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: ABCA1

Gene summary for ABCA1

Gene summary.

Gene information	Species	Human
	Gene symbol	ABCA1
	Gene ID	19
	Gene name	ATP binding cassette subfamily A member 1
	Gene Alias	ABC-1
	Cytomap	9q31.1
	Gene Type	protein-coding
	GO ID	GO:0002237
	UniProtAcc	B2RUU2

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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
19	ABCA1	CCI_2	Human	Cervix	CC	9.09e-05	9.12e-01	0.5249
19	ABCA1	CCI_3	Human	Cervix	CC	1.24e-08	1.17e+00	0.516
19	ABCA1	LZE7T	Human	Esophagus	ESCC	7.08e-03	3.46e-02	0.0667
19	ABCA1	LZE8T	Human	Esophagus	ESCC	2.57e-05	5.82e-02	0.067
19	ABCA1	LZE20T	Human	Esophagus	ESCC	7.34e-04	1.99e-01	0.0662
19	ABCA1	LZE24T	Human	Esophagus	ESCC	1.98e-05	1.43e-01	0.0596
19	ABCA1	LZE21T	Human	Esophagus	ESCC	2.89e-05	6.96e-01	0.0655
19	ABCA1	P1T-E	Human	Esophagus	ESCC	5.06e-07	5.95e-01	0.0875
19	ABCA1	P2T-E	Human	Esophagus	ESCC	3.51e-20	5.72e-01	0.1177
19	ABCA1	P4T-E	Human	Esophagus	ESCC	1.65e-15	4.22e-01	0.1323
19	ABCA1	P5T-E	Human	Esophagus	ESCC	2.00e-23	6.40e-01	0.1327
19	ABCA1	P8T-E	Human	Esophagus	ESCC	3.59e-12	3.73e-01	0.0889
19	ABCA1	P9T-E	Human	Esophagus	ESCC	7.21e-18	5.04e-01	0.1131
19	ABCA1	P11T-E	Human	Esophagus	ESCC	3.08e-13	7.69e-01	0.1426
19	ABCA1	P12T-E	Human	Esophagus	ESCC	1.22e-17	4.65e-01	0.1122
19	ABCA1	P15T-E	Human	Esophagus	ESCC	4.34e-25	6.77e-01	0.1149
19	ABCA1	P16T-E	Human	Esophagus	ESCC	2.98e-05	-7.98e-02	0.1153
19	ABCA1	P20T-E	Human	Esophagus	ESCC	9.66e-09	2.69e-01	0.1124
19	ABCA1	P21T-E	Human	Esophagus	ESCC	9.65e-11	3.21e-01	0.1617
19	ABCA1	P22T-E	Human	Esophagus	ESCC	1.32e-08	3.33e-01	0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:00510566	Cervix	CC	regulation of small GTPase mediated signal transduction	75/2311	302/18723	1.54e-09	1.74e-07	75
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:00512359	Cervix	CC	maintenance of location	78/2311	327/18723	5.18e-09	4.92e-07	78
GO:00072656	Cervix	CC	Ras protein signal transduction	79/2311	337/18723	9.49e-09	7.77e-07	79
GO:00022379	Cervix	CC	response to molecule of bacterial origin	78/2311	363/18723	5.55e-07	2.06e-05	78
GO:00324969	Cervix	CC	response to lipopolysaccharide	74/2311	343/18723	9.15e-07	3.25e-05	74
GO:003133410	Cervix	CC	positive regulation of protein-containing complex assembly	55/2311	237/18723	2.25e-06	6.73e-05	55
GO:003166710	Cervix	CC	response to nutrient levels	92/2311	474/18723	5.80e-06	1.42e-04	92
GO:00072666	Cervix	CC	Rho protein signal transduction	35/2311	137/18723	1.77e-05	3.33e-04	35
GO:00465785	Cervix	CC	regulation of Ras protein signal transduction	44/2311	189/18723	2.05e-05	3.73e-04	44
GO:00301008	Cervix	CC	regulation of endocytosis	47/2311	211/18723	3.65e-05	5.82e-04	47
GO:00458077	Cervix	CC	positive regulation of endocytosis	27/2311	100/18723	5.55e-05	8.10e-04	27
GO:00161977	Cervix	CC	endosomal transport	48/2311	230/18723	1.65e-04	1.97e-03	48
GO:00350235	Cervix	CC	regulation of Rho protein signal transduction	22/2311	86/18723	5.93e-04	5.60e-03	22
GO:00714042	Cervix	CC	cellular response to low-density lipoprotein particle stimulus	9/2311	22/18723	7.19e-04	6.49e-03	9
GO:00712228	Cervix	CC	cellular response to lipopolysaccharide	41/2311	209/18723	1.69e-03	1.29e-02	41
GO:00094109	Cervix	CC	response to xenobiotic stimulus	78/2311	462/18723	2.39e-03	1.70e-02	78
GO:00712168	Cervix	CC	cellular response to biotic stimulus	46/2311	246/18723	2.53e-03	1.76e-02	46
GO:00160506	Cervix	CC	vesicle organization	54/2311	300/18723	2.71e-03	1.85e-02	54
GO:00712198	Cervix	CC	cellular response to molecule of bacterial origin	42/2311	221/18723	2.79e-03	1.87e-02	42

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa05417110	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa05417310	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa049792	Liver	Cirrhotic	Cholesterol metabolism	30/2530	51/8465	1.59e-05	1.39e-04	8.60e-05	30
hsa0541722	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa049793	Liver	Cirrhotic	Cholesterol metabolism	30/2530	51/8465	1.59e-05	1.39e-04	8.60e-05	30
hsa0541732	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa049794	Liver	HCC	Cholesterol metabolism	41/4020	51/8465	1.33e-06	1.35e-05	7.49e-06	41
hsa020102	Liver	HCC	ABC transporters	29/4020	45/8465	1.62e-02	3.88e-02	2.16e-02	29
hsa0541742	Liver	HCC	Lipid and atherosclerosis	118/4020	215/8465	1.66e-02	3.92e-02	2.18e-02	118
hsa049795	Liver	HCC	Cholesterol metabolism	41/4020	51/8465	1.33e-06	1.35e-05	7.49e-06	41
hsa020103	Liver	HCC	ABC transporters	29/4020	45/8465	1.62e-02	3.88e-02	2.16e-02	29
hsa0541752	Liver	HCC	Lipid and atherosclerosis	118/4020	215/8465	1.66e-02	3.92e-02	2.18e-02	118
hsa0541730	Oral cavity	OSCC	Lipid and atherosclerosis	131/3704	215/8465	2.20e-07	1.45e-06	7.37e-07	131
hsa05417113	Oral cavity	OSCC	Lipid and atherosclerosis	131/3704	215/8465	2.20e-07	1.45e-06	7.37e-07	131

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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

ABCA1

SNV

Missense_Mutation

novel

c.1055N>A

p.Thr352Asn

p.T352N

O95477

protein_coding

tolerated(0.06)

benign(0.014)

TCGA-A2-A0CR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ABCA1

SNV

Missense_Mutation

c.2179N>T

p.Val727Leu

p.V727L

O95477

protein_coding

tolerated(0.11)

benign(0.011)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ABCA1

SNV

Missense_Mutation

c.5552N>A

p.Arg1851Gln

p.R1851Q

O95477

protein_coding

deleterious(0.02)

benign(0.015)

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ABCA1

SNV

Missense_Mutation

novel

c.4559N>T

p.Ser1520Ile

p.S1520I

O95477

protein_coding

deleterious(0.01)

probably_damaging(0.93)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ABCA1

SNV

Missense_Mutation

novel

c.380N>C

p.Lys127Thr

p.K127T

O95477

protein_coding

tolerated(0.22)

benign(0.007)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ABCA1

SNV

Missense_Mutation

c.6082N>T

p.Ala2028Ser

p.A2028S

O95477

protein_coding

tolerated(0.11)

benign(0.038)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ABCA1

SNV

Missense_Mutation

c.5240N>T

p.Trp1747Leu

p.W1747L

O95477

protein_coding

deleterious(0)

possibly_damaging(0.708)

TCGA-AR-A24Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ABCA1

SNV

Missense_Mutation

c.6065G>C

p.Gly2022Ala

p.G2022A

O95477

protein_coding

tolerated(1)

benign(0.006)

TCGA-B6-A0RI-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ABCA1

SNV

Missense_Mutation

c.4457N>T

p.Pro1486Leu

p.P1486L

O95477

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0HN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ABCA1

SNV

Missense_Mutation

novel

c.363N>A

p.Ser121Arg

p.S121R

O95477

protein_coding

tolerated(0.48)

benign(0.005)

TCGA-D8-A27G-01

Breast

breast invasive 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
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		pravastatin	PRAVASTATIN	19673941,20031551
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	CHEMBL608	PROBUCOL
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE	inhibitor	178103851	PROBUCOL
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		fenofibrate	FENOFIBRATE
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		315661263
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		atorvastatin	ATORVASTATIN	20031551
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		CSA	CYCLOSPORINE	15084924
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		simvastatin	SIMVASTATIN	20031551
19	ABCA1	TRANSPORTER, DRUGGABLE GENOME, ABC TRANSPORTER, CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE		Probucol	PROBUCOL

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