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: ATP8B1

Gene summary for ATP8B1

Gene summary.

Gene information	Species	Human
	Gene symbol	ATP8B1
	Gene ID	5205
	Gene name	ATPase phospholipid transporting 8B1
	Gene Alias	ATPIC
	Cytomap	18q21.31
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	O43520

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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
5205	ATP8B1	CA_HPV_2	Human	Cervix	CC	2.86e-02	1.89e-01	0.0391
5205	ATP8B1	CCI_1	Human	Cervix	CC	7.83e-10	9.43e-01	0.528
5205	ATP8B1	CCI_2	Human	Cervix	CC	1.03e-08	9.17e-01	0.5249
5205	ATP8B1	CCI_3	Human	Cervix	CC	1.29e-11	9.85e-01	0.516
5205	ATP8B1	sample3	Human	Cervix	CC	1.11e-05	1.74e-01	0.1387
5205	ATP8B1	H2	Human	Cervix	HSIL_HPV	1.30e-06	2.46e-01	0.0632
5205	ATP8B1	HTA11_3410_2000001011	Human	Colorectum	AD	1.00e-50	-8.64e-01	0.0155
5205	ATP8B1	HTA11_2951_2000001011	Human	Colorectum	AD	4.43e-11	-9.18e-01	0.0216
5205	ATP8B1	HTA11_347_2000001011	Human	Colorectum	AD	4.33e-20	8.51e-01	-0.1954
5205	ATP8B1	HTA11_3361_2000001011	Human	Colorectum	AD	5.48e-10	-5.58e-01	-0.1207
5205	ATP8B1	HTA11_5216_2000001011	Human	Colorectum	SER	1.17e-04	-4.10e-01	-0.1462
5205	ATP8B1	HTA11_9341_2000001011	Human	Colorectum	SER	2.02e-09	-9.56e-01	-0.00410000000000005
5205	ATP8B1	HTA11_866_3004761011	Human	Colorectum	AD	7.08e-12	-5.49e-01	0.096
5205	ATP8B1	HTA11_9408_2000001011	Human	Colorectum	AD	2.45e-05	-6.36e-01	0.0451
5205	ATP8B1	HTA11_8622_2000001021	Human	Colorectum	SER	1.31e-03	-4.20e-01	0.0528
5205	ATP8B1	HTA11_10711_2000001011	Human	Colorectum	AD	3.45e-11	-6.21e-01	0.0338
5205	ATP8B1	HTA11_7696_3000711011	Human	Colorectum	AD	1.05e-13	-4.75e-01	0.0674
5205	ATP8B1	HTA11_11156_2000001011	Human	Colorectum	AD	4.24e-09	-8.92e-01	0.0397
5205	ATP8B1	HTA11_6818_2000001021	Human	Colorectum	AD	1.06e-12	-6.79e-01	0.0588
5205	ATP8B1	HTA11_99999970781_79442	Human	Colorectum	MSS	3.47e-06	-3.75e-01	0.294

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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
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

∗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:01200328	Cervix	CC	regulation of plasma membrane bounded cell projection assembly	38/2311	186/18723	1.14e-03	9.35e-03	38
GO:00604917	Cervix	CC	regulation of cell projection assembly	38/2311	188/18723	1.40e-03	1.10e-02	38
GO:00300337	Cervix	CC	microvillus assembly	7/2311	16/18723	1.79e-03	1.34e-02	7
GO:00070304	Cervix	CC	Golgi organization	32/2311	157/18723	2.78e-03	1.87e-02	32
GO:00070092	Cervix	CC	plasma membrane organization	28/2311	142/18723	7.85e-03	4.14e-02	28
GO:003003313	Cervix	HSIL_HPV	microvillus assembly	5/737	16/18723	2.83e-04	4.69e-03	5
GO:00325308	Cervix	HSIL_HPV	regulation of microvillus organization	4/737	13/18723	1.28e-03	1.48e-02	4
GO:00325287	Cervix	HSIL_HPV	microvillus organization	5/737	24/18723	2.12e-03	2.17e-02	5
GO:0032530	Colorectum	AD	regulation of microvillus organization	10/3918	13/18723	2.43e-05	4.69e-04	10
GO:0032528	Colorectum	AD	microvillus organization	14/3918	24/18723	6.90e-05	1.11e-03	14
GO:0010876	Colorectum	AD	lipid localization	120/3918	448/18723	1.59e-03	1.33e-02	120
GO:0006869	Colorectum	AD	lipid transport	108/3918	398/18723	1.67e-03	1.39e-02	108
GO:0030033	Colorectum	AD	microvillus assembly	9/3918	16/18723	2.06e-03	1.64e-02	9
GO:0042490	Colorectum	AD	mechanoreceptor differentiation	24/3918	67/18723	3.48e-03	2.52e-02	24
GO:0015698	Colorectum	AD	inorganic anion transport	52/3918	180/18723	6.83e-03	4.22e-02	52
GO:0015748	Colorectum	AD	organophosphate ester transport	42/3918	140/18723	7.04e-03	4.31e-02	42
GO:0060119	Colorectum	AD	inner ear receptor cell development	17/3918	45/18723	7.10e-03	4.33e-02	17
GO:0008202	Colorectum	AD	steroid metabolic process	85/3918	319/18723	8.07e-03	4.75e-02	85
GO:0120032	Colorectum	AD	regulation of plasma membrane bounded cell projection assembly	53/3918	186/18723	8.51e-03	4.97e-02	53
GO:00325301	Colorectum	SER	regulation of microvillus organization	10/2897	13/18723	1.41e-06	6.46e-05	10

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

ATP8B1

SNV

Missense_Mutation

novel

c.794N>T

p.Cys265Phe

p.C265F

O43520

protein_coding

deleterious(0)

possibly_damaging(0.822)

TCGA-A2-A25D-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

ATP8B1

SNV

Missense_Mutation

c.2584N>T

p.Ala862Ser

p.A862S

O43520

protein_coding

tolerated(0.12)

benign(0.178)

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ATP8B1

SNV

Missense_Mutation

novel

c.88N>A

p.Glu30Lys

p.E30K

O43520

protein_coding

tolerated_low_confidence(0.17)

benign(0.339)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ATP8B1

SNV

Missense_Mutation

novel

c.2224A>G

p.Ile742Val

p.I742V

O43520

protein_coding

tolerated(0.06)

benign(0.298)

TCGA-BH-A1FU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ATP8B1

SNV

Missense_Mutation

novel

c.1663G>A

p.Glu555Lys

p.E555K

O43520

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

ATP8B1

insertion

Frame_Shift_Ins

novel

c.225_226insTTCTCCTGCCTCAGCCTCC

p.Gln76PhefsTer19

p.Q76Ffs*19

O43520

protein_coding

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ATP8B1

insertion

Nonsense_Mutation

novel

c.3405_3406insATCTGAATACAATCAATTTCCATTAGAAAGAAGGAGAGAGTAGAGG

p.Ala1136IlefsTer2

p.A1136Ifs*2

O43520

protein_coding

TCGA-BH-A0HO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

ATP8B1

SNV

Missense_Mutation

novel

c.3418N>A

p.Leu1140Met

p.L1140M

O43520

protein_coding

tolerated(0.21)

probably_damaging(0.998)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ATP8B1

SNV

Missense_Mutation

novel

c.3190N>C

p.Glu1064Gln

p.E1064Q

O43520

protein_coding

tolerated(0.25)

probably_damaging(0.969)

TCGA-VS-A9UY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ATP8B1

SNV

Missense_Mutation

c.46N>G

p.Gln16Glu

p.Q16E

O43520

protein_coding

tolerated_low_confidence(0.16)

benign(0.001)

TCGA-VS-A9UY-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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