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: DDB1

Gene summary for DDB1

Gene summary.

Gene information	Species	Human
	Gene symbol	DDB1
	Gene ID	1642
	Gene name	damage specific DNA binding protein 1
	Gene Alias	DDBA
	Cytomap	11q12.2
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	Q16531

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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
1642	DDB1	HTA11_2487_2000001011	Human	Colorectum	SER	1.78e-02	4.48e-01	-0.1808
1642	DDB1	HTA11_1938_2000001011	Human	Colorectum	AD	1.49e-08	5.70e-01	-0.0811
1642	DDB1	HTA11_78_2000001011	Human	Colorectum	AD	2.34e-04	4.36e-01	-0.1088
1642	DDB1	HTA11_347_2000001011	Human	Colorectum	AD	9.67e-18	6.09e-01	-0.1954
1642	DDB1	HTA11_411_2000001011	Human	Colorectum	SER	1.13e-03	6.05e-01	-0.2602
1642	DDB1	HTA11_83_2000001011	Human	Colorectum	SER	3.40e-06	4.81e-01	-0.1526
1642	DDB1	HTA11_696_2000001011	Human	Colorectum	AD	3.19e-06	4.33e-01	-0.1464
1642	DDB1	HTA11_1391_2000001011	Human	Colorectum	AD	1.35e-11	6.83e-01	-0.059
1642	DDB1	HTA11_2992_2000001011	Human	Colorectum	SER	2.57e-03	5.97e-01	-0.1706
1642	DDB1	HTA11_866_3004761011	Human	Colorectum	AD	3.33e-11	5.97e-01	0.096
1642	DDB1	HTA11_4255_2000001011	Human	Colorectum	SER	5.40e-04	5.94e-01	0.0446
1642	DDB1	HTA11_6801_2000001011	Human	Colorectum	SER	9.38e-03	6.64e-01	0.0171
1642	DDB1	HTA11_7696_3000711011	Human	Colorectum	AD	3.60e-03	4.04e-01	0.0674
1642	DDB1	HTA11_6818_2000001021	Human	Colorectum	AD	8.52e-03	3.84e-01	0.0588
1642	DDB1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.67e-12	5.74e-01	0.294
1642	DDB1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	7.65e-04	9.94e-01	0.3487
1642	DDB1	HTA11_99999965104_69814	Human	Colorectum	MSS	1.71e-07	5.88e-01	0.281
1642	DDB1	HTA11_99999971662_82457	Human	Colorectum	MSS	8.05e-11	8.30e-01	0.3859
1642	DDB1	A015-C-203	Human	Colorectum	FAP	2.68e-07	-1.81e-01	-0.1294
1642	DDB1	A001-C-108	Human	Colorectum	FAP	3.82e-05	-1.41e-01	-0.0272

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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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
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:0016032	Colorectum	AD	viral process	168/3918	415/18723	4.67e-20	3.66e-17	168
GO:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0019058	Colorectum	AD	viral life cycle	119/3918	317/18723	6.18e-12	8.23e-10	119
GO:0045732	Colorectum	AD	positive regulation of protein catabolic process	92/3918	231/18723	3.85e-11	4.47e-09	92
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0044403	Colorectum	AD	biological process involved in symbiotic interaction	99/3918	290/18723	1.02e-07	4.93e-06	99
GO:0051701	Colorectum	AD	biological process involved in interaction with host	73/3918	203/18723	5.08e-07	1.88e-05	73
GO:0048524	Colorectum	AD	positive regulation of viral process	31/3918	65/18723	1.33e-06	4.23e-05	31
GO:0019079	Colorectum	AD	viral genome replication	51/3918	131/18723	1.83e-06	5.51e-05	51
GO:0052126	Colorectum	AD	movement in host environment	63/3918	175/18723	2.85e-06	8.11e-05	63
GO:0007623	Colorectum	AD	circadian rhythm	72/3918	210/18723	4.50e-06	1.21e-04	72
GO:0050792	Colorectum	AD	regulation of viral process	59/3918	164/18723	5.95e-06	1.52e-04	59
GO:0048511	Colorectum	AD	rhythmic process	94/3918	298/18723	1.00e-05	2.34e-04	94
GO:0016055	Colorectum	AD	Wnt signaling pathway	130/3918	444/18723	1.60e-05	3.37e-04	130
GO:0019318	Colorectum	AD	hexose metabolic process	77/3918	237/18723	1.96e-05	4.01e-04	77
GO:0198738	Colorectum	AD	cell-cell signaling by wnt	130/3918	446/18723	2.02e-05	4.10e-04	130
GO:0044262	Colorectum	AD	cellular carbohydrate metabolic process	87/3918	283/18723	6.00e-05	1.01e-03	87
GO:0005996	Colorectum	AD	monosaccharide metabolic process	80/3918	257/18723	7.31e-05	1.17e-03	80

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa051701	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051702	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa051703	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa051704	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa05161	Colorectum	MSS	Hepatitis B	48/1875	162/8465	1.53e-02	4.93e-02	3.02e-02	48
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa051705	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa051611	Colorectum	MSS	Hepatitis B	48/1875	162/8465	1.53e-02	4.93e-02	3.02e-02	48
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa051706	Colorectum	FAP	Human immunodeficiency virus 1 infection	51/1404	212/8465	2.98e-03	1.29e-02	7.87e-03	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa051707	Colorectum	FAP	Human immunodeficiency virus 1 infection	51/1404	212/8465	2.98e-03	1.29e-02	7.87e-03	51
hsa034205	Esophagus	HGIN	Nucleotide excision repair	29/1383	63/8465	2.96e-08	5.36e-07	4.26e-07	29
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49

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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

DDB1

SNV

Missense_Mutation

c.1723G>A

p.Glu575Lys

p.E575K

Q16531

protein_coding

tolerated(0.24)

benign(0.005)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DDB1

SNV

Missense_Mutation

novel

c.3205N>A

p.Glu1069Lys

p.E1069K

Q16531

protein_coding

tolerated(0.31)

benign(0.005)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DDB1

SNV

Missense_Mutation

c.148N>T

p.Arg50Trp

p.R50W

Q16531

protein_coding

deleterious(0.01)

possibly_damaging(0.901)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDB1

SNV

Missense_Mutation

novel

c.1623N>T

p.Leu541Phe

p.L541F

Q16531

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-AR-A1AP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

DDB1

SNV

Missense_Mutation

c.725G>A

p.Gly242Asp

p.G242D

Q16531

protein_coding

deleterious(0)

possibly_damaging(0.904)

TCGA-B6-A0RO-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

DDB1

SNV

Missense_Mutation

c.1963N>T

p.Arg655Cys

p.R655C

Q16531

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DDB1

SNV

Missense_Mutation

c.2722A>C

p.Asn908His

p.N908H

Q16531

protein_coding

tolerated(0.62)

benign(0.047)

TCGA-E9-A22G-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

DDB1

insertion

Frame_Shift_Ins

rs757472327

c.685_686insG

p.Ala229GlyfsTer15

p.A229Gfs*15

Q16531

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDB1

insertion

Frame_Shift_Ins

rs757472327

c.685_686insG

p.Ala229GlyfsTer15

p.A229Gfs*15

Q16531

protein_coding

TCGA-AN-A0FY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DDB1

insertion

Frame_Shift_Ins

rs757472327

c.685dupG

p.Ala229GlyfsTer15

p.A229Gfs*15

Q16531

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

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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
1642	DDB1	DNA REPAIR	inhibitor	CHEMBL468	THALIDOMIDE
1642	DDB1	DNA REPAIR	inhibitor	CHEMBL43452	POMALIDOMIDE
1642	DDB1	DNA REPAIR	inhibitor	CHEMBL848	LENALIDOMIDE

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