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: ALDH18A1

Gene summary for ALDH18A1

Gene summary.

Gene information	Species	Human
	Gene symbol	ALDH18A1
	Gene ID	5832
	Gene name	aldehyde dehydrogenase 18 family member A1
	Gene Alias	ADCL3
	Cytomap	10q24.1
	Gene Type	protein-coding
	GO ID	GO:0000052
	UniProtAcc	P54886

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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
5832	ALDH18A1	HTA11_2487_2000001011	Human	Colorectum	SER	1.81e-02	3.76e-01	-0.1808
5832	ALDH18A1	HTA11_1938_2000001011	Human	Colorectum	AD	6.93e-05	6.66e-01	-0.0811
5832	ALDH18A1	HTA11_347_2000001011	Human	Colorectum	AD	5.67e-10	6.22e-01	-0.1954
5832	ALDH18A1	HTA11_1391_2000001011	Human	Colorectum	AD	9.79e-05	5.62e-01	-0.059
5832	ALDH18A1	HTA11_99999965104_69814	Human	Colorectum	MSS	4.44e-05	6.45e-01	0.281
5832	ALDH18A1	HTA11_99999971662_82457	Human	Colorectum	MSS	3.97e-14	8.23e-01	0.3859
5832	ALDH18A1	A015-C-203	Human	Colorectum	FAP	1.49e-11	-1.55e-01	-0.1294
5832	ALDH18A1	A002-C-201	Human	Colorectum	FAP	2.08e-06	-2.00e-01	0.0324
5832	ALDH18A1	A001-C-119	Human	Colorectum	FAP	1.40e-05	-3.45e-01	-0.1557
5832	ALDH18A1	A001-C-108	Human	Colorectum	FAP	8.30e-07	-2.08e-01	-0.0272
5832	ALDH18A1	A002-C-205	Human	Colorectum	FAP	1.15e-12	-2.73e-01	-0.1236
5832	ALDH18A1	A015-C-005	Human	Colorectum	FAP	7.99e-03	-1.78e-01	-0.0336
5832	ALDH18A1	A015-C-006	Human	Colorectum	FAP	3.82e-07	-2.44e-01	-0.0994
5832	ALDH18A1	A015-C-106	Human	Colorectum	FAP	5.43e-04	-1.75e-01	-0.0511
5832	ALDH18A1	A002-C-114	Human	Colorectum	FAP	2.42e-10	-3.10e-01	-0.1561
5832	ALDH18A1	A015-C-104	Human	Colorectum	FAP	6.50e-16	-3.04e-01	-0.1899
5832	ALDH18A1	A001-C-014	Human	Colorectum	FAP	4.55e-07	-2.00e-01	0.0135
5832	ALDH18A1	A002-C-016	Human	Colorectum	FAP	1.59e-10	-2.12e-01	0.0521
5832	ALDH18A1	A015-C-002	Human	Colorectum	FAP	6.03e-07	-3.20e-01	-0.0763
5832	ALDH18A1	A001-C-203	Human	Colorectum	FAP	2.73e-03	-9.15e-02	-0.0481

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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
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
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:0043648	Colorectum	AD	dicarboxylic acid metabolic process	34/3918	96/18723	7.22e-04	7.28e-03	34
GO:0006520	Colorectum	AD	cellular amino acid metabolic process	81/3918	284/18723	1.37e-03	1.19e-02	81
GO:00065201	Colorectum	SER	cellular amino acid metabolic process	61/2897	284/18723	4.20e-03	3.41e-02	61
GO:0046394	Colorectum	MSS	carboxylic acid biosynthetic process	76/3467	314/18723	6.71e-03	4.38e-02	76
GO:0016053	Colorectum	MSS	organic acid biosynthetic process	76/3467	316/18723	7.88e-03	4.84e-02	76
GO:00436481	Colorectum	FAP	dicarboxylic acid metabolic process	24/2622	96/18723	2.88e-03	2.20e-02	24
GO:00086525	Esophagus	ESCC	cellular amino acid biosynthetic process	51/8552	76/18723	1.30e-04	8.88e-04	51
GO:00463948	Esophagus	ESCC	carboxylic acid biosynthetic process	175/8552	314/18723	1.98e-04	1.26e-03	175
GO:00160538	Esophagus	ESCC	organic acid biosynthetic process	175/8552	316/18723	3.04e-04	1.82e-03	175
GO:19016075	Esophagus	ESCC	alpha-amino acid biosynthetic process	45/8552	68/18723	5.13e-04	2.84e-03	45
GO:00436485	Esophagus	ESCC	dicarboxylic acid metabolic process	58/8552	96/18723	2.55e-03	1.09e-02	58
GO:001605321	Liver	HCC	organic acid biosynthetic process	200/7958	316/18723	5.24e-14	3.22e-12	200
GO:004639421	Liver	HCC	carboxylic acid biosynthetic process	198/7958	314/18723	1.19e-13	6.78e-12	198
GO:00086522	Liver	HCC	cellular amino acid biosynthetic process	58/7958	76/18723	1.98e-09	5.63e-08	58
GO:19016052	Liver	HCC	alpha-amino acid metabolic process	124/7958	195/18723	2.07e-09	5.79e-08	124
GO:19016072	Liver	HCC	alpha-amino acid biosynthetic process	53/7958	68/18723	2.62e-09	7.16e-08	53
GO:00436482	Liver	HCC	dicarboxylic acid metabolic process	68/7958	96/18723	1.73e-08	4.14e-07	68
GO:00065202	Liver	HCC	cellular amino acid metabolic process	167/7958	284/18723	1.91e-08	4.56e-07	167
GO:0009064	Liver	HCC	glutamine family amino acid metabolic process	47/7958	78/18723	1.17e-03	6.54e-03	47
GO:0006536	Liver	HCC	glutamate metabolic process	21/7958	33/18723	1.16e-02	4.28e-02	21

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00330	Colorectum	AD	Arginine and proline metabolism	23/2092	50/8465	8.27e-04	5.90e-03	3.76e-03	23
hsa01230	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa003301	Colorectum	AD	Arginine and proline metabolism	23/2092	50/8465	8.27e-04	5.90e-03	3.76e-03	23
hsa012301	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa012302	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
hsa012303	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
hsa003304	Colorectum	MSS	Arginine and proline metabolism	23/1875	50/8465	1.52e-04	1.24e-03	7.61e-04	23
hsa003305	Colorectum	MSS	Arginine and proline metabolism	23/1875	50/8465	1.52e-04	1.24e-03	7.61e-04	23
hsa003306	Colorectum	FAP	Arginine and proline metabolism	16/1404	50/8465	5.33e-03	2.10e-02	1.27e-02	16
hsa003307	Colorectum	FAP	Arginine and proline metabolism	16/1404	50/8465	5.33e-03	2.10e-02	1.27e-02	16
hsa0123023	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0123033	Esophagus	ESCC	Biosynthesis of amino acids	49/4205	75/8465	4.35e-03	1.12e-02	5.74e-03	49
hsa0123021	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa0033021	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa0123031	Liver	HCC	Biosynthesis of amino acids	53/4020	75/8465	3.79e-05	2.11e-04	1.18e-04	53
hsa0033031	Liver	HCC	Arginine and proline metabolism	33/4020	50/8465	6.28e-03	1.77e-02	9.83e-03	33
hsa012305	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0123012	Oral cavity	OSCC	Biosynthesis of amino acids	45/3704	75/8465	3.27e-03	8.23e-03	4.19e-03	45
hsa0123022	Oral cavity	LP	Biosynthesis of amino acids	36/2418	75/8465	2.68e-04	1.51e-03	9.74e-04	36
hsa0123032	Oral cavity	LP	Biosynthesis of amino acids	36/2418	75/8465	2.68e-04	1.51e-03	9.74e-04	36

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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

ALDH18A1

SNV

Missense_Mutation

c.2063N>C

p.Ile688Thr

p.I688T

P54886

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A1-A0SP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

ALDH18A1

SNV

Missense_Mutation

rs774952464

c.2079N>G

p.Ser693Arg

p.S693R

P54886

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-A2-A04T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ALDH18A1

SNV

Missense_Mutation

c.251G>C

p.Arg84Pro

p.R84P

P54886

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ALDH18A1

SNV

Missense_Mutation

rs375705932

c.2098N>A

p.Val700Ile

p.V700I

P54886

protein_coding

tolerated(0.56)

benign(0.003)

TCGA-AR-A5QP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

ALDH18A1

SNV

Missense_Mutation

c.1108N>A

p.Ala370Thr

p.A370T

P54886

protein_coding

deleterious(0.04)

benign(0.283)

TCGA-C8-A135-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ALDH18A1

SNV

Missense_Mutation

c.800A>T

p.Asp267Val

p.D267V

P54886

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-E2-A152-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

ALDH18A1

SNV

Missense_Mutation

c.376C>T

p.Arg126Cys

p.R126C

P54886

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-GM-A2DI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

ALDH18A1

insertion

Frame_Shift_Ins

novel

c.2288_2289insCATGCCTGTAATCCCAGCACTTTGGGAGGCCAAGG

p.Leu764MetfsTer29

p.L764Mfs*29

P54886

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ALDH18A1

insertion

Frame_Shift_Ins

novel

c.2278_2279insAACTTGTCTTATCTCAGGAGAGAGCCCG

p.Thr760LysfsTer11

p.T760Kfs*11

P54886

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

ALDH18A1

SNV

Missense_Mutation

c.1783N>C

p.Asp595His

p.D595H

P54886

protein_coding

deleterious(0)

benign(0.035)

TCGA-Q1-A73O-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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