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: DAP

Gene summary for DAP

Gene summary.

Gene information	Species	Human
	Gene symbol	DAP
	Gene ID	1611
	Gene name	death associated protein
	Gene Alias	DAP
	Cytomap	5p15.2
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	B4DQ75

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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
1611	DAP	HTA11_1938_2000001011	Human	Colorectum	AD	6.63e-04	4.68e-01	-0.0811
1611	DAP	HTA11_78_2000001011	Human	Colorectum	AD	4.65e-02	4.43e-01	-0.1088
1611	DAP	HTA11_347_2000001011	Human	Colorectum	AD	6.08e-10	4.85e-01	-0.1954
1611	DAP	HTA11_411_2000001011	Human	Colorectum	SER	2.17e-04	1.04e+00	-0.2602
1611	DAP	HTA11_696_2000001011	Human	Colorectum	AD	3.14e-09	5.69e-01	-0.1464
1611	DAP	HTA11_1391_2000001011	Human	Colorectum	AD	2.60e-10	6.78e-01	-0.059
1611	DAP	HTA11_6818_2000001021	Human	Colorectum	AD	1.29e-02	4.87e-01	0.0588
1611	DAP	HTA11_99999971662_82457	Human	Colorectum	MSS	1.20e-02	5.68e-01	0.3859
1611	DAP	A015-C-203	Human	Colorectum	FAP	1.36e-21	-3.63e-01	-0.1294
1611	DAP	A015-C-204	Human	Colorectum	FAP	2.43e-02	-1.60e-01	-0.0228
1611	DAP	A002-C-201	Human	Colorectum	FAP	2.02e-07	-2.83e-01	0.0324
1611	DAP	A002-C-203	Human	Colorectum	FAP	2.61e-05	-1.44e-01	0.2786
1611	DAP	A001-C-119	Human	Colorectum	FAP	4.00e-03	-2.73e-01	-0.1557
1611	DAP	A001-C-108	Human	Colorectum	FAP	1.29e-12	-2.62e-01	-0.0272
1611	DAP	A002-C-205	Human	Colorectum	FAP	5.28e-11	-2.68e-01	-0.1236
1611	DAP	A015-C-006	Human	Colorectum	FAP	3.56e-08	-3.31e-01	-0.0994
1611	DAP	A015-C-106	Human	Colorectum	FAP	1.60e-08	-2.54e-01	-0.0511
1611	DAP	A002-C-114	Human	Colorectum	FAP	2.27e-10	-3.64e-01	-0.1561
1611	DAP	A015-C-104	Human	Colorectum	FAP	6.12e-20	-3.78e-01	-0.1899
1611	DAP	A001-C-014	Human	Colorectum	FAP	2.06e-11	-2.16e-01	0.0135

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:000704425	Skin	cSCC	cell-substrate junction assembly	48/4864	95/18723	2.57e-07	5.33e-06	48
GO:200123628	Skin	cSCC	regulation of extrinsic apoptotic signaling pathway	68/4864	151/18723	3.01e-07	6.12e-06	68
GO:009719128	Skin	cSCC	extrinsic apoptotic signaling pathway	91/4864	219/18723	3.31e-07	6.63e-06	91
GO:015011625	Skin	cSCC	regulation of cell-substrate junction organization	37/4864	71/18723	2.28e-06	3.70e-05	37
GO:001605524	Skin	cSCC	Wnt signaling pathway	158/4864	444/18723	3.80e-06	5.70e-05	158
GO:000195224	Skin	cSCC	regulation of cell-matrix adhesion	57/4864	128/18723	4.07e-06	6.07e-05	57
GO:001081027	Skin	cSCC	regulation of cell-substrate adhesion	88/4864	221/18723	4.26e-06	6.32e-05	88
GO:000632519	Skin	cSCC	chromatin organization	147/4864	409/18723	4.41e-06	6.52e-05	147
GO:0010950112	Skin	cSCC	positive regulation of endopeptidase activity	74/4864	179/18723	4.98e-06	7.25e-05	74
GO:019873824	Skin	cSCC	cell-cell signaling by wnt	158/4864	446/18723	5.08e-06	7.38e-05	158
GO:003424915	Skin	cSCC	negative regulation of cellular amide metabolic process	104/4864	273/18723	6.44e-06	9.00e-05	104
GO:005189324	Skin	cSCC	regulation of focal adhesion assembly	34/4864	66/18723	8.09e-06	1.09e-04	34
GO:009010924	Skin	cSCC	regulation of cell-substrate junction assembly	34/4864	66/18723	8.09e-06	1.09e-04	34
GO:200123822	Skin	cSCC	positive regulation of extrinsic apoptotic signaling pathway	27/4864	48/18723	8.24e-06	1.10e-04	27
GO:003297029	Skin	cSCC	regulation of actin filament-based process	142/4864	397/18723	8.50e-06	1.13e-04	142
GO:002260427	Skin	cSCC	regulation of cell morphogenesis	114/4864	309/18723	1.34e-05	1.68e-04	114
GO:003166825	Skin	cSCC	cellular response to extracellular stimulus	94/4864	246/18723	1.52e-05	1.87e-04	94
GO:004804124	Skin	cSCC	focal adhesion assembly	41/4864	87/18723	1.71e-05	2.07e-04	41
GO:003158926	Skin	cSCC	cell-substrate adhesion	130/4864	363/18723	1.87e-05	2.23e-04	130
GO:001714814	Skin	cSCC	negative regulation of translation	93/4864	245/18723	2.28e-05	2.63e-04	93

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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

DAP

SNV

Missense_Mutation

c.235G>C

p.Glu79Gln

p.E79Q

protein_coding

deleterious_low_confidence(0.02)

benign(0.015)

TCGA-E2-A1IN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

DAP

SNV

Missense_Mutation

rs753757154

c.278N>C

p.His93Pro

p.H93P

protein_coding

deleterious_low_confidence(0)

benign(0.01)

TCGA-E2-A1L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

DAP

SNV

Missense_Mutation

rs77265616

c.173G>A

p.Arg58Gln

p.R58Q

protein_coding

tolerated_low_confidence(0.08)

benign(0.029)

TCGA-5M-AAT4-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

DAP

SNV

Missense_Mutation

rs759102630

c.127N>A

p.Asp43Asn

p.D43N

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.984)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

DAP

SNV

Missense_Mutation

novel

c.167C>T

p.Ser56Phe

p.S56F

protein_coding

deleterious_low_confidence(0)

benign(0.036)

TCGA-NH-A5IV-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

DAP

SNV

Missense_Mutation

c.74G>A

p.Arg25Gln

p.R25Q

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.643)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

DAP

SNV

Missense_Mutation

novel

c.373C>A

p.Leu125Ile

p.L125I

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.534)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

DAP

SNV

Missense_Mutation

novel

c.391N>T

p.Leu131Phe

p.L131F

protein_coding

deleterious_low_confidence(0)

benign(0.003)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

DAP

SNV

Missense_Mutation

rs753757154

c.278N>C

p.His93Pro

p.H93P

protein_coding

deleterious_low_confidence(0)

benign(0.01)

TCGA-BG-A0VZ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

DAP

SNV

Missense_Mutation

rs370396587

c.182G>A

p.Arg61His

p.R61H

protein_coding

tolerated_low_confidence(0.16)

benign(0.009)

TCGA-D1-A17U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

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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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