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: DACT1

Gene summary for DACT1

Gene summary.

Gene information	Species	Human
	Gene symbol	DACT1
	Gene ID	51339
	Gene name	dishevelled binding antagonist of beta catenin 1
	Gene Alias	DAPPER
	Cytomap	14q23.1
	Gene Type	protein-coding
	GO ID	GO:0000082
	UniProtAcc	Q9NYF0

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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
51339	DACT1	S014	Human	Liver	HCC	5.15e-16	9.18e-01	0.2254
51339	DACT1	S015	Human	Liver	HCC	3.20e-05	6.49e-01	0.2375
51339	DACT1	S016	Human	Liver	HCC	4.45e-15	8.79e-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:000989622	Liver	HCC	positive regulation of catabolic process	335/7958	492/18723	3.83e-31	1.87e-28	335
GO:003133122	Liver	HCC	positive regulation of cellular catabolic process	295/7958	427/18723	3.20e-29	1.45e-26	295
GO:004217622	Liver	HCC	regulation of protein catabolic process	267/7958	391/18723	2.45e-25	7.38e-23	267
GO:003164722	Liver	HCC	regulation of protein stability	211/7958	298/18723	2.29e-23	5.01e-21	211
GO:190336222	Liver	HCC	regulation of cellular protein catabolic process	182/7958	255/18723	5.91e-21	8.52e-19	182
GO:004573222	Liver	HCC	positive regulation of protein catabolic process	163/7958	231/18723	4.00e-18	4.69e-16	163
GO:004325422	Liver	HCC	regulation of protein-containing complex assembly	264/7958	428/18723	5.47e-16	4.39e-14	264
GO:190336422	Liver	HCC	positive regulation of cellular protein catabolic process	115/7958	155/18723	9.30e-16	7.19e-14	115
GO:005109822	Liver	HCC	regulation of binding	225/7958	363/18723	3.78e-14	2.37e-12	225
GO:004339322	Liver	HCC	regulation of protein binding	129/7958	196/18723	3.27e-11	1.26e-09	129
GO:00447722	Liver	HCC	mitotic cell cycle phase transition	240/7958	424/18723	2.47e-09	6.84e-08	240
GO:000734611	Liver	HCC	regulation of mitotic cell cycle	255/7958	457/18723	4.96e-09	1.30e-07	255
GO:019873821	Liver	HCC	cell-cell signaling by wnt	247/7958	446/18723	2.11e-08	4.96e-07	247
GO:001605521	Liver	HCC	Wnt signaling pathway	245/7958	444/18723	3.68e-08	8.09e-07	245
GO:005109922	Liver	HCC	positive regulation of binding	108/7958	173/18723	9.22e-08	1.83e-06	108
GO:003133312	Liver	HCC	negative regulation of protein-containing complex assembly	91/7958	141/18723	1.01e-07	1.98e-06	91
GO:003209221	Liver	HCC	positive regulation of protein binding	59/7958	85/18723	4.66e-07	7.61e-06	59
GO:19019901	Liver	HCC	regulation of mitotic cell cycle phase transition	167/7958	299/18723	1.96e-06	2.71e-05	167
GO:19019871	Liver	HCC	regulation of cell cycle phase transition	211/7958	390/18723	2.11e-06	2.89e-05	211
GO:003011121	Liver	HCC	regulation of Wnt signaling pathway	180/7958	328/18723	3.62e-06	4.72e-05	180

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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

DACT1

SNV

Missense_Mutation

c.1154N>T

p.Ser385Leu

p.S385L

Q9NYF0

protein_coding

tolerated(0.19)

benign(0.178)

TCGA-C8-A274-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

DACT1

SNV

Missense_Mutation

c.1073N>T

p.Pro358Leu

p.P358L

Q9NYF0

protein_coding

deleterious(0.04)

benign(0.092)

TCGA-E9-A1NE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DACT1

SNV

Missense_Mutation

novel

c.961C>T

p.Pro321Ser

p.P321S

Q9NYF0

protein_coding

tolerated(0.1)

possibly_damaging(0.643)

TCGA-E9-A6HE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

DACT1

insertion

Nonsense_Mutation

novel

c.1655_1656insCCTCTGAGGGAAGAGGACAG

p.His553LeufsTer2

p.H553Lfs*2

Q9NYF0

protein_coding

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

DACT1

insertion

In_Frame_Ins

novel

c.1657_1658insTTGGAA

p.His553delinsLeuGlyAsn

p.H553delinsLGN

Q9NYF0

protein_coding

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

DACT1

insertion

Nonsense_Mutation

novel

c.1880_1881insTCACAGGGCAACAGTGTGAACCTTAAGAATTCGAAA

p.Ala627_Ser628insHisArgAlaThrValTerThrLeuArgIleArgAsn

p.A627_S628insHRATV*TLRIRN

Q9NYF0

protein_coding

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

DACT1

SNV

Missense_Mutation

rs767249134

c.359N>A

p.Arg120Gln

p.R120Q

Q9NYF0

protein_coding

deleterious(0)

probably_damaging(0.913)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DACT1

SNV

Missense_Mutation

novel

c.1721N>T

p.Arg574Met

p.R574M

Q9NYF0

protein_coding

deleterious(0)

possibly_damaging(0.708)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DACT1

SNV

Missense_Mutation

rs368345387

c.2138N>G

p.Tyr713Cys

p.Y713C

Q9NYF0

protein_coding

deleterious(0.01)

possibly_damaging(0.891)

TCGA-C5-A1ML-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DACT1

SNV

Missense_Mutation

c.691G>A

p.Ala231Thr

p.A231T

Q9NYF0

protein_coding

tolerated(1)

benign(0)

TCGA-FU-A3EO-01

Cervix

cervical & endocervical cancer

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

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