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: FGB

Gene summary for FGB

Gene summary.

Gene information	Species	Human
	Gene symbol	FGB
	Gene ID	2244
	Gene name	fibrinogen beta chain
	Gene Alias	HEL-S-78p
	Cytomap	4q31.3
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P02675

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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
2244	FGB	NAFLD1	Human	Liver	NAFLD	1.93e-11	1.09e+00	-0.04
2244	FGB	S41	Human	Liver	Cirrhotic	1.88e-02	4.12e-01	-0.0343
2244	FGB	S43	Human	Liver	Cirrhotic	4.22e-08	7.15e-01	-0.0187
2244	FGB	HCC1_Meng	Human	Liver	HCC	2.41e-78	5.46e-01	0.0246
2244	FGB	HCC2_Meng	Human	Liver	HCC	5.55e-21	-7.94e-01	0.0107
2244	FGB	cirrhotic1	Human	Liver	Cirrhotic	4.24e-11	-5.56e-01	0.0202
2244	FGB	cirrhotic2	Human	Liver	Cirrhotic	1.05e-12	-2.85e-01	0.0201
2244	FGB	cirrhotic3	Human	Liver	Cirrhotic	8.31e-06	-5.58e-01	0.0215
2244	FGB	HCC1	Human	Liver	HCC	2.06e-30	6.10e+00	0.5336
2244	FGB	HCC2	Human	Liver	HCC	2.70e-44	8.49e+00	0.5341
2244	FGB	HCC5	Human	Liver	HCC	2.86e-02	3.45e+00	0.4932
2244	FGB	Pt13.a	Human	Liver	HCC	8.81e-80	7.72e-01	0.021
2244	FGB	Pt13.b	Human	Liver	HCC	1.41e-102	6.48e-01	0.0251
2244	FGB	Pt13.c	Human	Liver	HCC	6.07e-39	9.33e-01	0.0076
2244	FGB	Pt14.a	Human	Liver	HCC	5.16e-20	5.42e-01	0.0169
2244	FGB	Pt14.b	Human	Liver	HCC	1.36e-28	8.03e-01	0.018
2244	FGB	Pt14.c	Human	Liver	HCC	2.02e-15	8.00e-01	0.0054
2244	FGB	Pt14.d	Human	Liver	HCC	5.12e-47	6.99e-01	0.0143
2244	FGB	S015	Human	Liver	HCC	1.02e-02	1.40e+00	0.2375
2244	FGB	S016	Human	Liver	HCC	3.93e-04	-6.22e-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:190002612	Liver	Cirrhotic	positive regulation of substrate adhesion-dependent cell spreading	23/4634	41/18723	1.75e-05	2.38e-04	23
GO:00301951	Liver	Cirrhotic	negative regulation of blood coagulation	26/4634	49/18723	1.93e-05	2.57e-04	26
GO:19020416	Liver	Cirrhotic	regulation of extrinsic apoptotic signaling pathway via death domain receptors	26/4634	49/18723	1.93e-05	2.57e-04	26
GO:19000471	Liver	Cirrhotic	negative regulation of hemostasis	26/4634	50/18723	3.07e-05	3.84e-04	26
GO:00508191	Liver	Cirrhotic	negative regulation of coagulation	27/4634	53/18723	3.51e-05	4.29e-04	27
GO:000716011	Liver	Cirrhotic	cell-matrix adhesion	85/4634	233/18723	4.06e-05	4.83e-04	85
GO:000759611	Liver	Cirrhotic	blood coagulation	79/4634	217/18723	8.06e-05	8.81e-04	79
GO:00341097	Liver	Cirrhotic	homotypic cell-cell adhesion	39/4634	90/18723	8.57e-05	9.25e-04	39
GO:000759911	Liver	Cirrhotic	hemostasis	80/4634	222/18723	1.08e-04	1.10e-03	80
GO:001077012	Liver	Cirrhotic	positive regulation of cell morphogenesis involved in differentiation	35/4634	79/18723	1.13e-04	1.14e-03	35
GO:005081711	Liver	Cirrhotic	coagulation	79/4634	222/18723	1.90e-04	1.76e-03	79
GO:00457857	Liver	Cirrhotic	positive regulation of cell adhesion	141/4634	437/18723	2.05e-04	1.89e-03	141
GO:00723761	Liver	Cirrhotic	protein activation cascade	9/4634	12/18723	3.59e-04	3.03e-03	9
GO:00107205	Liver	Cirrhotic	positive regulation of cell development	99/4634	298/18723	5.71e-04	4.46e-03	99
GO:19020424	Liver	Cirrhotic	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	16/4634	31/18723	1.15e-03	7.83e-03	16
GO:00705553	Liver	Cirrhotic	response to interleukin-1	52/4634	143/18723	1.27e-03	8.54e-03	52
GO:00610451	Liver	Cirrhotic	negative regulation of wound healing	31/4634	78/18723	2.43e-03	1.46e-02	31
GO:005087812	Liver	Cirrhotic	regulation of body fluid levels	118/4634	379/18723	2.65e-03	1.55e-02	118
GO:19040191	Liver	Cirrhotic	epithelial cell apoptotic process	44/4634	121/18723	2.86e-03	1.65e-02	44
GO:00723781	Liver	Cirrhotic	blood coagulation, fibrin clot formation	7/4634	10/18723	3.29e-03	1.83e-02	7

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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
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
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
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
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
hsa046112	Liver	HCC	Platelet activation	71/4020	124/8465	1.77e-02	4.15e-02	2.31e-02	71
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
hsa0461111	Liver	HCC	Platelet activation	71/4020	124/8465	1.77e-02	4.15e-02	2.31e-02	71

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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

FGB

SNV

Missense_Mutation

c.979N>A

p.Asp327Asn

p.D327N

P02675

protein_coding

deleterious(0)

possibly_damaging(0.753)

TCGA-AO-A1KS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

FGB

SNV

Missense_Mutation

c.1309T>G

p.Cys437Gly

p.C437G

P02675

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-AR-A1AW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

FGB

insertion

Nonsense_Mutation

novel

c.59_60insTTATAGTTTGTGAGATTTTCAGATCTTGTCCTCTTAATTGTAATCCTGTATT

p.Leu20PhefsTer5

p.L20Ffs*5

P02675

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FGB

insertion

Frame_Shift_Ins

novel

c.1365_1366insTGTGTTTGTT

p.Met456CysfsTer11

p.M456Cfs*11

P02675

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FGB

insertion

Frame_Shift_Ins

novel

c.1366_1367insCTTTATAC

p.Met456ThrfsTer13

p.M456Tfs*13

P02675

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FGB

insertion

Frame_Shift_Ins

novel

c.790_791insG

p.Lys264ArgfsTer4

p.K264Rfs*4

P02675

protein_coding

TCGA-BH-A0HX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adrimycin

FGB

insertion

Nonsense_Mutation

novel

c.792_793insTTGGTGACTAAATACAAAGTAATTATGTCATAAAC

p.Pro265LeufsTer11

p.P265Lfs*11

P02675

protein_coding

TCGA-BH-A0HX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adrimycin

FGB

SNV

Missense_Mutation

novel

c.1210N>C

p.Phe404Leu

p.F404L

P02675

protein_coding

tolerated(0.77)

benign(0.018)

TCGA-AA-3984-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

FGB

SNV

Missense_Mutation

c.1086N>T

p.Gln362His

p.Q362H

P02675

protein_coding

tolerated(0.16)

possibly_damaging(0.516)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

FGB

SNV

Missense_Mutation

c.1330N>A

p.Gly444Ser

p.G444S

P02675

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<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
2244	FGB	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, FIBRINOGEN, DRUGGABLE GENOME	inhibitor	CHEMBL1201505	FIBRINOLYSIN, HUMAN
2244	FGB	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, FIBRINOGEN, DRUGGABLE GENOME		RECOMBINANT FACTOR IX FC FUSION PROTEIN
2244	FGB	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, FIBRINOGEN, DRUGGABLE GENOME		HAEMATOXYLIN	HAEMATOXYLIN
2244	FGB	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, FIBRINOGEN, DRUGGABLE GENOME		eptifibatide	EPTIFIBATIDE	20938371
2244	FGB	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, FIBRINOGEN, DRUGGABLE GENOME		ALFIMEPRASE	ALFIMEPRASE
2244	FGB	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, FIBRINOGEN, DRUGGABLE GENOME		abciximab	ABCIXIMAB	20938371
2244	FGB	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, FIBRINOGEN, DRUGGABLE GENOME		tirofiban	TIROFIBAN	20938371
2244	FGB	CELL SURFACE, EXTERNAL SIDE OF PLASMA MEMBRANE, FIBRINOGEN, DRUGGABLE GENOME		METHYLTHIONINIUM CHLORIDE	METHYLTHIONINIUM CHLORIDE

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