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: SLC25A1

Gene summary for SLC25A1

Gene summary.

Gene information	Species	Human
	Gene symbol	SLC25A1
	Gene ID	6576
	Gene name	solute carrier family 25 member 1
	Gene Alias	CMS23
	Cytomap	22q11.21
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	D9HTE9

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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
6576	SLC25A1	GSM4909281	Human	Breast	IDC	1.23e-04	2.69e-01	0.21
6576	SLC25A1	GSM4909291	Human	Breast	IDC	1.74e-26	7.71e-01	0.1753
6576	SLC25A1	GSM4909304	Human	Breast	IDC	9.75e-27	6.31e-01	0.1636
6576	SLC25A1	GSM4909311	Human	Breast	IDC	3.56e-05	-2.54e-02	0.1534
6576	SLC25A1	GSM4909315	Human	Breast	IDC	4.47e-02	2.69e-01	0.21
6576	SLC25A1	GSM4909317	Human	Breast	IDC	1.78e-16	5.27e-01	0.1355
6576	SLC25A1	GSM4909319	Human	Breast	IDC	3.63e-10	-4.10e-02	0.1563
6576	SLC25A1	GSM4909320	Human	Breast	IDC	9.92e-03	2.70e-01	0.1575
6576	SLC25A1	GSM4909321	Human	Breast	IDC	6.39e-08	2.37e-01	0.1559
6576	SLC25A1	DCIS2	Human	Breast	DCIS	3.71e-40	1.24e-01	0.0085
6576	SLC25A1	HTA11_3410_2000001011	Human	Colorectum	AD	1.67e-08	1.58e-01	0.0155
6576	SLC25A1	HTA11_2487_2000001011	Human	Colorectum	SER	5.17e-22	9.58e-01	-0.1808
6576	SLC25A1	HTA11_1938_2000001011	Human	Colorectum	AD	1.45e-13	4.96e-01	-0.0811
6576	SLC25A1	HTA11_78_2000001011	Human	Colorectum	AD	3.30e-09	4.39e-01	-0.1088
6576	SLC25A1	HTA11_347_2000001011	Human	Colorectum	AD	5.19e-23	5.27e-01	-0.1954
6576	SLC25A1	HTA11_411_2000001011	Human	Colorectum	SER	1.96e-10	1.12e+00	-0.2602
6576	SLC25A1	HTA11_2112_2000001011	Human	Colorectum	SER	1.23e-06	9.45e-01	-0.2196
6576	SLC25A1	HTA11_3361_2000001011	Human	Colorectum	AD	4.70e-09	5.36e-01	-0.1207
6576	SLC25A1	HTA11_83_2000001011	Human	Colorectum	SER	5.90e-10	5.75e-01	-0.1526
6576	SLC25A1	HTA11_696_2000001011	Human	Colorectum	AD	6.77e-27	7.00e-01	-0.1464

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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
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:000683913	Breast	IDC	mitochondrial transport	51/1434	254/18723	1.54e-10	1.83e-08	51
GO:199054214	Breast	IDC	mitochondrial transmembrane transport	25/1434	102/18723	1.39e-07	7.74e-06	25
GO:000915214	Breast	IDC	purine ribonucleotide biosynthetic process	34/1434	169/18723	1.63e-07	8.92e-06	34
GO:004639013	Breast	IDC	ribose phosphate biosynthetic process	36/1434	190/18723	3.40e-07	1.73e-05	36
GO:000926013	Breast	IDC	ribonucleotide biosynthetic process	35/1434	182/18723	3.40e-07	1.73e-05	35
GO:000915014	Breast	IDC	purine ribonucleotide metabolic process	55/1434	368/18723	1.30e-06	5.72e-05	55
GO:001969314	Breast	IDC	ribose phosphate metabolic process	58/1434	396/18723	1.31e-06	5.73e-05	58
GO:000675313	Breast	IDC	nucleoside phosphate metabolic process	68/1434	497/18723	2.01e-06	8.23e-05	68
GO:000911713	Breast	IDC	nucleotide metabolic process	67/1434	489/18723	2.28e-06	9.05e-05	67
GO:000925914	Breast	IDC	ribonucleotide metabolic process	56/1434	385/18723	2.47e-06	9.63e-05	56
GO:000616413	Breast	IDC	purine nucleotide biosynthetic process	34/1434	191/18723	3.11e-06	1.15e-04	34
GO:190129313	Breast	IDC	nucleoside phosphate biosynthetic process	41/1434	256/18723	5.15e-06	1.73e-04	41
GO:000616314	Breast	IDC	purine nucleotide metabolic process	56/1434	396/18723	5.90e-06	1.90e-04	56
GO:007252213	Breast	IDC	purine-containing compound biosynthetic process	34/1434	200/18723	8.79e-06	2.50e-04	34
GO:000916513	Breast	IDC	nucleotide biosynthetic process	40/1434	254/18723	1.01e-05	2.81e-04	40
GO:007252114	Breast	IDC	purine-containing compound metabolic process	57/1434	416/18723	1.28e-05	3.31e-04	57
GO:000683923	Breast	DCIS	mitochondrial transport	51/1390	254/18723	5.04e-11	6.79e-09	51
GO:199054222	Breast	DCIS	mitochondrial transmembrane transport	25/1390	102/18723	7.63e-08	4.45e-06	25
GO:000915223	Breast	DCIS	purine ribonucleotide biosynthetic process	34/1390	169/18723	7.77e-08	4.47e-06	34
GO:004639022	Breast	DCIS	ribose phosphate biosynthetic process	36/1390	190/18723	1.59e-07	8.19e-06	36

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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

SLC25A1

SNV

Missense_Mutation

c.709N>A

p.Gly237Arg

p.G237R

P53007

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C8-A27B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

SLC25A1

SNV

Missense_Mutation

rs782258354

c.694N>A

p.Ala232Thr

p.A232T

P53007

protein_coding

deleterious(0.03)

possibly_damaging(0.846)

TCGA-LL-A7SZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SLC25A1

insertion

Frame_Shift_Ins

novel

c.226_227insTTACCTTCTCACCTATCAGCTGCTTTTACTTTCAGAATTG

p.Arg76LeufsTer26

p.R76Lfs*26

P53007

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

SLC25A1

SNV

Missense_Mutation

c.358G>A

p.Asp120Asn

p.D120N

P53007

protein_coding

tolerated(0.27)

benign(0.007)

TCGA-EX-A1H5-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SLC25A1

SNV

Missense_Mutation

rs431905510

c.845N>A

p.Arg282His

p.R282H

P53007

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-QG-A5Z2-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

SLC25A1

SNV

Missense_Mutation

novel

c.593N>A

p.Arg198His

p.R198H

P53007

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SLC25A1

SNV

Missense_Mutation

novel

c.631N>A

p.Gly211Arg

p.G211R

P53007

protein_coding

deleterious(0.02)

benign(0.445)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SLC25A1

SNV

Missense_Mutation

novel

c.631N>T

p.Gly211Trp

p.G211W

P53007

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AP-A1DM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SLC25A1

SNV

Missense_Mutation

c.457N>A

p.Asp153Asn

p.D153N

P53007

protein_coding

deleterious(0.03)

possibly_damaging(0.709)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

SLC25A1

SNV

Missense_Mutation

novel

c.725N>G

p.Asp242Gly

p.D242G

P53007

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

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
6576	SLC25A1	TRANSPORTER, DRUGGABLE GENOME	inhibitor	178101413

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