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: ALDOA

Gene summary for ALDOA

Gene summary.

Gene information	Species	Human
	Gene symbol	ALDOA
	Gene ID	226
	Gene name	aldolase, fructose-bisphosphate A
	Gene Alias	ALDA
	Cytomap	16p11.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P04075

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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
226	ALDOA	GSM4909277	Human	Breast	Precancer	1.20e-03	-7.89e-01	0.0177
226	ALDOA	GSM4909280	Human	Breast	Precancer	4.55e-03	-6.72e-01	0.0305
226	ALDOA	GSM4909281	Human	Breast	IDC	1.12e-19	-5.82e-01	0.21
226	ALDOA	GSM4909282	Human	Breast	IDC	2.06e-26	-7.05e-01	-0.0288
226	ALDOA	GSM4909285	Human	Breast	IDC	1.09e-28	-6.97e-01	0.21
226	ALDOA	GSM4909286	Human	Breast	IDC	2.62e-28	-7.09e-01	0.1081
226	ALDOA	GSM4909287	Human	Breast	IDC	3.35e-28	-6.95e-01	0.2057
226	ALDOA	GSM4909288	Human	Breast	IDC	3.76e-11	-7.75e-01	0.0988
226	ALDOA	GSM4909290	Human	Breast	IDC	5.73e-17	-6.27e-01	0.2096
226	ALDOA	GSM4909291	Human	Breast	IDC	1.19e-02	-3.28e-01	0.1753
226	ALDOA	GSM4909293	Human	Breast	IDC	2.30e-23	-6.36e-01	0.1581
226	ALDOA	GSM4909294	Human	Breast	IDC	2.25e-29	-7.17e-01	0.2022
226	ALDOA	GSM4909295	Human	Breast	IDC	3.98e-07	-5.06e-01	0.0898
226	ALDOA	GSM4909296	Human	Breast	IDC	6.98e-14	-5.53e-01	0.1524
226	ALDOA	GSM4909297	Human	Breast	IDC	5.99e-23	-6.91e-01	0.1517
226	ALDOA	GSM4909298	Human	Breast	IDC	2.68e-25	-7.04e-01	0.1551
226	ALDOA	GSM4909299	Human	Breast	IDC	1.48e-28	-7.23e-01	0.035
226	ALDOA	GSM4909300	Human	Breast	IDC	2.99e-02	-3.92e-01	0.0334
226	ALDOA	GSM4909301	Human	Breast	IDC	3.65e-22	-6.77e-01	0.1577
226	ALDOA	GSM4909302	Human	Breast	IDC	2.11e-11	-4.81e-01	0.1545

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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
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:001969319	Oral cavity	OSCC	ribose phosphate metabolic process	199/7305	396/18723	2.97e-06	3.64e-05	199
GO:000836016	Oral cavity	OSCC	regulation of cell shape	88/7305	154/18723	3.73e-06	4.42e-05	88
GO:000925919	Oral cavity	OSCC	ribonucleotide metabolic process	189/7305	385/18723	3.18e-05	2.87e-04	189
GO:000913217	Oral cavity	OSCC	nucleoside diphosphate metabolic process	70/7305	124/18723	6.03e-05	4.95e-04	70
GO:0051259	Oral cavity	OSCC	protein complex oligomerization	121/7305	238/18723	1.29e-04	9.21e-04	121
GO:004693917	Oral cavity	OSCC	nucleotide phosphorylation	58/7305	101/18723	1.33e-04	9.44e-04	58
GO:007252120	Oral cavity	OSCC	purine-containing compound metabolic process	199/7305	416/18723	1.34e-04	9.53e-04	199
GO:000915020	Oral cavity	OSCC	purine ribonucleotide metabolic process	178/7305	368/18723	1.45e-04	1.02e-03	178
GO:00059968	Oral cavity	OSCC	monosaccharide metabolic process	129/7305	257/18723	1.63e-04	1.13e-03	129
GO:000918518	Oral cavity	OSCC	ribonucleoside diphosphate metabolic process	60/7305	106/18723	1.78e-04	1.21e-03	60
GO:000913519	Oral cavity	OSCC	purine nucleoside diphosphate metabolic process	58/7305	103/18723	2.73e-04	1.73e-03	58
GO:000917919	Oral cavity	OSCC	purine ribonucleoside diphosphate metabolic process	58/7305	103/18723	2.73e-04	1.73e-03	58
GO:000616517	Oral cavity	OSCC	nucleoside diphosphate phosphorylation	56/7305	99/18723	2.95e-04	1.85e-03	56
GO:000616320	Oral cavity	OSCC	purine nucleotide metabolic process	188/7305	396/18723	3.31e-04	2.04e-03	188
GO:00193188	Oral cavity	OSCC	hexose metabolic process	118/7305	237/18723	4.53e-04	2.73e-03	118
GO:004603117	Oral cavity	OSCC	ADP metabolic process	51/7305	90/18723	5.08e-04	2.97e-03	51
GO:19012938	Oral cavity	OSCC	nucleoside phosphate biosynthetic process	125/7305	256/18723	8.32e-04	4.41e-03	125
GO:00091658	Oral cavity	OSCC	nucleotide biosynthetic process	124/7305	254/18723	8.79e-04	4.63e-03	124
GO:004639017	Oral cavity	OSCC	ribose phosphate biosynthetic process	95/7305	190/18723	1.30e-03	6.46e-03	95
GO:000609017	Oral cavity	OSCC	pyruvate metabolic process	57/7305	106/18723	1.42e-03	6.84e-03	57

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa01200	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa00010	Colorectum	AD	Glycolysis / Gluconeogenesis	34/2092	67/8465	3.63e-06	4.34e-05	2.77e-05	34
hsa01230	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa012001	Colorectum	AD	Carbon metabolism	55/2092	115/8465	5.53e-08	8.42e-07	5.37e-07	55
hsa000101	Colorectum	AD	Glycolysis / Gluconeogenesis	34/2092	67/8465	3.63e-06	4.34e-05	2.77e-05	34
hsa012301	Colorectum	AD	Biosynthesis of amino acids	28/2092	75/8465	9.99e-03	3.89e-02	2.48e-02	28
hsa012002	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40
hsa040662	Colorectum	SER	HIF-1 signaling pathway	36/1580	109/8465	2.27e-04	2.15e-03	1.56e-03	36
hsa000102	Colorectum	SER	Glycolysis / Gluconeogenesis	24/1580	67/8465	6.62e-04	5.36e-03	3.89e-03	24
hsa012302	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
hsa012003	Colorectum	SER	Carbon metabolism	40/1580	115/8465	2.77e-05	3.41e-04	2.47e-04	40
hsa040663	Colorectum	SER	HIF-1 signaling pathway	36/1580	109/8465	2.27e-04	2.15e-03	1.56e-03	36
hsa000103	Colorectum	SER	Glycolysis / Gluconeogenesis	24/1580	67/8465	6.62e-04	5.36e-03	3.89e-03	24
hsa012303	Colorectum	SER	Biosynthesis of amino acids	23/1580	75/8465	8.11e-03	4.14e-02	3.01e-02	23
hsa012004	Colorectum	MSS	Carbon metabolism	43/1875	115/8465	1.37e-04	1.17e-03	7.19e-04	43
hsa000104	Colorectum	MSS	Glycolysis / Gluconeogenesis	28/1875	67/8465	2.36e-04	1.81e-03	1.11e-03	28
hsa040664	Colorectum	MSS	HIF-1 signaling pathway	39/1875	109/8465	7.61e-04	5.00e-03	3.06e-03	39
hsa012005	Colorectum	MSS	Carbon metabolism	43/1875	115/8465	1.37e-04	1.17e-03	7.19e-04	43
hsa000105	Colorectum	MSS	Glycolysis / Gluconeogenesis	28/1875	67/8465	2.36e-04	1.81e-03	1.11e-03	28
hsa040665	Colorectum	MSS	HIF-1 signaling pathway	39/1875	109/8465	7.61e-04	5.00e-03	3.06e-03	39

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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

ALDOA

SNV

Missense_Mutation

c.641C>T

p.Ser214Leu

p.S214L

P04075

protein_coding

deleterious(0)

possibly_damaging(0.833)

TCGA-A8-A06Q-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ALDOA

SNV

Missense_Mutation

c.987G>C

p.Gln329His

p.Q329H

P04075

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ALDOA

SNV

Missense_Mutation

c.490N>C

p.Asp164His

p.D164H

P04075

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-BH-A0BZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

ALDOA

SNV

Missense_Mutation

c.562N>G

p.Arg188Gly

p.R188G

P04075

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-BH-A0HL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ALDOA

SNV

Missense_Mutation

rs201658390

c.929C>T

p.Ala310Val

p.A310V

P04075

protein_coding

tolerated(0.12)

benign(0.091)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ALDOA

SNV

Missense_Mutation

c.817N>A

p.Asp273Asn

p.D273N

P04075

protein_coding

deleterious(0)

benign(0.036)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ALDOA

insertion

Frame_Shift_Ins

novel

c.678_679insT

p.Arg227SerfsTer18

p.R227Sfs*18

P04075

protein_coding

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ALDOA

insertion

Nonsense_Mutation

novel

c.679_680insTCAGAAGCTCAGGGAAGTGAAGT

p.Arg227LeufsTer7

p.R227Lfs*7

P04075

protein_coding

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ALDOA

insertion

Nonsense_Mutation

novel

c.1253_1254insGAGTCCACTGGTGCGGGCAGGAGACAGAATGGG

p.Tyr418delinsTer

p.Y418delins*

P04075

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

ALDOA

SNV

Missense_Mutation

rs756789043

c.1249G>A

p.Ala417Thr

p.A417T

P04075

protein_coding

tolerated(0.18)

possibly_damaging(0.868)

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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