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: F2

Gene summary for F2

Gene summary.

Gene information	Species	Human
	Gene symbol	F2
	Gene ID	2147
	Gene name	coagulation factor II, thrombin
	Gene Alias	PT
	Cytomap	11p11.2
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	P00734

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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
2147	F2	NAFLD1	Human	Liver	NAFLD	9.89e-14	7.90e-01	-0.04
2147	F2	S42	Human	Liver	HCC	2.13e-05	8.38e-01	-0.0103
2147	F2	S43	Human	Liver	Cirrhotic	2.49e-07	1.05e-01	-0.0187
2147	F2	HCC1_Meng	Human	Liver	HCC	1.04e-80	9.88e-01	0.0246
2147	F2	HCC2_Meng	Human	Liver	HCC	4.95e-09	-2.59e-01	0.0107
2147	F2	HCC1	Human	Liver	HCC	1.98e-25	5.00e+00	0.5336
2147	F2	HCC2	Human	Liver	HCC	3.09e-51	6.34e+00	0.5341
2147	F2	HCC5	Human	Liver	HCC	8.60e-04	3.95e+00	0.4932
2147	F2	Pt13.a	Human	Liver	HCC	5.10e-04	2.62e-01	0.021
2147	F2	Pt13.b	Human	Liver	HCC	1.18e-26	3.65e-01	0.0251
2147	F2	Pt14.a	Human	Liver	HCC	5.50e-13	8.94e-01	0.0169
2147	F2	Pt14.b	Human	Liver	HCC	5.18e-12	6.44e-01	0.018
2147	F2	Pt14.d	Human	Liver	HCC	2.29e-05	4.93e-01	0.0143
2147	F2	S014	Human	Liver	HCC	1.99e-50	3.29e+00	0.2254
2147	F2	S015	Human	Liver	HCC	3.05e-52	3.52e+00	0.2375
2147	F2	S016	Human	Liver	HCC	3.24e-50	3.13e+00	0.2243
2147	F2	S027	Human	Liver	HCC	1.75e-27	2.39e+00	0.2446
2147	F2	S028	Human	Liver	HCC	6.56e-57	2.58e+00	0.2503
2147	F2	S029	Human	Liver	HCC	5.93e-59	3.06e+00	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:00021819	Breast	Precancer	cytoplasmic translation	80/1080	148/18723	1.59e-59	8.54e-56	80
GO:00226139	Breast	Precancer	ribonucleoprotein complex biogenesis	79/1080	463/18723	2.11e-18	1.03e-15	79
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:00422549	Breast	Precancer	ribosome biogenesis	52/1080	299/18723	7.35e-13	1.51e-10	52
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:00457279	Breast	Precancer	positive regulation of translation	32/1080	136/18723	5.89e-12	9.27e-10	32
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:00342509	Breast	Precancer	positive regulation of cellular amide metabolic process	33/1080	162/18723	1.72e-10	1.77e-08	33
GO:00422749	Breast	Precancer	ribosomal small subunit biogenesis	21/1080	73/18723	4.84e-10	4.39e-08	21
GO:00064588	Breast	Precancer	'de novo' protein folding	16/1080	43/18723	8.14e-10	6.92e-08	16
GO:00003029	Breast	Precancer	response to reactive oxygen species	38/1080	222/18723	1.47e-09	1.23e-07	38
GO:00610778	Breast	Precancer	chaperone-mediated protein folding	19/1080	67/18723	4.22e-09	3.28e-07	19
GO:00510848	Breast	Precancer	'de novo' posttranslational protein folding	14/1080	39/18723	1.61e-08	1.12e-06	14
GO:00510858	Breast	Precancer	chaperone cofactor-dependent protein refolding	13/1080	34/18723	2.17e-08	1.47e-06	13
GO:00359669	Breast	Precancer	response to topologically incorrect protein	29/1080	159/18723	3.00e-08	1.89e-06	29

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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
hsa0513014	Liver	NAFLD	Pathogenic Escherichia coli infection	45/1043	197/8465	2.31e-05	6.88e-04	5.54e-04	45
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
hsa0513015	Liver	NAFLD	Pathogenic Escherichia coli infection	45/1043	197/8465	2.31e-05	6.88e-04	5.54e-04	45
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
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
hsa0513022	Liver	Cirrhotic	Pathogenic Escherichia coli infection	88/2530	197/8465	6.48e-06	6.24e-05	3.84e-05	88
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
hsa0513032	Liver	Cirrhotic	Pathogenic Escherichia coli infection	88/2530	197/8465	6.48e-06	6.24e-05	3.84e-05	88
hsa0517142	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa0513042	Liver	HCC	Pathogenic Escherichia coli infection	129/4020	197/8465	2.02e-07	2.50e-06	1.39e-06	129
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

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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
GZMA	F2R	GZMA_F2R	PARs	Breast	ADJ
GZMA	F2RL2	GZMA_F2RL2	PARs	Breast	ADJ
GZMA	F2R	GZMA_F2R	PARs	Breast	DCIS
CTSG	F2RL3	CTSG_F2RL3	PARs	Breast	Healthy
GZMA	F2RL3	GZMA_F2RL3	PARs	Breast	Healthy
GZMA	F2R	GZMA_F2R	PARs	Breast	IDC
CTSG	F2R	CTSG_F2R	PARs	Cervix	ADJ
GZMA	F2R	GZMA_F2R	PARs	Cervix	ADJ
PRSS3	F2R	PRSS3_F2R	PARs	Cervix	CC
CTSG	F2R	CTSG_F2R	PARs	Cervix	CC
GZMA	F2R	GZMA_F2R	PARs	Cervix	CC
GZMA	F2R	GZMA_F2R	PARs	Cervix	Healthy
CTSG	F2R	CTSG_F2R	PARs	Cervix	Precancer
GZMA	F2R	GZMA_F2R	PARs	Cervix	Precancer
PRSS3	F2R	PRSS3_F2R	PARs	CRC	AD
CTSG	F2R	CTSG_F2R	PARs	CRC	AD
GZMA	F2R	GZMA_F2R	PARs	CRC	AD
PRSS3	F2RL3	PRSS3_F2RL3	PARs	CRC	AD
CTSG	F2RL3	CTSG_F2RL3	PARs	CRC	AD
GZMA	F2RL3	GZMA_F2RL3	PARs	CRC	AD

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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.1390N>T

p.Ala464Ser

p.A464S

P00734

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B6-A0RL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SNV

Missense_Mutation

rs121918482

c.1292N>A

p.Arg431His

p.R431H

P00734

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SNV

Missense_Mutation

c.448N>T

p.Ala150Ser

p.A150S

P00734

protein_coding

tolerated(0.47)

benign(0.06)

TCGA-E2-A15S-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

insertion

In_Frame_Ins

novel

c.1074_1075insACCCAGCATGAGCTTTCCTGGGATTACTCATAT

p.Ser358_Tyr359insThrGlnHisGluLeuSerTrpAspTyrSerTyr

p.S358_Y359insTQHELSWDYSY

P00734

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

deletion

Frame_Shift_Del

c.1015_1025delNNNNNNNNNNN

p.Pro340GlufsTer55

p.P340Efs*55

P00734

protein_coding

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

deletion

Frame_Shift_Del

novel

c.204delN

p.Glu69ArgfsTer52

p.E69Rfs*52

P00734

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

SNV

Missense_Mutation

rs144785536

c.103C>T

p.Arg35Trp

p.R35W

P00734

protein_coding

tolerated(0.11)

benign(0.093)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SNV

Missense_Mutation

novel

c.1755N>T

p.Met585Ile

p.M585I

P00734

protein_coding

tolerated(0.47)

benign(0.011)

TCGA-EK-A2RE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SNV

Missense_Mutation

novel

c.225N>C

p.Glu75Asp

p.E75D

P00734

protein_coding

deleterious(0.01)

probably_damaging(0.987)

TCGA-VS-A953-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SNV

Missense_Mutation

rs775306348

c.5C>T

p.Ala2Val

p.A2V

P00734

protein_coding

tolerated_low_confidence(0.14)

benign(0.01)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

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
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		Anisindione	ANISINDIONE
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		LEPIRUDIN	LEPIRUDIN
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		ATryn antithrombin		24391399
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		(-)-EPICATECHIN	(-)-EPICATECHIN
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		hormonal contraceptives for systemic use		15208046,28750087,12069454,16769590
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		Odiparcil	ODIPARCIL
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		QUERCETIN	QUERCETIN
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		AZD-0837	ATECEGATRAN METOXIL
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME		Hirudin
2147	F2	PROTEASE, EXTERNAL SIDE OF PLASMA MEMBRANE, GROWTH FACTOR, DRUGGABLE GENOME, ENZYME	inhibitor	178102998	DABIGATRAN

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