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: C7

Gene summary for C7

Gene summary.

Gene information	Species	Human
	Gene symbol	C7
	Gene ID	730
	Gene name	complement C7
	Gene Alias	C7
	Cytomap	5p13.1
	Gene Type	protein-coding
	GO ID	GO:0002250
	UniProtAcc	P10643

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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
730	C7	S41	Human	Liver	Cirrhotic	1.84e-05	9.56e-01	-0.0343
730	C7	S43	Human	Liver	Cirrhotic	8.05e-08	7.04e-01	-0.0187
730	C7	cirrhotic3	Human	Liver	Cirrhotic	3.02e-16	5.44e-01	0.0215
730	C7	HCC1	Human	Liver	HCC	4.11e-03	2.49e-01	0.5336

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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:00004694	Skin	cSCC	cleavage involved in rRNA processing	19/4864	27/18723	1.72e-06	2.88e-05	19
GO:190199114	Skin	cSCC	negative regulation of mitotic cell cycle phase transition	75/4864	179/18723	2.38e-06	3.84e-05	75
GO:004593014	Skin	cSCC	negative regulation of mitotic cell cycle	93/4864	235/18723	3.14e-06	4.89e-05	93
GO:00335235	Skin	cSCC	histone H2B ubiquitination	11/4864	12/18723	3.30e-06	5.08e-05	11
GO:00063784	Skin	cSCC	mRNA polyadenylation	26/4864	44/18723	3.48e-06	5.29e-05	26
GO:004578613	Skin	cSCC	negative regulation of cell cycle	140/4864	385/18723	3.64e-06	5.50e-05	140
GO:001605524	Skin	cSCC	Wnt signaling pathway	158/4864	444/18723	3.80e-06	5.70e-05	158
GO:00314405	Skin	cSCC	regulation of mRNA 3'-end processing	19/4864	28/18723	4.03e-06	6.04e-05	19
GO:001982715	Skin	cSCC	stem cell population maintenance	58/4864	131/18723	4.20e-06	6.24e-05	58
GO:001657415	Skin	cSCC	histone ubiquitination	27/4864	47/18723	4.79e-06	7.03e-05	27
GO:019873824	Skin	cSCC	cell-cell signaling by wnt	158/4864	446/18723	5.08e-06	7.38e-05	158
GO:00450484	Skin	cSCC	protein insertion into ER membrane	16/4864	22/18723	5.92e-06	8.44e-05	16
GO:00436314	Skin	cSCC	RNA polyadenylation	26/4864	45/18723	6.20e-06	8.78e-05	26
GO:00070296	Skin	cSCC	endoplasmic reticulum organization	42/4864	87/18723	6.36e-06	8.92e-05	42
GO:003424915	Skin	cSCC	negative regulation of cellular amide metabolic process	104/4864	273/18723	6.44e-06	9.00e-05	104
GO:000008222	Skin	cSCC	G1/S transition of mitotic cell cycle	85/4864	214/18723	6.90e-06	9.60e-05	85
GO:009006815	Skin	cSCC	positive regulation of cell cycle process	92/4864	236/18723	7.33e-06	1.01e-04	92
GO:00709795	Skin	cSCC	protein K11-linked ubiquitination	19/4864	29/18723	8.84e-06	1.17e-04	19
GO:009872715	Skin	cSCC	maintenance of cell number	58/4864	134/18723	9.83e-06	1.29e-04	58
GO:00718164	Skin	cSCC	tail-anchored membrane protein insertion into ER membrane	13/4864	17/18723	1.92e-05	2.27e-04	13

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517122	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
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
hsa0517132	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
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
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
hsa046104	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57
hsa0481041	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134
hsa0502032	Liver	HCC	Prion disease	195/4020	273/8465	3.26e-16	1.56e-14	8.67e-15	195
hsa0517152	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa046105	Liver	HCC	Complement and coagulation cascades	57/4020	86/8465	3.19e-04	1.45e-03	8.04e-04	57
hsa0481051	Liver	HCC	Regulation of actin cytoskeleton	134/4020	229/8465	4.48e-04	1.94e-03	1.08e-03	134

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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.2353N>C

p.Glu785Gln

p.E785Q

P10643

protein_coding

tolerated(1)

benign(0)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SNV

Missense_Mutation

c.320C>T

p.Ser107Phe

p.S107F

P10643

protein_coding

tolerated(0.21)

possibly_damaging(0.77)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

SNV

Missense_Mutation

rs376674018

c.148N>T

p.Arg50Trp

p.R50W

P10643

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

SNV

Missense_Mutation

c.1639N>C

p.Asp547His

p.D547H

P10643

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-C8-A12P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

c.2037G>C

p.Trp679Cys

p.W679C

P10643

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

c.944T>C

p.Val315Ala

p.V315A

P10643

protein_coding

tolerated(0.31)

benign(0.207)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

SNV

Missense_Mutation

rs766182545

c.2353N>A

p.Glu785Lys

p.E785K

P10643

protein_coding

tolerated(0.07)

benign(0.003)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

novel

c.2451N>T

p.Glu817Asp

p.E817D

P10643

protein_coding

deleterious(0.01)

probably_damaging(0.971)

TCGA-GI-A2C9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

insertion

Frame_Shift_Ins

novel

c.1744_1745insGCATTAATCAGTATCTCTTGACTGAGGAAGC

p.Val582GlyfsTer14

p.V582Gfs*14

P10643

protein_coding

TCGA-AN-A0FV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

insertion

In_Frame_Ins

novel

c.2350_2350+1insCTCTGA

p.Ala784_Glu785insLeuThr

p.A784_E785insLT

P10643

protein_coding

TCGA-AR-A0U0-01

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

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