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: SLC25A13

Gene summary for SLC25A13

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC25A13
	Gene ID	10165
	Gene name	solute carrier family 25 member 13
	Gene Alias	ARALAR2
	Cytomap	7q21.3
	Gene Type	protein-coding
	GO ID	GO:0003333
	UniProtAcc	Q9UJS0

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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
10165	SLC25A13	CCI_1	Human	Cervix	CC	1.72e-03	7.30e-01	0.528
10165	SLC25A13	CCI_3	Human	Cervix	CC	4.56e-06	5.80e-01	0.516
10165	SLC25A13	HTA11_3410_2000001011	Human	Colorectum	AD	4.63e-17	-6.04e-01	0.0155
10165	SLC25A13	HTA11_1938_2000001011	Human	Colorectum	AD	3.00e-03	-3.07e-01	-0.0811
10165	SLC25A13	HTA11_696_2000001011	Human	Colorectum	AD	2.49e-04	-3.67e-01	-0.1464
10165	SLC25A13	HTA11_7862_2000001011	Human	Colorectum	AD	2.45e-04	-5.92e-01	-0.0179
10165	SLC25A13	HTA11_866_3004761011	Human	Colorectum	AD	4.00e-05	-4.34e-01	0.096
10165	SLC25A13	HTA11_9408_2000001011	Human	Colorectum	AD	4.89e-02	-8.14e-01	0.0451
10165	SLC25A13	HTA11_10711_2000001011	Human	Colorectum	AD	2.15e-03	-4.52e-01	0.0338
10165	SLC25A13	HTA11_7696_3000711011	Human	Colorectum	AD	5.31e-17	-5.26e-01	0.0674
10165	SLC25A13	HTA11_99999965104_69814	Human	Colorectum	MSS	6.75e-03	4.93e-01	0.281
10165	SLC25A13	HTA11_99999974143_84620	Human	Colorectum	MSS	8.83e-04	-3.79e-01	0.3005
10165	SLC25A13	F007	Human	Colorectum	FAP	1.13e-05	-4.86e-01	0.1176
10165	SLC25A13	A015-C-203	Human	Colorectum	FAP	7.56e-32	-5.51e-01	-0.1294
10165	SLC25A13	A015-C-204	Human	Colorectum	FAP	1.86e-08	-4.68e-01	-0.0228
10165	SLC25A13	A014-C-040	Human	Colorectum	FAP	5.02e-05	-4.88e-01	-0.1184
10165	SLC25A13	A002-C-201	Human	Colorectum	FAP	3.26e-17	-5.17e-01	0.0324
10165	SLC25A13	A001-C-119	Human	Colorectum	FAP	9.42e-06	-4.27e-01	-0.1557
10165	SLC25A13	A001-C-108	Human	Colorectum	FAP	8.29e-20	-4.58e-01	-0.0272
10165	SLC25A13	A002-C-205	Human	Colorectum	FAP	2.57e-23	-5.17e-01	-0.1236

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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
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
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:004603410	Cervix	CC	ATP metabolic process	90/2311	277/18723	7.90e-19	2.36e-15	90
GO:00229049	Cervix	CC	respiratory electron transport chain	42/2311	114/18723	1.67e-11	4.77e-09	42
GO:00453339	Cervix	CC	cellular respiration	66/2311	230/18723	2.07e-11	5.39e-09	66
GO:00229009	Cervix	CC	electron transport chain	53/2311	175/18723	2.23e-10	3.43e-08	53
GO:00060919	Cervix	CC	generation of precursor metabolites and energy	105/2311	490/18723	7.40e-09	6.61e-07	105
GO:00159809	Cervix	CC	energy derivation by oxidation of organic compounds	74/2311	318/18723	3.83e-08	2.53e-06	74
GO:00091449	Cervix	CC	purine nucleoside triphosphate metabolic process	29/2311	88/18723	3.62e-07	1.45e-05	29
GO:00068399	Cervix	CC	mitochondrial transport	60/2311	254/18723	4.21e-07	1.67e-05	60
GO:00092058	Cervix	CC	purine ribonucleoside triphosphate metabolic process	27/2311	82/18723	9.24e-07	3.25e-05	27
GO:00091458	Cervix	CC	purine nucleoside triphosphate biosynthetic process	24/2311	69/18723	1.21e-06	4.15e-05	24
GO:00091998	Cervix	CC	ribonucleoside triphosphate metabolic process	28/2311	89/18723	1.65e-06	5.44e-05	28
GO:00067548	Cervix	CC	ATP biosynthetic process	21/2311	57/18723	1.91e-06	5.97e-05	21
GO:00092068	Cervix	CC	purine ribonucleoside triphosphate biosynthetic process	23/2311	68/18723	3.47e-06	9.26e-05	23
GO:00092018	Cervix	CC	ribonucleoside triphosphate biosynthetic process	24/2311	74/18723	4.95e-06	1.24e-04	24
GO:00091419	Cervix	CC	nucleoside triphosphate metabolic process	31/2311	112/18723	9.38e-06	2.11e-04	31
GO:00091428	Cervix	CC	nucleoside triphosphate biosynthetic process	25/2311	85/18723	2.17e-05	3.89e-04	25
GO:19905428	Cervix	CC	mitochondrial transmembrane transport	26/2311	102/18723	2.10e-04	2.39e-03	26
GO:00196939	Cervix	CC	ribose phosphate metabolic process	72/2311	396/18723	4.49e-04	4.48e-03	72
GO:00092599	Cervix	CC	ribonucleotide metabolic process	70/2311	385/18723	5.35e-04	5.18e-03	70
GO:00463908	Cervix	CC	ribose phosphate biosynthetic process	39/2311	190/18723	9.02e-04	7.77e-03	39

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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

SLC25A13

SNV

Missense_Mutation

rs376257669

c.572N>A

p.Arg191His

p.R191H

Q9UJS0

protein_coding

deleterious(0.02)

benign(0.049)

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

SLC25A13

SNV

Missense_Mutation

c.874N>G

p.Arg292Gly

p.R292G

Q9UJS0

protein_coding

tolerated(0.06)

benign(0.081)

TCGA-A7-A26G-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SLC25A13

SNV

Missense_Mutation

rs142308242

c.874N>T

p.Arg292Trp

p.R292W

Q9UJS0

protein_coding

deleterious(0)

possibly_damaging(0.586)

TCGA-AR-A0TU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Doxorubicin

SLC25A13

SNV

Missense_Mutation

c.1460N>T

p.Ala487Val

p.A487V

Q9UJS0

protein_coding

tolerated(0.06)

probably_damaging(0.933)

TCGA-E2-A1L9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SLC25A13

insertion

Frame_Shift_Ins

novel

c.943_944insTTATGTAC

p.Ser315PhefsTer42

p.S315Ffs*42

Q9UJS0

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC25A13

insertion

Nonsense_Mutation

novel

c.941_942insATATTTCTGAGACTCAGTATTATCAC

p.Ser315TyrfsTer3

p.S315Yfs*3

Q9UJS0

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SLC25A13

SNV

Missense_Mutation

novel

c.690G>A

p.Met230Ile

p.M230I

Q9UJS0

protein_coding

tolerated(0.09)

benign(0.222)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

SLC25A13

SNV

Missense_Mutation

c.871N>A

p.Glu291Lys

p.E291K

Q9UJS0

protein_coding

tolerated(0.08)

benign(0.058)

TCGA-UC-A7PF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SLC25A13

SNV

Missense_Mutation

c.1001G>A

p.Gly334Asp

p.G334D

Q9UJS0

protein_coding

tolerated(0.27)

benign(0.088)

TCGA-A6-3810-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

SLC25A13

SNV

Missense_Mutation

c.2010N>T

p.Lys670Asn

p.K670N

Q9UJS0

protein_coding

tolerated_low_confidence(0.45)

benign(0.01)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

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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