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: SPAG9

Gene summary for SPAG9

Gene summary.

Gene information	Species	Human
	Gene symbol	SPAG9
	Gene ID	9043
	Gene name	sperm associated antigen 9
	Gene Alias	CT89
	Cytomap	17q21.33
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	O60271

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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
9043	SPAG9	CA_HPV_1	Human	Cervix	CC	2.43e-04	3.40e-02	0.0264
9043	SPAG9	CCI_2	Human	Cervix	CC	5.60e-05	1.02e+00	0.5249
9043	SPAG9	AEH-subject1	Human	Endometrium	AEH	5.63e-11	4.29e-01	-0.3059
9043	SPAG9	AEH-subject2	Human	Endometrium	AEH	5.07e-03	2.10e-01	-0.2525
9043	SPAG9	AEH-subject3	Human	Endometrium	AEH	4.51e-02	1.86e-01	-0.2576
9043	SPAG9	AEH-subject4	Human	Endometrium	AEH	7.58e-19	6.15e-01	-0.2657
9043	SPAG9	AEH-subject5	Human	Endometrium	AEH	7.37e-20	6.46e-01	-0.2953
9043	SPAG9	EEC-subject1	Human	Endometrium	EEC	3.24e-12	3.85e-01	-0.2682
9043	SPAG9	EEC-subject2	Human	Endometrium	EEC	8.60e-03	2.40e-01	-0.2607
9043	SPAG9	EEC-subject3	Human	Endometrium	EEC	4.33e-22	4.55e-01	-0.2525
9043	SPAG9	EEC-subject4	Human	Endometrium	EEC	3.09e-11	4.35e-01	-0.2571
9043	SPAG9	EEC-subject5	Human	Endometrium	EEC	4.93e-08	4.37e-01	-0.249
9043	SPAG9	GSM5276934	Human	Endometrium	EEC	1.12e-22	6.56e-01	-0.0913
9043	SPAG9	GSM5276937	Human	Endometrium	EEC	1.25e-47	9.14e-01	-0.0897
9043	SPAG9	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	9.31e-11	-1.33e-01	-0.1869
9043	SPAG9	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	2.44e-08	-1.01e-01	-0.1875
9043	SPAG9	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	1.35e-09	-1.81e-01	-0.1883
9043	SPAG9	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	4.39e-08	-1.97e-01	-0.1934
9043	SPAG9	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	4.88e-16	-5.84e-02	-0.1917
9043	SPAG9	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	2.59e-15	-1.26e-01	-0.1916

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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
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:002260410	Cervix	CC	regulation of cell morphogenesis	84/2311	309/18723	1.00e-12	4.29e-10	84
GO:004593610	Cervix	CC	negative regulation of phosphate metabolic process	88/2311	441/18723	2.92e-06	8.27e-05	88
GO:001056310	Cervix	CC	negative regulation of phosphorus metabolic process	88/2311	442/18723	3.21e-06	8.77e-05	88
GO:004232610	Cervix	CC	negative regulation of phosphorylation	77/2311	385/18723	1.09e-05	2.38e-04	77
GO:00160498	Cervix	CC	cell growth	92/2311	482/18723	1.16e-05	2.49e-04	92
GO:000193310	Cervix	CC	negative regulation of protein phosphorylation	69/2311	342/18723	2.29e-05	4.01e-04	69
GO:00434104	Cervix	CC	positive regulation of MAPK cascade	90/2311	480/18723	2.92e-05	4.83e-04	90
GO:00015588	Cervix	CC	regulation of cell growth	77/2311	414/18723	1.40e-04	1.70e-03	77
GO:00161977	Cervix	CC	endosomal transport	48/2311	230/18723	1.65e-04	1.97e-03	48
GO:00486386	Cervix	CC	regulation of developmental growth	61/2311	330/18723	7.69e-04	6.85e-03	61
GO:00426924	Cervix	CC	muscle cell differentiation	69/2311	384/18723	8.12e-04	7.09e-03	69
GO:00605606	Cervix	CC	developmental growth involved in morphogenesis	46/2311	234/18723	8.82e-04	7.63e-03	46
GO:19901385	Cervix	CC	neuron projection extension	34/2311	172/18723	3.52e-03	2.27e-02	34
GO:00164827	Cervix	CC	cytosolic transport	33/2311	168/18723	4.43e-03	2.70e-02	33
GO:00511464	Cervix	CC	striated muscle cell differentiation	50/2311	283/18723	5.53e-03	3.19e-02	50
GO:00485886	Cervix	CC	developmental cell growth	42/2311	234/18723	7.88e-03	4.15e-02	42
GO:0045665	Cervix	CC	negative regulation of neuron differentiation	16/2311	69/18723	8.75e-03	4.48e-02	16
GO:002260415	Endometrium	AEH	regulation of cell morphogenesis	79/2100	309/18723	1.04e-12	2.24e-10	79
GO:00160499	Endometrium	AEH	cell growth	93/2100	482/18723	1.00e-07	4.99e-06	93
GO:00605607	Endometrium	AEH	developmental growth involved in morphogenesis	53/2100	234/18723	4.02e-07	1.67e-05	53

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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

SPAG9

SNV

Missense_Mutation

c.2055N>A

p.Met685Ile

p.M685I

O60271

protein_coding

deleterious(0)

possibly_damaging(0.829)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPAG9

SNV

Missense_Mutation

c.1695N>G

p.Asn565Lys

p.N565K

O60271

protein_coding

tolerated(0.26)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPAG9

SNV

Missense_Mutation

novel

c.1054N>A

p.Asp352Asn

p.D352N

O60271

protein_coding

deleterious(0)

benign(0.153)

TCGA-BH-A18U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

SPAG9

SNV

Missense_Mutation

c.1414N>C

p.Glu472Gln

p.E472Q

O60271

protein_coding

tolerated(0.11)

probably_damaging(0.986)

TCGA-BH-A209-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SPAG9

SNV

Missense_Mutation

c.1126N>C

p.Asp376His

p.D376H

O60271

protein_coding

deleterious(0.04)

benign(0.365)

TCGA-D8-A147-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine

SPAG9

SNV

Missense_Mutation

novel

c.2686N>A

p.Glu896Lys

p.E896K

O60271

protein_coding

deleterious(0.03)

benign(0.157)

TCGA-E2-A1B1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Other, specify in notesbiphosphonate

zoledronic

SPAG9

SNV

Missense_Mutation

rs764197165

c.2489N>G

p.Asn830Ser

p.N830S

O60271

protein_coding

tolerated(0.77)

benign(0.001)

TCGA-E2-A1IH-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

aromasin

SPAG9

SNV

Missense_Mutation

c.459N>C

p.Lys153Asn

p.K153N

O60271

protein_coding

deleterious(0)

possibly_damaging(0.816)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SPAG9

SNV

Missense_Mutation

c.202G>A

p.Asp68Asn

p.D68N

O60271

protein_coding

tolerated(1)

benign(0)

TCGA-GM-A2DH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

SPAG9

SNV

Missense_Mutation

novel

c.127G>A

p.Asp43Asn

p.D43N

O60271

protein_coding

deleterious(0.01)

probably_damaging(0.99)

TCGA-LL-A5YP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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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