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: C6

Gene summary for C6

Gene summary.

Gene information	Species	Human
	Gene symbol	C6
	Gene ID	729
	Gene name	complement C6
	Gene Alias	C6
	Cytomap	5p13.1
	Gene Type	protein-coding
	GO ID	GO:0001701
	UniProtAcc	P13671

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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
729	C6	NAFLD1	Human	Liver	NAFLD	2.68e-11	1.17e+00	-0.04
729	C6	S43	Human	Liver	Cirrhotic	1.89e-08	3.61e-02	-0.0187
729	C6	HCC1_Meng	Human	Liver	HCC	9.17e-29	-5.13e-01	0.0246
729	C6	HCC2_Meng	Human	Liver	HCC	1.09e-10	-5.29e-01	0.0107
729	C6	cirrhotic1	Human	Liver	Cirrhotic	7.08e-14	-3.02e-01	0.0202
729	C6	cirrhotic2	Human	Liver	Cirrhotic	1.54e-20	-1.89e-01	0.0201
729	C6	cirrhotic3	Human	Liver	Cirrhotic	1.26e-10	-2.75e-01	0.0215
729	C6	HCC5	Human	Liver	HCC	1.54e-04	7.50e-01	0.4932
729	C6	Pt13.a	Human	Liver	HCC	1.32e-09	-4.40e-01	0.021
729	C6	Pt13.b	Human	Liver	HCC	4.54e-10	-3.65e-01	0.0251
729	C6	Pt14.d	Human	Liver	HCC	9.20e-09	-4.71e-01	0.0143
729	C6	S014	Human	Liver	HCC	2.49e-03	-5.07e-01	0.2254
729	C6	S015	Human	Liver	HCC	3.42e-03	-5.37e-01	0.2375
729	C6	S016	Human	Liver	HCC	4.74e-11	-5.59e-01	0.2243

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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:00349769	Breast	Precancer	response to endoplasmic reticulum stress	38/1080	256/18723	7.89e-08	4.60e-06	38
GO:00104989	Breast	Precancer	proteasomal protein catabolic process	58/1080	490/18723	1.54e-07	8.05e-06	58
GO:00709725	Breast	Precancer	protein localization to endoplasmic reticulum	15/1080	74/18723	1.74e-05	4.17e-04	15
GO:00431619	Breast	Precancer	proteasome-mediated ubiquitin-dependent protein catabolic process	42/1080	412/18723	2.49e-04	3.72e-03	42
GO:00066059	Breast	Precancer	protein targeting	33/1080	314/18723	6.50e-04	7.99e-03	33
GO:00725948	Breast	Precancer	establishment of protein localization to organelle	41/1080	422/18723	7.75e-04	9.20e-03	41
GO:00718064	Breast	Precancer	protein transmembrane transport	10/1080	59/18723	1.86e-03	1.81e-02	10
GO:00017017	Breast	Precancer	in utero embryonic development	35/1080	367/18723	2.47e-03	2.27e-02	35
GO:00066208	Breast	Precancer	posttranslational protein targeting to endoplasmic reticulum membrane	4/1080	12/18723	3.75e-03	3.04e-02	4
GO:001049814	Breast	IDC	proteasomal protein catabolic process	75/1434	490/18723	5.59e-09	4.41e-07	75
GO:003497614	Breast	IDC	response to endoplasmic reticulum stress	43/1434	256/18723	8.42e-07	3.82e-05	43
GO:007097213	Breast	IDC	protein localization to endoplasmic reticulum	18/1434	74/18723	8.58e-06	2.47e-04	18
GO:004316114	Breast	IDC	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1434	412/18723	9.55e-06	2.68e-04	57
GO:000660514	Breast	IDC	protein targeting	43/1434	314/18723	1.44e-04	2.53e-03	43
GO:007259413	Breast	IDC	establishment of protein localization to organelle	51/1434	422/18723	7.94e-04	9.55e-03	51
GO:007180612	Breast	IDC	protein transmembrane transport	12/1434	59/18723	1.49e-03	1.50e-02	12
GO:000170113	Breast	IDC	in utero embryonic development	42/1434	367/18723	5.85e-03	4.24e-02	42
GO:001049824	Breast	DCIS	proteasomal protein catabolic process	75/1390	490/18723	1.44e-09	1.40e-07	75
GO:003497622	Breast	DCIS	response to endoplasmic reticulum stress	43/1390	256/18723	3.65e-07	1.71e-05	43
GO:004316124	Breast	DCIS	proteasome-mediated ubiquitin-dependent protein catabolic process	57/1390	412/18723	3.76e-06	1.16e-04	57

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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
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
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

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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.201N>C

p.Lys67Asn

p.K67N

P13671

protein_coding

tolerated(0.09)

possibly_damaging(0.717)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

SNV

Missense_Mutation

c.1672G>A

p.Asp558Asn

p.D558N

P13671

protein_coding

tolerated(0.09)

benign(0.29)

TCGA-A8-A09B-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

SNV

Missense_Mutation

c.1375N>G

p.Lys459Glu

p.K459E

P13671

protein_coding

deleterious(0)

probably_damaging(0.934)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

rs369381506

c.1067N>A

p.Arg356Gln

p.R356Q

P13671

protein_coding

tolerated(0.17)

benign(0.098)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

rs763860114

c.2522G>A

p.Arg841His

p.R841H

P13671

protein_coding

tolerated(0.19)

benign(0.35)

TCGA-C8-A12Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

c.311N>T

p.Arg104Ile

p.R104I

P13671

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-E9-A1NA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

SNV

Missense_Mutation

novel

c.1177N>A

p.Glu393Lys

p.E393K

P13671

protein_coding

tolerated(0.24)

benign(0.169)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

insertion

Frame_Shift_Ins

rs762335076

c.828_829insG

p.Ser277GlufsTer15

p.S277Efs*15

P13671

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

deletion

Frame_Shift_Del

rs372345940

c.828delN

p.Ser277AlafsTer43

p.S277Afs*43

P13671

protein_coding

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

insertion

Frame_Shift_Ins

rs762335076

c.828dupG

p.Ser277GlufsTer15

p.S277Efs*15

P13671

protein_coding

TCGA-E9-A1NC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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