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: ALDH9A1

Gene summary for ALDH9A1

Gene summary.

Gene information	Species	Human
	Gene symbol	ALDH9A1
	Gene ID	223
	Gene name	aldehyde dehydrogenase 9 family member A1
	Gene Alias	ALDH4
	Cytomap	1q24.1
	Gene Type	protein-coding
	GO ID	GO:0001505
	UniProtAcc	B9EKV4

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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
223	ALDH9A1	HTA11_78_2000001011	Human	Colorectum	AD	7.93e-04	2.35e-01	-0.1088
223	ALDH9A1	HTA11_347_2000001011	Human	Colorectum	AD	1.42e-10	3.70e-01	-0.1954
223	ALDH9A1	HTA11_5212_2000001011	Human	Colorectum	AD	8.14e-04	3.95e-01	-0.2061
223	ALDH9A1	HTA11_866_3004761011	Human	Colorectum	AD	1.33e-03	2.26e-01	0.096
223	ALDH9A1	HTA11_6801_2000001011	Human	Colorectum	SER	3.45e-02	3.86e-01	0.0171
223	ALDH9A1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.48e-07	3.67e-01	0.294
223	ALDH9A1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	2.06e-02	7.24e-01	0.3487
223	ALDH9A1	HTA11_99999965104_69814	Human	Colorectum	MSS	4.55e-02	1.52e-01	0.281
223	ALDH9A1	HTA11_99999971662_82457	Human	Colorectum	MSS	2.25e-02	2.37e-01	0.3859
223	ALDH9A1	LZE2T	Human	Esophagus	ESCC	5.96e-05	4.49e-01	0.082
223	ALDH9A1	LZE4T	Human	Esophagus	ESCC	7.67e-08	4.01e-01	0.0811
223	ALDH9A1	LZE7T	Human	Esophagus	ESCC	1.25e-03	5.63e-01	0.0667
223	ALDH9A1	LZE8T	Human	Esophagus	ESCC	6.07e-11	9.56e-02	0.067
223	ALDH9A1	LZE20T	Human	Esophagus	ESCC	1.05e-03	-8.89e-02	0.0662
223	ALDH9A1	LZE24T	Human	Esophagus	ESCC	8.55e-06	1.33e-01	0.0596
223	ALDH9A1	LZE21T	Human	Esophagus	ESCC	1.98e-07	7.91e-02	0.0655
223	ALDH9A1	LZE6T	Human	Esophagus	ESCC	1.42e-04	1.49e-01	0.0845
223	ALDH9A1	P2T-E	Human	Esophagus	ESCC	3.59e-54	1.37e+00	0.1177
223	ALDH9A1	P4T-E	Human	Esophagus	ESCC	2.72e-26	1.13e+00	0.1323
223	ALDH9A1	P5T-E	Human	Esophagus	ESCC	7.73e-13	6.90e-02	0.1327

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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
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:0006575	Colorectum	AD	cellular modified amino acid metabolic process	59/3918	188/18723	4.80e-04	5.27e-03	59
GO:0006081	Colorectum	AD	cellular aldehyde metabolic process	22/3918	60/18723	3.64e-03	2.60e-02	22
GO:0042398	Colorectum	AD	cellular modified amino acid biosynthetic process	18/3918	46/18723	3.67e-03	2.60e-02	18
GO:00423981	Colorectum	MSS	cellular modified amino acid biosynthetic process	20/3467	46/18723	8.26e-05	1.35e-03	20
GO:00065751	Colorectum	MSS	cellular modified amino acid metabolic process	55/3467	188/18723	2.16e-04	3.01e-03	55
GO:00060811	Colorectum	MSS	cellular aldehyde metabolic process	21/3467	60/18723	1.81e-03	1.60e-02	21
GO:00060812	Colorectum	MSI-H	cellular aldehyde metabolic process	13/1319	60/18723	2.27e-04	5.94e-03	13
GO:00423982	Colorectum	MSI-H	cellular modified amino acid biosynthetic process	10/1319	46/18723	1.14e-03	1.90e-02	10
GO:00065752	Colorectum	MSI-H	cellular modified amino acid metabolic process	25/1319	188/18723	1.61e-03	2.39e-02	25
GO:00065757	Esophagus	ESCC	cellular modified amino acid metabolic process	112/8552	188/18723	8.31e-05	6.06e-04	112
GO:00423986	Esophagus	ESCC	cellular modified amino acid biosynthetic process	34/8552	46/18723	9.39e-05	6.70e-04	34
GO:00060818	Esophagus	ESCC	cellular aldehyde metabolic process	40/8552	60/18723	8.30e-04	4.28e-03	40
GO:00512623	Esophagus	ESCC	protein tetramerization	54/8552	87/18723	1.50e-03	7.06e-03	54
GO:00512592	Esophagus	ESCC	protein complex oligomerization	130/8552	238/18723	3.29e-03	1.36e-02	130
GO:004239811	Liver	Cirrhotic	cellular modified amino acid biosynthetic process	25/4634	46/18723	1.61e-05	2.19e-04	25
GO:000657511	Liver	Cirrhotic	cellular modified amino acid metabolic process	70/4634	188/18723	9.04e-05	9.69e-04	70
GO:00060815	Liver	Cirrhotic	cellular aldehyde metabolic process	28/4634	60/18723	1.83e-04	1.71e-03	28
GO:004244511	Liver	Cirrhotic	hormone metabolic process	73/4634	218/18723	2.22e-03	1.36e-02	73
GO:000657521	Liver	HCC	cellular modified amino acid metabolic process	119/7958	188/18723	6.47e-09	1.67e-07	119
GO:004239821	Liver	HCC	cellular modified amino acid biosynthetic process	34/7958	46/18723	1.53e-05	1.67e-04	34

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00620	Colorectum	AD	Pyruvate metabolism	28/2092	47/8465	3.71e-07	5.41e-06	3.45e-06	28
hsa00010	Colorectum	AD	Glycolysis / Gluconeogenesis	34/2092	67/8465	3.63e-06	4.34e-05	2.77e-05	34
hsa00280	Colorectum	AD	Valine, leucine and isoleucine degradation	25/2092	48/8465	3.97e-05	3.41e-04	2.18e-04	25
hsa00330	Colorectum	AD	Arginine and proline metabolism	23/2092	50/8465	8.27e-04	5.90e-03	3.76e-03	23
hsa00310	Colorectum	AD	Lysine degradation	27/2092	63/8465	1.17e-03	7.75e-03	4.94e-03	27
hsa00071	Colorectum	AD	Fatty acid degradation	20/2092	43/8465	1.50e-03	8.69e-03	5.54e-03	20
hsa00561	Colorectum	AD	Glycerolipid metabolism	24/2092	63/8465	1.25e-02	4.54e-02	2.90e-02	24
hsa006201	Colorectum	AD	Pyruvate metabolism	28/2092	47/8465	3.71e-07	5.41e-06	3.45e-06	28
hsa000101	Colorectum	AD	Glycolysis / Gluconeogenesis	34/2092	67/8465	3.63e-06	4.34e-05	2.77e-05	34
hsa002801	Colorectum	AD	Valine, leucine and isoleucine degradation	25/2092	48/8465	3.97e-05	3.41e-04	2.18e-04	25
hsa003301	Colorectum	AD	Arginine and proline metabolism	23/2092	50/8465	8.27e-04	5.90e-03	3.76e-03	23
hsa003101	Colorectum	AD	Lysine degradation	27/2092	63/8465	1.17e-03	7.75e-03	4.94e-03	27
hsa000711	Colorectum	AD	Fatty acid degradation	20/2092	43/8465	1.50e-03	8.69e-03	5.54e-03	20
hsa005611	Colorectum	AD	Glycerolipid metabolism	24/2092	63/8465	1.25e-02	4.54e-02	2.90e-02	24
hsa006202	Colorectum	SER	Pyruvate metabolism	22/1580	47/8465	9.62e-06	1.33e-04	9.67e-05	22
hsa003302	Colorectum	SER	Arginine and proline metabolism	17/1580	50/8465	7.12e-03	3.77e-02	2.74e-02	17
hsa006203	Colorectum	SER	Pyruvate metabolism	22/1580	47/8465	9.62e-06	1.33e-04	9.67e-05	22
hsa003303	Colorectum	SER	Arginine and proline metabolism	17/1580	50/8465	7.12e-03	3.77e-02	2.74e-02	17
hsa006204	Colorectum	MSS	Pyruvate metabolism	24/1875	47/8465	1.25e-05	1.35e-04	8.27e-05	24
hsa003304	Colorectum	MSS	Arginine and proline metabolism	23/1875	50/8465	1.52e-04	1.24e-03	7.61e-04	23

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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

ALDH9A1

SNV

Missense_Mutation

rs142168163

c.1361G>A

p.Arg454Gln

p.R454Q

P49189

protein_coding

deleterious(0.01)

probably_damaging(0.921)

TCGA-3C-AALK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

ALDH9A1

SNV

Missense_Mutation

c.347N>T

p.Ala116Val

p.A116V

P49189

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

ALDH9A1

SNV

Missense_Mutation

c.500G>C

p.Arg167Thr

p.R167T

P49189

protein_coding

deleterious(0.01)

probably_damaging(0.983)

TCGA-C8-A12K-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ALDH9A1

insertion

Nonsense_Mutation

novel

c.368_369insGGCATGCGCTACCACACCCGGTTAATTTTTTTGTAT

p.Asn123delinsLysAlaCysAlaThrThrProGlyTerPhePheCysIle

p.N123delinsKACATTPG*FFCI

P49189

protein_coding

TCGA-A2-A0CU-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

ALDH9A1

deletion

Frame_Shift_Del

novel

c.219_220delNN

p.Glu74SerfsTer13

p.E74Sfs*13

P49189

protein_coding

TCGA-S3-AA11-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

letrozole

ALDH9A1

SNV

Missense_Mutation

novel

c.710C>A

p.Ala237Asp

p.A237D

P49189

protein_coding

deleterious(0.03)

possibly_damaging(0.514)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ALDH9A1

SNV

Missense_Mutation

rs760770069

c.485N>T

p.Ser162Leu

p.S162L

P49189

protein_coding

deleterious(0.01)

probably_damaging(0.985)

TCGA-Q1-A5R2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ALDH9A1

SNV

Missense_Mutation

c.157G>C

p.Glu53Gln

p.E53Q

P49189

protein_coding

tolerated(0.65)

benign(0.268)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ALDH9A1

SNV

Missense_Mutation

rs755173841

c.967N>C

p.Glu323Gln

p.E323Q

P49189

protein_coding

tolerated(0.1)

benign(0.157)

TCGA-ZJ-AAXU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ALDH9A1

SNV

Missense_Mutation

c.1245N>T

p.Glu415Asp

p.E415D

P49189

protein_coding

deleterious(0)

possibly_damaging(0.829)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

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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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