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: SLMAP

Gene summary for SLMAP

Gene summary.

Gene information	Species	Human
	Gene symbol	SLMAP
	Gene ID	7871
	Gene name	sarcolemma associated protein
	Gene Alias	SLAP
	Cytomap	3p14.3
	Gene Type	protein-coding
	GO ID	GO:0001508
	UniProtAcc	Q14BN4

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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
7871	SLMAP	CCI_1	Human	Cervix	CC	1.61e-02	1.12e+00	0.528
7871	SLMAP	CCI_2	Human	Cervix	CC	1.43e-15	1.82e+00	0.5249
7871	SLMAP	CCI_3	Human	Cervix	CC	2.62e-07	8.73e-01	0.516
7871	SLMAP	H2	Human	Cervix	HSIL_HPV	4.12e-03	2.29e-01	0.0632
7871	SLMAP	HTA11_3410_2000001011	Human	Colorectum	AD	7.05e-11	-5.02e-01	0.0155
7871	SLMAP	HTA11_546_2000001011	Human	Colorectum	AD	3.82e-03	-2.62e-01	-0.0842
7871	SLMAP	HTA11_7862_2000001011	Human	Colorectum	AD	8.58e-03	-4.67e-01	-0.0179
7871	SLMAP	HTA11_866_3004761011	Human	Colorectum	AD	3.30e-10	-4.90e-01	0.096
7871	SLMAP	HTA11_4255_2000001011	Human	Colorectum	SER	2.87e-02	-3.26e-01	0.0446
7871	SLMAP	HTA11_7696_3000711011	Human	Colorectum	AD	1.13e-10	-4.02e-01	0.0674
7871	SLMAP	HTA11_6818_2000001021	Human	Colorectum	AD	7.39e-04	-5.05e-01	0.0588
7871	SLMAP	HTA11_99999970781_79442	Human	Colorectum	MSS	4.48e-07	-3.54e-01	0.294
7871	SLMAP	HTA11_99999973899_84307	Human	Colorectum	MSS	2.69e-02	-5.23e-01	0.2585
7871	SLMAP	HTA11_99999974143_84620	Human	Colorectum	MSS	3.74e-19	-5.83e-01	0.3005
7871	SLMAP	F007	Human	Colorectum	FAP	4.18e-02	-2.25e-01	0.1176
7871	SLMAP	A001-C-207	Human	Colorectum	FAP	7.51e-04	-3.09e-01	0.1278
7871	SLMAP	A015-C-203	Human	Colorectum	FAP	2.87e-41	-5.61e-01	-0.1294
7871	SLMAP	A015-C-204	Human	Colorectum	FAP	1.38e-05	-3.43e-01	-0.0228
7871	SLMAP	A014-C-040	Human	Colorectum	FAP	8.18e-07	-5.58e-01	-0.1184
7871	SLMAP	A002-C-201	Human	Colorectum	FAP	5.25e-17	-4.81e-01	0.0324

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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
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:007265910	Cervix	CC	protein localization to plasma membrane	73/2311	284/18723	4.95e-10	6.73e-08	73
GO:19907788	Cervix	CC	protein localization to cell periphery	78/2311	333/18723	1.22e-08	9.73e-07	78
GO:19023059	Cervix	CC	regulation of sodium ion transmembrane transport	19/2311	68/18723	4.21e-04	4.25e-03	19
GO:00020288	Cervix	CC	regulation of sodium ion transport	21/2311	90/18723	2.71e-03	1.85e-02	21
GO:20006498	Cervix	CC	regulation of sodium ion transmembrane transporter activity	15/2311	58/18723	3.75e-03	2.38e-02	15
GO:007265913	Cervix	HSIL_HPV	protein localization to plasma membrane	21/737	284/18723	4.36e-03	3.68e-02	21
GO:0072659	Colorectum	AD	protein localization to plasma membrane	122/3918	284/18723	2.86e-17	1.49e-14	122
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:0002028	Colorectum	AD	regulation of sodium ion transport	36/3918	90/18723	2.89e-05	5.37e-04	36
GO:1902305	Colorectum	AD	regulation of sodium ion transmembrane transport	27/3918	68/18723	3.19e-04	3.80e-03	27
GO:2000649	Colorectum	AD	regulation of sodium ion transmembrane transporter activity	23/3918	58/18723	8.82e-04	8.53e-03	23
GO:00726591	Colorectum	SER	protein localization to plasma membrane	92/2897	284/18723	6.36e-13	1.86e-10	92
GO:19907781	Colorectum	SER	protein localization to cell periphery	98/2897	333/18723	6.09e-11	9.57e-09	98
GO:00020281	Colorectum	SER	regulation of sodium ion transport	28/2897	90/18723	1.45e-04	2.86e-03	28
GO:19023051	Colorectum	SER	regulation of sodium ion transmembrane transport	21/2897	68/18723	1.05e-03	1.22e-02	21
GO:20006491	Colorectum	SER	regulation of sodium ion transmembrane transporter activity	18/2897	58/18723	2.18e-03	2.11e-02	18
GO:0003012	Colorectum	SER	muscle system process	92/2897	452/18723	2.98e-03	2.63e-02	92
GO:0032409	Colorectum	SER	regulation of transporter activity	65/2897	310/18723	5.71e-03	4.19e-02	65
GO:00726592	Colorectum	MSS	protein localization to plasma membrane	113/3467	284/18723	3.23e-17	1.55e-14	113
GO:19907782	Colorectum	MSS	protein localization to cell periphery	120/3467	333/18723	2.02e-14	5.47e-12	120

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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

SLMAP

SNV

Missense_Mutation

c.292C>G

p.Leu98Val

p.L98V

Q14BN4

protein_coding

tolerated(0.11)

benign(0.174)

TCGA-A2-A0CR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SLMAP

SNV

Missense_Mutation

novel

c.2287N>C

p.Glu763Gln

p.E763Q

Q14BN4

protein_coding

deleterious_low_confidence(0.04)

benign(0.103)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SLMAP

SNV

Missense_Mutation

c.1948N>C

p.Glu650Gln

p.E650Q

Q14BN4

protein_coding

deleterious_low_confidence(0.04)

benign(0.164)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLMAP

SNV

Missense_Mutation

c.560N>T

p.Ala187Val

p.A187V

Q14BN4

protein_coding

deleterious(0.04)

probably_damaging(0.954)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SLMAP

SNV

Missense_Mutation

novel

c.487C>G

p.Gln163Glu

p.Q163E

Q14BN4

protein_coding

tolerated(0.16)

probably_damaging(0.986)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SLMAP

SNV

Missense_Mutation

novel

c.1996T>C

p.Trp666Arg

p.W666R

Q14BN4

protein_coding

tolerated_low_confidence(0.25)

benign(0.445)

TCGA-EW-A2FR-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

epirubicin

SLMAP

SNV

Missense_Mutation

rs146606397

c.826N>A

p.Glu276Lys

p.E276K

Q14BN4

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SLMAP

SNV

Missense_Mutation

rs372758327

c.1604N>A

p.Arg535Gln

p.R535Q

Q14BN4

protein_coding

tolerated_low_confidence(0.07)

benign(0.107)

TCGA-S3-A6ZG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

SLMAP

insertion

In_Frame_Ins

novel

c.2388_2389insAAT

p.Asn798dup

p.N798dup

Q14BN4

protein_coding

TCGA-C8-A138-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SLMAP

SNV

Missense_Mutation

rs765688735

c.1508G>A

p.Arg503Gln

p.R503Q

Q14BN4

protein_coding

deleterious_low_confidence(0.01)

benign(0.023)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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