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: CD59

Gene summary for CD59

Gene summary.

Gene information	Species	Human
	Gene symbol	CD59
	Gene ID	966
	Gene name	CD59 molecule (CD59 blood group)
	Gene Alias	16.3A5
	Cytomap	11p13
	Gene Type	protein-coding
	GO ID	GO:0001905
	UniProtAcc	P13987

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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
966	CD59	GSM4909282	Human	Breast	IDC	8.31e-18	-5.53e-01	-0.0288
966	CD59	GSM4909285	Human	Breast	IDC	6.10e-31	-6.20e-01	0.21
966	CD59	GSM4909286	Human	Breast	IDC	3.21e-15	-2.54e-01	0.1081
966	CD59	GSM4909290	Human	Breast	IDC	2.10e-33	-9.31e-01	0.2096
966	CD59	GSM4909291	Human	Breast	IDC	2.86e-21	-7.66e-01	0.1753
966	CD59	GSM4909293	Human	Breast	IDC	3.51e-44	-9.30e-01	0.1581
966	CD59	GSM4909294	Human	Breast	IDC	1.29e-48	-9.54e-01	0.2022
966	CD59	GSM4909296	Human	Breast	IDC	5.38e-54	-1.03e+00	0.1524
966	CD59	GSM4909297	Human	Breast	IDC	2.54e-37	-7.38e-01	0.1517
966	CD59	GSM4909298	Human	Breast	IDC	1.04e-20	-4.64e-01	0.1551
966	CD59	GSM4909301	Human	Breast	IDC	9.50e-48	-9.74e-01	0.1577
966	CD59	GSM4909302	Human	Breast	IDC	5.17e-04	-3.44e-01	0.1545
966	CD59	GSM4909304	Human	Breast	IDC	1.86e-20	-4.51e-01	0.1636
966	CD59	GSM4909306	Human	Breast	IDC	6.76e-14	-3.88e-01	0.1564
966	CD59	GSM4909308	Human	Breast	IDC	1.72e-13	-1.99e-01	0.158
966	CD59	GSM4909311	Human	Breast	IDC	4.00e-56	-8.71e-01	0.1534
966	CD59	GSM4909312	Human	Breast	IDC	1.19e-33	-7.38e-01	0.1552
966	CD59	GSM4909313	Human	Breast	IDC	2.56e-03	-1.98e-01	0.0391
966	CD59	GSM4909315	Human	Breast	IDC	8.11e-36	-8.50e-01	0.21
966	CD59	GSM4909316	Human	Breast	IDC	9.94e-12	-8.21e-01	0.21

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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
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
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:00420609	Breast	Precancer	wound healing	48/1080	422/18723	5.48e-06	1.63e-04	48
GO:00508789	Breast	Precancer	regulation of body fluid levels	40/1080	379/18723	1.68e-04	2.77e-03	40
GO:00026836	Breast	Precancer	negative regulation of immune system process	41/1080	434/18723	1.33e-03	1.40e-02	41
GO:00075995	Breast	Precancer	hemostasis	24/1080	222/18723	2.31e-03	2.15e-02	24
GO:00075965	Breast	Precancer	blood coagulation	23/1080	217/18723	3.61e-03	2.98e-02	23
GO:00508175	Breast	Precancer	coagulation	23/1080	222/18723	4.78e-03	3.64e-02	23
GO:004206014	Breast	IDC	wound healing	55/1434	422/18723	7.27e-05	1.45e-03	55
GO:005087813	Breast	IDC	regulation of body fluid levels	50/1434	379/18723	1.12e-04	2.10e-03	50
GO:000268311	Breast	IDC	negative regulation of immune system process	55/1434	434/18723	1.53e-04	2.67e-03	55
GO:00069596	Breast	IDC	humoral immune response	40/1434	317/18723	1.25e-03	1.33e-02	40
GO:00022532	Breast	IDC	activation of immune response	43/1434	375/18723	5.16e-03	3.84e-02	43
GO:000268321	Breast	DCIS	negative regulation of immune system process	57/1390	434/18723	1.81e-05	4.35e-04	57
GO:005087823	Breast	DCIS	regulation of body fluid levels	50/1390	379/18723	5.17e-05	1.06e-03	50
GO:004206024	Breast	DCIS	wound healing	54/1390	422/18723	6.09e-05	1.22e-03	54
GO:000225311	Breast	DCIS	activation of immune response	43/1390	375/18723	2.96e-03	2.54e-02	43
GO:000695911	Breast	DCIS	humoral immune response	37/1390	317/18723	4.16e-03	3.29e-02	37
GO:004206010	Cervix	CC	wound healing	109/2311	422/18723	1.84e-14	1.57e-11	109
GO:00026837	Cervix	CC	negative regulation of immune system process	94/2311	434/18723	2.63e-08	1.87e-06	94
GO:005087810	Cervix	CC	regulation of body fluid levels	78/2311	379/18723	3.20e-06	8.77e-05	78
GO:00022533	Cervix	CC	activation of immune response	72/2311	375/18723	8.26e-05	1.11e-03	72

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04640	Cervix	HSIL_HPV	Hematopoietic cell lineage	18/459	99/8465	4.97e-06	8.10e-05	6.54e-05	18
hsa046401	Cervix	HSIL_HPV	Hematopoietic cell lineage	18/459	99/8465	4.97e-06	8.10e-05	6.54e-05	18
hsa046402	Cervix	N_HPV	Hematopoietic cell lineage	13/349	99/8465	1.98e-04	1.74e-03	1.36e-03	13
hsa046403	Cervix	N_HPV	Hematopoietic cell lineage	13/349	99/8465	1.98e-04	1.74e-03	1.36e-03	13
hsa04610	Liver	NAFLD	Complement and coagulation cascades	35/1043	86/8465	2.48e-11	2.04e-09	1.64e-09	35
hsa046101	Liver	NAFLD	Complement and coagulation cascades	35/1043	86/8465	2.48e-11	2.04e-09	1.64e-09	35
hsa046102	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa046103	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa046104	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57
hsa046105	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
CD59	ICAF	Colorectum	ADJ	TAGLN2,VIM,CRIP2, etc.	2.53e-01
CD59	ICAF	Colorectum	CRC	TAGLN2,VIM,CRIP2, etc.	4.71e-02
CD59	STM	Stomach	ADJ	CD63,TM4SF1,IFI27, etc.	2.81e-01
CD59	STM	Stomach	CAG with IM	CD63,TM4SF1,IFI27, etc.	2.70e-01
CD59	STM	Stomach	CSG	CD63,TM4SF1,IFI27, etc.	2.76e-01
CD59	PTC	Thyroid	ATC	CYBA,B2M,APLP2, etc.	3.94e-01

∗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

CD59

SNV

Missense_Mutation

rs754311428

c.292N>A

p.Glu98Lys

p.E98K

P13987

protein_coding

tolerated(0.56)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CD59

SNV

Missense_Mutation

novel

c.327G>T

p.Glu109Asp

p.E109D

P13987

protein_coding

tolerated(0.17)

benign(0.031)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

CD59

SNV

Missense_Mutation

c.122C>T

p.Ala41Val

p.A41V

P13987

protein_coding

tolerated(0.73)

benign(0.001)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CD59

SNV

Missense_Mutation

novel

c.184N>G

p.Asn62Asp

p.N62D

P13987

protein_coding

tolerated(0.26)

benign(0.15)

TCGA-BG-A221-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CD59

SNV

Missense_Mutation

rs754311428

c.292N>A

p.Glu98Lys

p.E98K

P13987

protein_coding

tolerated(0.56)

benign(0)

TCGA-D1-A160-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CD59

SNV

Missense_Mutation

novel

c.187N>G

p.Lys63Glu

p.K63E

P13987

protein_coding

deleterious(0.02)

benign(0.001)

TCGA-EY-A215-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CD59

SNV

Missense_Mutation

rs146915059

c.65N>T

p.Ser22Leu

p.S22L

P13987

protein_coding

tolerated(0.23)

benign(0.015)

TCGA-FI-A2EW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatinum

CD59

SNV

Missense_Mutation

rs759088791

c.149C>T

p.Ala50Val

p.A50V

P13987

protein_coding

tolerated(0.13)

benign(0.047)

TCGA-SJ-A6ZI-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CD59

insertion

Frame_Shift_Ins

novel

c.229_230insGTTTGAGCATTGCAATTTCAACGACGTCACAA

p.Thr77SerfsTer14

p.T77Sfs*14

P13987

protein_coding

TCGA-44-4112-01

Lung

lung adenocarcinoma

Female

<65

I/II

Chemotherapy

cisplatin

CD59

SNV

Missense_Mutation

novel

c.148N>A

p.Ala50Thr

p.A50T

P13987

protein_coding

tolerated(0.25)

benign(0.044)

TCGA-CQ-7071-01

Oral cavity

head & neck squamous cell carcinoma

Female

>=65

III/IV

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
966	CD59	DRUGGABLE GENOME, CELL SURFACE, KINASE		MBL		17113913

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