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: F7

Gene summary for F7

Gene summary.

Gene information	Species	Human
	Gene symbol	F7
	Gene ID	2155
	Gene name	coagulation factor VII
	Gene Alias	SPCA
	Cytomap	13q34
	Gene Type	protein-coding
	GO ID	GO:0001101
	UniProtAcc	P08709

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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
2155	F7	HCC1_Meng	Human	Liver	HCC	9.89e-73	3.64e-01	0.0246
2155	F7	HCC1	Human	Liver	HCC	1.75e-25	4.37e+00	0.5336
2155	F7	HCC2	Human	Liver	HCC	2.13e-11	3.67e+00	0.5341
2155	F7	Pt14.a	Human	Liver	HCC	1.22e-03	2.45e-01	0.0169
2155	F7	S014	Human	Liver	HCC	2.61e-19	1.05e+00	0.2254
2155	F7	S015	Human	Liver	HCC	2.21e-30	1.78e+00	0.2375
2155	F7	S016	Human	Liver	HCC	2.90e-24	9.09e-01	0.2243
2155	F7	S028	Human	Liver	HCC	9.68e-10	3.41e-01	0.2503
2155	F7	S029	Human	Liver	HCC	1.14e-06	3.03e-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:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00434849	Breast	Precancer	regulation of RNA splicing	34/1080	148/18723	2.66e-12	4.75e-10	34
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00003759	Breast	Precancer	RNA splicing, via transesterification reactions	52/1080	324/18723	1.74e-11	2.22e-09	52
GO:00003779	Breast	Precancer	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00003989	Breast	Precancer	mRNA splicing, via spliceosome	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00480249	Breast	Precancer	regulation of mRNA splicing, via spliceosome	22/1080	101/18723	5.29e-08	3.18e-06	22
GO:19033118	Breast	Precancer	regulation of mRNA metabolic process	38/1080	288/18723	1.63e-06	5.97e-05	38
GO:00506848	Breast	Precancer	regulation of mRNA processing	23/1080	137/18723	3.49e-06	1.13e-04	23
GO:00331199	Breast	Precancer	negative regulation of RNA splicing	9/1080	25/18723	6.03e-06	1.72e-04	9
GO:19033129	Breast	Precancer	negative regulation of mRNA metabolic process	16/1080	92/18723	6.70e-05	1.35e-03	16
GO:00480255	Breast	Precancer	negative regulation of mRNA splicing, via spliceosome	6/1080	20/18723	6.99e-04	8.43e-03	6
GO:00064039	Breast	Precancer	RNA localization	23/1080	201/18723	1.34e-03	1.41e-02	23
GO:19908303	Breast	Precancer	cellular response to leukemia inhibitory factor	13/1080	94/18723	2.83e-03	2.49e-02	13
GO:19908233	Breast	Precancer	response to leukemia inhibitory factor	13/1080	95/18723	3.11e-03	2.64e-02	13
GO:00506865	Breast	Precancer	negative regulation of mRNA processing	6/1080	29/18723	5.49e-03	4.01e-02	6
GO:000838014	Breast	IDC	RNA splicing	73/1434	434/18723	1.27e-10	1.57e-08	73
GO:004348414	Breast	IDC	regulation of RNA splicing	36/1434	148/18723	3.32e-10	3.77e-08	36
GO:000037514	Breast	IDC	RNA splicing, via transesterification reactions	58/1434	324/18723	9.44e-10	9.58e-08	58
GO:000037714	Breast	IDC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1434	320/18723	1.60e-09	1.49e-07	57

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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

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

novel

c.308N>A

p.Ser103Tyr

p.S103Y

P08709

protein_coding

tolerated(0.17)

benign(0.028)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

c.729N>G

p.Ile243Met

p.I243M

P08709

protein_coding

deleterious(0.04)

benign(0.157)

TCGA-AN-A0AM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

novel

c.1132N>A

p.Gly378Arg

p.G378R

P08709

protein_coding

tolerated(0.22)

benign(0)

TCGA-AR-A2LJ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

SNV

Missense_Mutation

rs749760143

c.973N>A

p.Glu325Lys

p.E325K

P08709

protein_coding

tolerated(0.05)

probably_damaging(0.933)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

insertion

Frame_Shift_Ins

novel

c.731_732insGGGAAAATGGGCAGGTCAGC

p.Asn244LysfsTer28

p.N244Kfs*28

P08709

protein_coding

TCGA-AN-A0AM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

insertion

Frame_Shift_Ins

novel

c.757_758insGCAA

p.His253ArgfsTer29

p.H253Rfs*29

P08709

protein_coding

TCGA-BH-A0HY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

taxotere

insertion

In_Frame_Ins

novel

c.759_760insCCCAAGGCCGAATTGTGGGGGGCAAGG

p.His253_Cys254insProLysAlaGluLeuTrpGlyAlaArg

p.H253_C254insPKAELWGAR

P08709

protein_coding

TCGA-BH-A0HY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

taxotere

SNV

Missense_Mutation

c.475N>C

p.Glu159Gln

p.E159Q

P08709

protein_coding

deleterious(0.04)

benign(0.115)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

SNV

Missense_Mutation

novel

c.348N>C

p.Gln116His

p.Q116H

P08709

protein_coding

deleterious(0.02)

probably_damaging(0.961)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SNV

Missense_Mutation

c.160N>A

p.Val54Ile

p.V54I

P08709

protein_coding

tolerated(0.2)

benign(0.01)

TCGA-AA-3811-01

Colorectum

colon adenocarcinoma

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
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE		Vatreptacog alfa (activated)
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE		Factor viia
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE		Recombinant factor VIIa PEGylated liposomal
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE		F-7TG
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE		BAX-817
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE	inhibitor	178103166
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE		CB-813
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE		Activated recombinant FVII-albumin fusion protein
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE	inhibitor	252166701
2155	F7	ENZYME, DRUGGABLE GENOME, PROTEASE		Eptacog alfa intravenous

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