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: KNG1

Gene summary for KNG1

Gene summary.

Gene information	Species	Human
	Gene symbol	KNG1
	Gene ID	3827
	Gene name	kininogen 1
	Gene Alias	BDK
	Cytomap	3q27.3
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	P01042

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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
3827	KNG1	NAFLD1	Human	Liver	NAFLD	1.73e-11	8.50e-01	-0.04
3827	KNG1	S42	Human	Liver	HCC	1.91e-03	7.98e-01	-0.0103
3827	KNG1	S43	Human	Liver	Cirrhotic	3.07e-04	-3.11e-02	-0.0187
3827	KNG1	HCC1_Meng	Human	Liver	HCC	3.95e-78	4.13e-01	0.0246
3827	KNG1	HCC2_Meng	Human	Liver	HCC	1.38e-16	-4.86e-01	0.0107
3827	KNG1	HCC1	Human	Liver	HCC	9.38e-42	6.55e+00	0.5336
3827	KNG1	HCC2	Human	Liver	HCC	1.35e-51	6.53e+00	0.5341
3827	KNG1	HCC5	Human	Liver	HCC	1.30e-07	3.91e+00	0.4932
3827	KNG1	Pt13.a	Human	Liver	HCC	5.24e-10	2.42e-01	0.021
3827	KNG1	Pt13.b	Human	Liver	HCC	6.34e-33	1.72e-01	0.0251
3827	KNG1	Pt14.a	Human	Liver	HCC	1.06e-05	1.84e-01	0.0169
3827	KNG1	Pt14.b	Human	Liver	HCC	6.02e-26	7.69e-01	0.018
3827	KNG1	Pt14.c	Human	Liver	HCC	8.86e-06	7.74e-01	0.0054
3827	KNG1	Pt14.d	Human	Liver	HCC	1.34e-16	6.34e-01	0.0143
3827	KNG1	S015	Human	Liver	HCC	3.00e-02	-4.81e-01	0.2375
3827	KNG1	S016	Human	Liver	HCC	6.10e-09	-4.92e-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:00610417	Liver	NAFLD	regulation of wound healing	39/1882	134/18723	5.52e-10	1.28e-07	39
GO:00420607	Liver	NAFLD	wound healing	84/1882	422/18723	6.56e-10	1.37e-07	84
GO:0030195	Liver	NAFLD	negative regulation of blood coagulation	21/1882	49/18723	2.42e-09	4.05e-07	21
GO:1900047	Liver	NAFLD	negative regulation of hemostasis	21/1882	50/18723	3.78e-09	5.40e-07	21
GO:0030193	Liver	NAFLD	regulation of blood coagulation	24/1882	66/18723	9.30e-09	1.26e-06	24
GO:0050819	Liver	NAFLD	negative regulation of coagulation	21/1882	53/18723	1.33e-08	1.69e-06	21
GO:1900046	Liver	NAFLD	regulation of hemostasis	24/1882	68/18723	1.84e-08	2.09e-06	24
GO:0061045	Liver	NAFLD	negative regulation of wound healing	26/1882	78/18723	1.86e-08	2.09e-06	26
GO:19030347	Liver	NAFLD	regulation of response to wounding	41/1882	167/18723	4.70e-08	4.58e-06	41
GO:0050818	Liver	NAFLD	regulation of coagulation	24/1882	71/18723	4.80e-08	4.60e-06	24
GO:00075994	Liver	NAFLD	hemostasis	49/1882	222/18723	9.23e-08	7.59e-06	49
GO:00075964	Liver	NAFLD	blood coagulation	48/1882	217/18723	1.16e-07	8.81e-06	48
GO:00508174	Liver	NAFLD	coagulation	48/1882	222/18723	2.40e-07	1.61e-05	48
GO:00458617	Liver	NAFLD	negative regulation of proteolysis	66/1882	351/18723	4.02e-07	2.58e-05	66
GO:1903035	Liver	NAFLD	negative regulation of response to wounding	26/1882	94/18723	1.18e-06	5.66e-05	26
GO:00513467	Liver	NAFLD	negative regulation of hydrolase activity	62/1882	379/18723	8.11e-05	1.66e-03	62
GO:00525477	Liver	NAFLD	regulation of peptidase activity	72/1882	461/18723	1.03e-04	2.03e-03	72
GO:00030182	Liver	NAFLD	vascular process in circulatory system	46/1882	263/18723	1.36e-04	2.58e-03	46
GO:00525487	Liver	NAFLD	regulation of endopeptidase activity	67/1882	432/18723	2.17e-04	3.70e-03	67
GO:00508787	Liver	NAFLD	regulation of body fluid levels	60/1882	379/18723	2.61e-04	4.23e-03	60

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
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
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
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
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
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
hsa05142	Liver	HCC	Chagas disease	61/4020	102/8465	8.04e-03	2.17e-02	1.21e-02	61
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
hsa051421	Liver	HCC	Chagas disease	61/4020	102/8465	8.04e-03	2.17e-02	1.21e-02	61

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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

KNG1

SNV

Missense_Mutation

novel

c.1822G>A

p.Asp608Asn

p.D608N

P01042

protein_coding

deleterious(0)

benign(0.073)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

KNG1

SNV

Missense_Mutation

c.1114C>T

p.Pro372Ser

p.P372S

P01042

protein_coding

tolerated(0.86)

benign(0.001)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KNG1

SNV

Missense_Mutation

rs752033867

c.902N>C

p.Ile301Thr

p.I301T

P01042

protein_coding

tolerated(0.1)

benign(0.114)

TCGA-AR-A1AR-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

Docetaxel

KNG1

SNV

Missense_Mutation

c.1670C>T

p.Thr557Ile

p.T557I

P01042

protein_coding

tolerated(0.07)

benign(0.001)

TCGA-BH-A0BP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

KNG1

SNV

Missense_Mutation

c.1693N>A

p.Asp565Asn

p.D565N

P01042

protein_coding

tolerated(0.09)

benign(0.092)

TCGA-GI-A2C8-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

Adriamycin

KNG1

insertion

In_Frame_Ins

novel

c.91_92insTCCACCCTGGGAGCAATTTTCTTTTAC

p.Lys31delinsIleHisProGlySerAsnPheLeuLeuGln

p.K31delinsIHPGSNFLLQ

P01042

protein_coding

TCGA-BH-A0HY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

taxotere

KNG1

SNV

Missense_Mutation

novel

c.308C>T

p.Ala103Val

p.A103V

P01042

protein_coding

deleterious(0.02)

possibly_damaging(0.812)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

KNG1

SNV

Missense_Mutation

novel

c.1417N>T

p.His473Tyr

p.H473Y

P01042

protein_coding

tolerated(0.08)

benign(0.006)

TCGA-A6-2672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

KNG1

SNV

Missense_Mutation

c.1702N>T

p.Leu568Phe

p.L568F

P01042

protein_coding

tolerated(0.11)

benign(0.017)

TCGA-AA-3510-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

KNG1

SNV

Missense_Mutation

novel

c.509N>C

p.Asn170Thr

p.N170T

P01042

protein_coding

deleterious(0.01)

benign(0.139)

TCGA-AA-3947-01

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
3827	KNG1	DRUGGABLE GENOME, PROTEASE INHIBITOR		hormonal contraceptives for systemic use		28750087
3827	KNG1	DRUGGABLE GENOME, PROTEASE INHIBITOR		Avoralstat	AVORALSTAT

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