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: NASP

Gene summary for NASP

Gene summary.

Gene information	Species	Human
	Gene symbol	NASP
	Gene ID	4678
	Gene name	nuclear autoantigenic sperm protein
	Gene Alias	FLB7527
	Cytomap	1p34.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P49321

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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
4678	NASP	HTA11_1391_2000001011	Human	Colorectum	AD	1.33e-03	4.86e-01	-0.059
4678	NASP	HTA11_99999970781_79442	Human	Colorectum	MSS	2.94e-06	4.24e-01	0.294
4678	NASP	A015-C-203	Human	Colorectum	FAP	4.40e-03	1.11e-01	-0.1294
4678	NASP	A002-C-205	Human	Colorectum	FAP	1.74e-02	2.18e-01	-0.1236
4678	NASP	A015-C-104	Human	Colorectum	FAP	2.15e-04	1.20e-01	-0.1899
4678	NASP	A002-C-016	Human	Colorectum	FAP	3.61e-02	3.13e-02	0.0521
4678	NASP	A002-C-116	Human	Colorectum	FAP	1.84e-04	8.74e-02	-0.0452
4678	NASP	F034	Human	Colorectum	FAP	3.38e-03	2.13e-01	-0.0665
4678	NASP	AEH-subject1	Human	Endometrium	AEH	1.98e-03	1.99e-01	-0.3059
4678	NASP	AEH-subject2	Human	Endometrium	AEH	1.71e-05	-1.17e-01	-0.2525
4678	NASP	AEH-subject3	Human	Endometrium	AEH	5.48e-04	-2.11e-02	-0.2576
4678	NASP	AEH-subject5	Human	Endometrium	AEH	6.85e-05	-2.09e-01	-0.2953
4678	NASP	EEC-subject1	Human	Endometrium	EEC	5.27e-05	-3.62e-02	-0.2682
4678	NASP	EEC-subject3	Human	Endometrium	EEC	3.53e-20	-2.58e-01	-0.2525
4678	NASP	EEC-subject5	Human	Endometrium	EEC	2.13e-02	-2.02e-01	-0.249
4678	NASP	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	7.69e-30	-2.05e-01	-0.1869
4678	NASP	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	4.06e-21	-3.00e-01	-0.1875
4678	NASP	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.94e-28	-2.64e-01	-0.1883
4678	NASP	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	7.07e-24	-1.02e-02	-0.1934
4678	NASP	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	2.11e-42	-2.60e-01	-0.1917

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:00017016	Lung	IAC	in utero embryonic development	68/2061	367/18723	1.12e-05	3.45e-04	68
GO:00448433	Lung	IAC	cell cycle G1/S phase transition	49/2061	241/18723	1.54e-05	4.49e-04	49
GO:19016548	Lung	IAC	response to ketone	39/2061	194/18723	1.40e-04	2.60e-03	39
GO:00063256	Lung	IAC	chromatin organization	69/2061	409/18723	2.01e-04	3.53e-03	69
GO:00335744	Lung	IAC	response to testosterone	11/2061	42/18723	4.72e-03	3.68e-02	11
GO:00447728	Oral cavity	OSCC	mitotic cell cycle phase transition	255/7305	424/18723	5.29e-19	6.98e-17	255
GO:00062603	Oral cavity	OSCC	DNA replication	159/7305	260/18723	3.25e-13	1.59e-11	159
GO:000170116	Oral cavity	OSCC	in utero embryonic development	207/7305	367/18723	7.92e-12	2.95e-10	207
GO:190165419	Oral cavity	OSCC	response to ketone	114/7305	194/18723	1.82e-08	3.60e-07	114
GO:00000826	Oral cavity	OSCC	G1/S transition of mitotic cell cycle	120/7305	214/18723	2.86e-07	4.40e-06	120
GO:006145817	Oral cavity	OSCC	reproductive system development	217/7305	427/18723	3.75e-07	5.63e-06	217
GO:004860816	Oral cavity	OSCC	reproductive structure development	214/7305	424/18723	8.58e-07	1.18e-05	214
GO:00448436	Oral cavity	OSCC	cell cycle G1/S phase transition	131/7305	241/18723	8.77e-07	1.20e-05	131
GO:00018243	Oral cavity	OSCC	blastocyst development	66/7305	106/18723	1.04e-06	1.40e-05	66
GO:0034508	Oral cavity	OSCC	centromere complex assembly	21/7305	30/18723	5.75e-04	3.30e-03	21
GO:00335747	Oral cavity	OSCC	response to testosterone	27/7305	42/18723	8.00e-04	4.29e-03	27
GO:000632510	Oral cavity	OSCC	chromatin organization	190/7305	409/18723	1.17e-03	5.97e-03	190
GO:000170117	Oral cavity	LP	in utero embryonic development	142/4623	367/18723	1.48e-09	6.75e-08	142
GO:004477215	Oral cavity	LP	mitotic cell cycle phase transition	150/4623	424/18723	4.38e-07	1.23e-05	150
GO:1901654110	Oral cavity	LP	response to ketone	78/4623	194/18723	1.24e-06	3.03e-05	78

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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

NASP

SNV

Missense_Mutation

c.1682N>T

p.Ala561Val

p.A561V

P49321

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-B6-A0RM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NASP

SNV

Missense_Mutation

c.1439N>T

p.Ser480Leu

p.S480L

P49321

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-E2-A15S-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NASP

SNV

Missense_Mutation

novel

c.754G>C

p.Glu252Gln

p.E252Q

P49321

protein_coding

deleterious_low_confidence(0)

benign(0.074)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

NASP

deletion

Frame_Shift_Del

c.639delN

p.Gly215GlufsTer52

p.G215Efs*52

P49321

protein_coding

TCGA-BH-A1ES-06

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NASP

SNV

Missense_Mutation

c.325G>A

p.Ala109Thr

p.A109T

P49321

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NASP

SNV

Missense_Mutation

rs201446871

c.970N>A

p.Glu324Lys

p.E324K

P49321

protein_coding

deleterious_low_confidence(0)

benign(0)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

NASP

SNV

Missense_Mutation

c.943N>C

p.Glu315Gln

p.E315Q

P49321

protein_coding

deleterious_low_confidence(0.01)

benign(0.024)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

NASP

SNV

Missense_Mutation

c.1508C>G

p.Ser503Cys

p.S503C

P49321

protein_coding

deleterious(0)

possibly_damaging(0.628)

TCGA-EA-A3HR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NASP

SNV

Missense_Mutation

rs759202853

c.463N>C

p.Glu155Gln

p.E155Q

P49321

protein_coding

deleterious(0.02)

possibly_damaging(0.852)

TCGA-EK-A2R8-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NASP

insertion

Frame_Shift_Ins

novel

c.538_539insCTAAAAATAC

p.Lys180ThrfsTer14

p.K180Tfs*14

P49321

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

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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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