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: C9

Gene summary for C9

Gene summary.

Gene information	Species	Human
	Gene symbol	C9
	Gene ID	735
	Gene name	complement C9
	Gene Alias	ARMD15
	Cytomap	5p13.1
	Gene Type	protein-coding
	GO ID	GO:0001906
	UniProtAcc	P02748

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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
735	C9	HTA11_2487_2000001011	Human	Colorectum	SER	9.54e-07	2.54e-01	-0.1808
735	C9	HTA11_1938_2000001011	Human	Colorectum	AD	3.78e-11	4.19e-01	-0.0811
735	C9	HTA11_347_2000001011	Human	Colorectum	AD	1.84e-04	1.79e-01	-0.1954
735	C9	HTA11_2112_2000001011	Human	Colorectum	SER	6.32e-08	4.67e-01	-0.2196
735	C9	HTA11_3361_2000001011	Human	Colorectum	AD	3.81e-04	2.55e-01	-0.1207
735	C9	HTA11_83_2000001011	Human	Colorectum	SER	1.88e-09	3.58e-01	-0.1526
735	C9	HTA11_696_2000001011	Human	Colorectum	AD	3.67e-25	4.64e-01	-0.1464
735	C9	HTA11_866_2000001011	Human	Colorectum	AD	1.58e-09	2.35e-01	-0.1001
735	C9	HTA11_1391_2000001011	Human	Colorectum	AD	8.58e-12	3.53e-01	-0.059
735	C9	HTA11_5216_2000001011	Human	Colorectum	SER	2.74e-05	3.76e-01	-0.1462
735	C9	HTA11_546_2000001011	Human	Colorectum	AD	3.93e-02	2.02e-01	-0.0842
735	C9	HTA11_7663_2000001011	Human	Colorectum	SER	3.70e-02	2.97e-01	0.0131
735	C9	HTA11_7696_3000711011	Human	Colorectum	AD	9.91e-03	1.09e-01	0.0674
735	C9	HTA11_6818_2000001011	Human	Colorectum	AD	4.15e-06	4.13e-01	0.0112
735	C9	HTA11_6818_2000001021	Human	Colorectum	AD	2.40e-10	4.06e-01	0.0588
735	C9	HTA11_99999970781_79442	Human	Colorectum	MSS	1.67e-02	1.12e-01	0.294
735	C9	HTA11_99999971662_82457	Human	Colorectum	MSS	1.78e-05	1.89e-01	0.3859
735	C9	HTA11_99999974143_84620	Human	Colorectum	MSS	3.09e-04	1.73e-01	0.3005

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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

∗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:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:19026008	Breast	Precancer	proton transmembrane transport	39/1080	157/18723	4.18e-15	1.18e-12	39
GO:20012445	Breast	Precancer	positive regulation of intrinsic apoptotic signaling pathway	17/1080	58/18723	1.59e-08	1.12e-06	17
GO:20012356	Breast	Precancer	positive regulation of apoptotic signaling pathway	24/1080	126/18723	1.98e-07	1.01e-05	24
GO:00487329	Breast	Precancer	gland development	49/1080	436/18723	6.11e-06	1.73e-04	49
GO:00702933	Breast	Precancer	renal absorption	6/1080	17/18723	2.59e-04	3.83e-03	6
GO:00085445	Breast	Precancer	epidermis development	35/1080	324/18723	2.71e-04	3.96e-03	35
GO:00099136	Breast	Precancer	epidermal cell differentiation	23/1080	202/18723	1.43e-03	1.50e-02	23
GO:00434912	Breast	Precancer	protein kinase B signaling	23/1080	211/18723	2.53e-03	2.30e-02	23
GO:00158336	Breast	Precancer	peptide transport	27/1080	264/18723	2.84e-03	2.49e-02	27
GO:00347673	Breast	Precancer	positive regulation of ion transmembrane transport	19/1080	167/18723	3.60e-03	2.98e-02	19
GO:00071638	Breast	Precancer	establishment or maintenance of cell polarity	23/1080	218/18723	3.82e-03	3.06e-02	23
GO:00109596	Breast	Precancer	regulation of metal ion transport	37/1080	406/18723	4.07e-03	3.22e-02	37
GO:00020649	Breast	Precancer	epithelial cell development	23/1080	220/18723	4.28e-03	3.35e-02	23
GO:00228985	Breast	Precancer	regulation of transmembrane transporter activity	27/1080	278/18723	5.72e-03	4.11e-02	27
GO:00226049	Breast	Precancer	regulation of cell morphogenesis	29/1080	309/18723	6.88e-03	4.67e-02	29
GO:200123314	Breast	IDC	regulation of apoptotic signaling pathway	82/1434	356/18723	6.27e-20	5.93e-17	82
GO:009719314	Breast	IDC	intrinsic apoptotic signaling pathway	69/1434	288/18723	6.32e-18	2.99e-15	69

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05020	Colorectum	AD	Prion disease	133/2092	273/8465	2.47e-18	8.29e-17	5.29e-17	133
hsa05171	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa04810	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa050201	Colorectum	AD	Prion disease	133/2092	273/8465	2.47e-18	8.29e-17	5.29e-17	133
hsa051711	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa048101	Colorectum	AD	Regulation of actin cytoskeleton	75/2092	229/8465	3.36e-03	1.76e-02	1.12e-02	75
hsa050202	Colorectum	SER	Prion disease	119/1580	273/8465	4.61e-22	3.06e-20	2.22e-20	119
hsa048102	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa050203	Colorectum	SER	Prion disease	119/1580	273/8465	4.61e-22	3.06e-20	2.22e-20	119
hsa048103	Colorectum	SER	Regulation of actin cytoskeleton	60/1580	229/8465	2.74e-03	2.02e-02	1.47e-02	60
hsa050204	Colorectum	MSS	Prion disease	129/1875	273/8465	1.04e-20	5.00e-19	3.06e-19	129
hsa051714	Colorectum	MSS	Coronavirus disease - COVID-19	108/1875	232/8465	6.50e-17	1.67e-15	1.03e-15	108
hsa048104	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68
hsa050205	Colorectum	MSS	Prion disease	129/1875	273/8465	1.04e-20	5.00e-19	3.06e-19	129
hsa051715	Colorectum	MSS	Coronavirus disease - COVID-19	108/1875	232/8465	6.50e-17	1.67e-15	1.03e-15	108
hsa048105	Colorectum	MSS	Regulation of actin cytoskeleton	68/1875	229/8465	4.27e-03	1.86e-02	1.14e-02	68

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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

SNV

Missense_Mutation

c.706N>C

p.Asn236His

p.N236H

P02748

protein_coding

deleterious(0.03)

benign(0.005)

TCGA-A2-A0EW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

SNV

Missense_Mutation

novel

c.1150N>A

p.His384Asn

p.H384N

P02748

protein_coding

tolerated(1)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

novel

c.1483N>C

p.Glu495Gln

p.E495Q

P02748

protein_coding

deleterious(0.03)

probably_damaging(0.989)

TCGA-BH-A0B0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SNV

Missense_Mutation

c.1280C>T

p.Ser427Leu

p.S427L

P02748

protein_coding

deleterious(0.02)

possibly_damaging(0.879)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SNV

Missense_Mutation

c.163N>T

p.Asp55Tyr

p.D55Y

P02748

protein_coding

deleterious(0.02)

probably_damaging(0.996)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

insertion

Frame_Shift_Ins

novel

c.6_7insT

p.Ala3CysfsTer26

p.A3Cfs*26

P02748

protein_coding

TCGA-A2-A04V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

insertion

In_Frame_Ins

novel

c.5_6insCTGGGACTACCATAACAAAGCACCACAAGCTGG

p.Ser2_Ala3insTrpAspTyrHisAsnLysAlaProGlnAlaGly

p.S2_A3insWDYHNKAPQAG

P02748

protein_coding

TCGA-A2-A04V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

deletion

Frame_Shift_Del

c.1481delN

p.Leu494TrpfsTer14

p.L494Wfs*14

P02748

protein_coding

TCGA-AO-A03V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

fluorouracil

insertion

Nonsense_Mutation

novel

c.122_123insGTGAGGATGCTGAGGATGACTGCGGAA

p.Ile41delinsMetTerGlyCysTerGlyTerLeuArgLys

p.I41delinsM*GC*G*LRK

P02748

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

SNV

Missense_Mutation

novel

c.1294G>A

p.Gly432Arg

p.G432R

P02748

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A8XI-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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