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: C5

Gene summary for C5

Gene summary.

Gene information	Species	Human
	Gene symbol	C5
	Gene ID	727
	Gene name	complement C5
	Gene Alias	C5D
	Cytomap	9q33.2
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	P01031

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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
727	C5	NAFLD1	Human	Liver	NAFLD	8.50e-14	1.34e+00	-0.04
727	C5	HCC1_Meng	Human	Liver	HCC	7.54e-118	1.55e-02	0.0246
727	C5	HCC2_Meng	Human	Liver	HCC	1.46e-12	-4.63e-01	0.0107
727	C5	cirrhotic1	Human	Liver	Cirrhotic	5.11e-14	-2.67e-01	0.0202
727	C5	cirrhotic2	Human	Liver	Cirrhotic	3.10e-19	-1.43e-01	0.0201
727	C5	cirrhotic3	Human	Liver	Cirrhotic	6.66e-08	-3.19e-01	0.0215
727	C5	HCC2	Human	Liver	HCC	1.49e-09	3.88e+00	0.5341
727	C5	Pt13.a	Human	Liver	HCC	2.70e-10	-3.08e-01	0.021
727	C5	Pt13.b	Human	Liver	HCC	4.55e-15	-2.59e-01	0.0251
727	C5	Pt14.a	Human	Liver	HCC	3.07e-05	-7.42e-02	0.0169
727	C5	Pt14.b	Human	Liver	HCC	2.17e-06	1.23e-02	0.018
727	C5	Pt14.d	Human	Liver	HCC	7.68e-10	-2.55e-01	0.0143
727	C5	S028	Human	Liver	HCC	2.48e-07	4.73e-01	0.2503
727	C5	S029	Human	Liver	HCC	2.29e-10	7.92e-01	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:001056316	Endometrium	AEH	negative regulation of phosphorus metabolic process	77/2100	442/18723	5.54e-05	8.79e-04	77
GO:00108339	Endometrium	AEH	telomere maintenance via telomere lengthening	22/2100	81/18723	5.82e-05	9.12e-04	22
GO:000815410	Endometrium	AEH	actin polymerization or depolymerization	44/2100	218/18723	7.64e-05	1.15e-03	44
GO:005134816	Endometrium	AEH	negative regulation of transferase activity	51/2100	268/18723	1.06e-04	1.52e-03	51
GO:00322069	Endometrium	AEH	positive regulation of telomere maintenance	16/2100	52/18723	1.18e-04	1.66e-03	16
GO:19018009	Endometrium	AEH	positive regulation of proteasomal protein catabolic process	27/2100	114/18723	1.21e-04	1.67e-03	27
GO:003004110	Endometrium	AEH	actin filament polymerization	39/2100	191/18723	1.47e-04	1.96e-03	39
GO:00322105	Endometrium	AEH	regulation of telomere maintenance via telomerase	16/2100	53/18723	1.52e-04	2.00e-03	16
GO:00718977	Endometrium	AEH	DNA biosynthetic process	37/2100	180/18723	1.87e-04	2.39e-03	37
GO:003367414	Endometrium	AEH	positive regulation of kinase activity	78/2100	467/18723	2.03e-04	2.54e-03	78
GO:00068886	Endometrium	AEH	endoplasmic reticulum to Golgi vesicle-mediated transport	29/2100	130/18723	2.11e-04	2.59e-03	29
GO:20005739	Endometrium	AEH	positive regulation of DNA biosynthetic process	18/2100	66/18723	2.52e-04	2.99e-03	18
GO:19908235	Endometrium	AEH	response to leukemia inhibitory factor	23/2100	95/18723	2.65e-04	3.09e-03	23
GO:00457877	Endometrium	AEH	positive regulation of cell cycle	56/2100	313/18723	2.73e-04	3.14e-03	56
GO:00714799	Endometrium	AEH	cellular response to ionizing radiation	19/2100	72/18723	2.74e-04	3.14e-03	19
GO:19043568	Endometrium	AEH	regulation of telomere maintenance via telomere lengthening	17/2100	61/18723	2.80e-04	3.21e-03	17
GO:000193315	Endometrium	AEH	negative regulation of protein phosphorylation	60/2100	342/18723	2.89e-04	3.31e-03	60
GO:00458609	Endometrium	AEH	positive regulation of protein kinase activity	66/2100	386/18723	3.14e-04	3.53e-03	66
GO:003083310	Endometrium	AEH	regulation of actin filament polymerization	35/2100	172/18723	3.36e-04	3.73e-03	35
GO:00488635	Endometrium	AEH	stem cell differentiation	40/2100	206/18723	3.67e-04	3.99e-03	40

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517114	Liver	NAFLD	Coronavirus disease - COVID-19	111/1043	232/8465	1.01e-41	3.32e-39	2.67e-39	111
hsa04610	Liver	NAFLD	Complement and coagulation cascades	35/1043	86/8465	2.48e-11	2.04e-09	1.64e-09	35
hsa0481010	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0517115	Liver	NAFLD	Coronavirus disease - COVID-19	111/1043	232/8465	1.01e-41	3.32e-39	2.67e-39	111
hsa046101	Liver	NAFLD	Complement and coagulation cascades	35/1043	86/8465	2.48e-11	2.04e-09	1.64e-09	35
hsa0481011	Liver	NAFLD	Regulation of actin cytoskeleton	50/1043	229/8465	3.01e-05	7.59e-04	6.11e-04	50
hsa0517122	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa0502014	Liver	Cirrhotic	Prion disease	152/2530	273/8465	1.84e-19	8.78e-18	5.41e-18	152
hsa046102	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa0481021	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa05133	Liver	Cirrhotic	Pertussis	37/2530	76/8465	4.17e-04	2.57e-03	1.58e-03	37
hsa04936	Liver	Cirrhotic	Alcoholic liver disease	60/2530	142/8465	1.07e-03	5.85e-03	3.61e-03	60
hsa0517132	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa0502015	Liver	Cirrhotic	Prion disease	152/2530	273/8465	1.84e-19	8.78e-18	5.41e-18	152
hsa046103	Liver	Cirrhotic	Complement and coagulation cascades	48/2530	86/8465	4.41e-07	5.44e-06	3.35e-06	48
hsa0481031	Liver	Cirrhotic	Regulation of actin cytoskeleton	100/2530	229/8465	5.28e-06	5.50e-05	3.39e-05	100
hsa051331	Liver	Cirrhotic	Pertussis	37/2530	76/8465	4.17e-04	2.57e-03	1.58e-03	37
hsa049361	Liver	Cirrhotic	Alcoholic liver disease	60/2530	142/8465	1.07e-03	5.85e-03	3.61e-03	60
hsa0502022	Liver	HCC	Prion disease	195/4020	273/8465	3.26e-16	1.56e-14	8.67e-15	195
hsa0517142	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167

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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
C5	C5AR1	HC_C5AR1	COMPLEMENT	Cervix	CC
C5	C5AR1	HC_C5AR1	COMPLEMENT	Esophagus	ESCC
C5	C5AR1	HC_C5AR1	COMPLEMENT	Liver	HCC
C5	C5AR1	HC_C5AR1	COMPLEMENT	Liver	Healthy
C5	C5AR1	HC_C5AR1	COMPLEMENT	Liver	Precancer
C5	C5AR1	HC_C5AR1	COMPLEMENT	Lung	AAH

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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

SNV

Missense_Mutation

c.4015G>C

p.Glu1339Gln

p.E1339Q

P01031

protein_coding

tolerated(0.2)

probably_damaging(0.946)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SNV

Missense_Mutation

c.759N>T

p.Arg253Ser

p.R253S

P01031

protein_coding

tolerated(0.5)

benign(0.003)

TCGA-A2-A25E-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

SNV

Missense_Mutation

c.2762N>G

p.Glu921Gly

p.E921G

P01031

protein_coding

deleterious(0)

possibly_damaging(0.655)

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

SNV

Missense_Mutation

rs758293412

c.3422G>A

p.Ser1141Asn

p.S1141N

P01031

protein_coding

deleterious(0.04)

benign(0.003)

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

SNV

Missense_Mutation

c.1086N>A

p.Phe362Leu

p.F362L

P01031

protein_coding

deleterious(0)

possibly_damaging(0.73)

TCGA-A8-A09G-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

SNV

Missense_Mutation

c.1118T>C

p.Val373Ala

p.V373A

P01031

protein_coding

tolerated(0.08)

benign(0.007)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

novel

c.4517N>T

p.Thr1506Ile

p.T1506I

P01031

protein_coding

deleterious(0.03)

probably_damaging(0.992)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

rs369245774

c.2017N>A

p.Leu673Ile

p.L673I

P01031

protein_coding

tolerated(0.08)

benign(0.003)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

novel

c.711N>A

p.Phe237Leu

p.F237L

P01031

protein_coding

deleterious(0.01)

possibly_damaging(0.6)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

novel

c.1643N>A

p.Gly548Glu

p.G548E

P01031

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AN-A0XW-01

Breast

breast invasive 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
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME		eculizumab	ECULIZUMAB	24521109
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME		LFG-316	TESIDOLUMAB	24860651
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME		IFX-1
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL1201828	ECULIZUMAB
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME	inhibitor	CHEMBL2107979	PEXELIZUMAB
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME		SAND-5		22990692
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME		Ravulizumab	RAVULIZUMAB
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME		NNC-0151-0000-0000
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME		ECULIZUMAB	ECULIZUMAB
727	C5	PROTEASE INHIBITOR, DRUGGABLE GENOME, ENZYME		ARC-1905	AVACINCAPTAD PEGOL SODIUM

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