18723	2.10e-03	1.38e-02	6
GO:190331116	Prostate	BPH	regulation of mRNA metabolic process	111/3107	288/18723	2.28e-19	1.17e-16	111

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501420	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123
hsa05014110	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123
hsa0501425	Endometrium	EEC	Amyotrophic lateral sclerosis	128/1237	364/8465	9.83e-24	4.04e-22	3.01e-22	128
hsa0501435	Endometrium	EEC	Amyotrophic lateral sclerosis	128/1237	364/8465	9.83e-24	4.04e-22	3.01e-22	128
hsa0501430	Esophagus	HGIN	Amyotrophic lateral sclerosis	140/1383	364/8465	2.13e-25	1.16e-23	9.19e-24	140
hsa030137	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa0516420	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa05014113	Esophagus	HGIN	Amyotrophic lateral sclerosis	140/1383	364/8465	2.13e-25	1.16e-23	9.19e-24	140
hsa0301312	Esophagus	HGIN	Nucleocytoplasmic transport	31/1383	108/8465	8.29e-04	7.95e-03	6.31e-03	31
hsa05164110	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa05014210	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0501438	Esophagus	ESCC	Amyotrophic lateral sclerosis	266/4205	364/8465	1.31e-20	2.20e-18	1.13e-18	266
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0501414	Liver	Cirrhotic	Amyotrophic lateral sclerosis	187/2530	364/8465	1.56e-18	6.50e-17	4.01e-17	187
hsa0516410	Liver	Cirrhotic	Influenza A	66/2530	171/8465	8.56e-03	2.91e-02	1.79e-02	66
hsa0501415	Liver	Cirrhotic	Amyotrophic lateral sclerosis	187/2530	364/8465	1.56e-18	6.50e-17	4.01e-17	187
hsa0516411	Liver	Cirrhotic	Influenza A	66/2530	171/8465	8.56e-03	2.91e-02	1.79e-02	66

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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

NUP98

SNV

Missense_Mutation

novel

c.4906C>A

p.His1636Asn

p.H1636N

P52948

protein_coding

tolerated(0.08)

probably_damaging(0.958)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

NUP98

SNV

Missense_Mutation

c.410N>G

p.Ser137Cys

p.S137C

P52948

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

NUP98

SNV

Missense_Mutation

c.2317G>A

p.Asp773Asn

p.D773N

P52948

protein_coding

deleterious(0)

benign(0.103)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

NUP98

SNV

Missense_Mutation

c.4660N>T

p.His1554Tyr

p.H1554Y

P52948

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP98

SNV

Missense_Mutation

c.4966G>A

p.Asp1656Asn

p.D1656N

P52948

protein_coding

tolerated(0.3)

possibly_damaging(0.862)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP98

SNV

Missense_Mutation

c.1211G>A

p.Gly404Glu

p.G404E

P52948

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP98

SNV

Missense_Mutation

novel

c.988N>A

p.Leu330Ile

p.L330I

P52948

protein_coding

tolerated(0.16)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP98

SNV

Missense_Mutation

rs752419423

c.3307N>T

p.Arg1103Cys

p.R1103C

P52948

protein_coding

deleterious(0.02)

benign(0.398)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NUP98

SNV

Missense_Mutation

novel

c.3459G>T

p.Gln1153His

p.Q1153H

P52948

protein_coding

tolerated(0.08)

benign(0.001)

TCGA-AR-A2LL-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

NUP98

SNV

Missense_Mutation

c.4571N>T

p.Ser1524Leu

p.S1524L

P52948

protein_coding

tolerated(0.07)

benign(0.202)

TCGA-BH-A18J-01

Breast

breast invasive carcinoma

Female

<65

III/IV

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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