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: ADAMTS18

Gene summary for ADAMTS18

Gene summary.

Gene information	Species	Human
	Gene symbol	ADAMTS18
	Gene ID	170692
	Gene name	ADAM metallopeptidase with thrombospondin type 1 motif 18
	Gene Alias	ADAMTS21
	Cytomap	16q23.1
	Gene Type	protein-coding
	GO ID	GO:0001654
	UniProtAcc	Q2VYF7

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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
170692	ADAMTS18	S014	Human	Liver	HCC	4.12e-18	5.96e-01	0.2254
170692	ADAMTS18	S015	Human	Liver	HCC	2.68e-22	9.39e-01	0.2375
170692	ADAMTS18	S016	Human	Liver	HCC	6.12e-28	8.13e-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:00301932	Liver	HCC	regulation of blood coagulation	46/7958	66/18723	7.12e-06	8.47e-05	46
GO:19000462	Liver	HCC	regulation of hemostasis	46/7958	68/18723	2.43e-05	2.56e-04	46
GO:00508182	Liver	HCC	regulation of coagulation	47/7958	71/18723	4.68e-05	4.50e-04	47
GO:004206022	Liver	HCC	wound healing	219/7958	422/18723	5.34e-05	5.04e-04	219
GO:006104122	Liver	HCC	regulation of wound healing	78/7958	134/18723	1.73e-04	1.36e-03	78
GO:190303421	Liver	HCC	regulation of response to wounding	94/7958	167/18723	2.19e-04	1.66e-03	94
GO:00075962	Liver	HCC	blood coagulation	118/7958	217/18723	2.63e-04	1.94e-03	118
GO:003410912	Liver	HCC	homotypic cell-cell adhesion	55/7958	90/18723	2.81e-04	2.02e-03	55
GO:00301952	Liver	HCC	negative regulation of blood coagulation	33/7958	49/18723	3.86e-04	2.62e-03	33
GO:00075992	Liver	HCC	hemostasis	119/7958	222/18723	5.25e-04	3.41e-03	119
GO:19000472	Liver	HCC	negative regulation of hemostasis	33/7958	50/18723	6.74e-04	4.15e-03	33
GO:00508172	Liver	HCC	coagulation	118/7958	222/18723	8.41e-04	5.03e-03	118
GO:005087822	Liver	HCC	regulation of body fluid levels	191/7958	379/18723	1.06e-03	6.11e-03	191
GO:00508192	Liver	HCC	negative regulation of coagulation	34/7958	53/18723	1.20e-03	6.68e-03	34
GO:007052712	Liver	HCC	platelet aggregation	40/7958	67/18723	3.35e-03	1.53e-02	40
GO:00341102	Liver	HCC	regulation of homotypic cell-cell adhesion	22/7958	33/18723	4.38e-03	1.90e-02	22
GO:0034111	Liver	HCC	negative regulation of homotypic cell-cell adhesion	11/7958	14/18723	6.81e-03	2.73e-02	11

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

ADAMTS18

SNV

Missense_Mutation

novel

c.3381G>T

p.Trp1127Cys

p.W1127C

Q8TE60

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

ADAMTS18

SNV

Missense_Mutation

rs372966603

c.2627A>T

p.Tyr876Phe

p.Y876F

Q8TE60

protein_coding

tolerated(0.12)

benign(0.02)

TCGA-AO-A0JM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ADAMTS18

SNV

Missense_Mutation

c.3472T>G

p.Ser1158Ala

p.S1158A

Q8TE60

protein_coding

tolerated(0.51)

benign(0.007)

TCGA-AR-A0TV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADAMTS18

SNV

Missense_Mutation

c.1684N>A

p.Glu562Lys

p.E562K

Q8TE60

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

ADAMTS18

insertion

In_Frame_Ins

novel

c.899_900insAAAAACCTTCAACTTGGCTAAGTCAACAGCTTTGACCAAGCAAAC

p.Val300_Ala301insLysThrPheAsnLeuAlaLysSerThrAlaLeuThrLysGlnThr

p.V300_A301insKTFNLAKSTALTKQT

Q8TE60

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ADAMTS18

insertion

In_Frame_Ins

novel

c.3041_3042insCACTCT

p.Arg1014_Glu1015insThrLeu

p.R1014_E1015insTL

Q8TE60

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ADAMTS18

insertion

Frame_Shift_Ins

novel

c.3040_3041insCAAGTCACCAAGCACCTTATATACCTCCA

p.Arg1014ProfsTer69

p.R1014Pfs*69

Q8TE60

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ADAMTS18

insertion

In_Frame_Ins

novel

c.2962_2963insTGTTACCTCCTGTGTGTGAGAGGT

p.Ser988delinsMetLeuProProValCysGluArgCys

p.S988delinsMLPPVCERC

Q8TE60

protein_coding

TCGA-B6-A0IE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

ADAMTS18

SNV

Missense_Mutation

novel

c.2324G>A

p.Arg775Gln

p.R775Q

Q8TE60

protein_coding

tolerated(0.09)

possibly_damaging(0.642)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ADAMTS18

SNV

Missense_Mutation

rs558792154

c.361C>G

p.His121Asp

p.H121D

Q8TE60

protein_coding

tolerated(0.07)

benign(0.033)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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