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:007252125	Esophagus	HGIN	purine-containing compound metabolic process	78/2587	416/18723	2.78e-03	2.73e-02	78
GO:000925920	Esophagus	HGIN	ribonucleotide metabolic process	71/2587	385/18723	6.25e-03	4.97e-02	71
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0046034111	Esophagus	ESCC	ATP metabolic process	189/8552	277/18723	1.99e-14	1.04e-12	189
GO:0006753110	Esophagus	ESCC	nucleoside phosphate metabolic process	288/8552	497/18723	1.80e-08	3.50e-07	288
GO:000701527	Esophagus	ESCC	actin filament organization	259/8552	442/18723	2.37e-08	4.50e-07	259
GO:0019693111	Esophagus	ESCC	ribose phosphate metabolic process	234/8552	396/18723	4.24e-08	7.76e-07	234
GO:0009117111	Esophagus	ESCC	nucleotide metabolic process	282/8552	489/18723	4.70e-08	8.50e-07	282
GO:00059969	Esophagus	ESCC	monosaccharide metabolic process	159/8552	257/18723	1.11e-07	1.81e-06	159
GO:0009141111	Esophagus	ESCC	nucleoside triphosphate metabolic process	78/8552	112/18723	2.36e-07	3.59e-06	78
GO:00193189	Esophagus	ESCC	hexose metabolic process	147/8552	237/18723	2.63e-07	3.94e-06	147
GO:0009259111	Esophagus	ESCC	ribonucleotide metabolic process	224/8552	385/18723	4.41e-07	6.00e-06	224
GO:0072521111	Esophagus	ESCC	purine-containing compound metabolic process	238/8552	416/18723	1.20e-06	1.49e-05	238
GO:0009150111	Esophagus	ESCC	purine ribonucleotide metabolic process	213/8552	368/18723	1.40e-06	1.69e-05	213
GO:0046390110	Esophagus	ESCC	ribose phosphate biosynthetic process	119/8552	190/18723	1.73e-06	2.06e-05	119
GO:0006163111	Esophagus	ESCC	purine nucleotide metabolic process	226/8552	396/18723	2.81e-06	3.21e-05	226
GO:002260420	Esophagus	ESCC	regulation of cell morphogenesis	180/8552	309/18723	5.19e-06	5.45e-05	180
GO:0009144110	Esophagus	ESCC	purine nucleoside triphosphate metabolic process	61/8552	88/18723	6.06e-06	6.23e-05	61
GO:000919918	Esophagus	ESCC	ribonucleoside triphosphate metabolic process	61/8552	89/18723	1.07e-05	1.01e-04	61
GO:000916516	Esophagus	ESCC	nucleotide biosynthetic process	150/8552	254/18723	1.12e-05	1.06e-04	150

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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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