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: ADAR

Gene summary for ADAR

Gene summary.

Gene information	Species	Human
	Gene symbol	ADAR
	Gene ID	103
	Gene name	adenosine deaminase RNA specific
	Gene Alias	ADAR1
	Cytomap	1q21.3
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	P55265

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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
103	ADAR	GSM4909281	Human	Breast	IDC	5.86e-14	4.18e-01	0.21
103	ADAR	GSM4909293	Human	Breast	IDC	1.97e-11	3.30e-01	0.1581
103	ADAR	GSM4909295	Human	Breast	IDC	2.57e-11	6.59e-01	0.0898
103	ADAR	GSM4909296	Human	Breast	IDC	4.17e-02	-7.43e-02	0.1524
103	ADAR	GSM4909298	Human	Breast	IDC	2.34e-08	3.00e-01	0.1551
103	ADAR	GSM4909302	Human	Breast	IDC	1.20e-05	4.17e-01	0.1545
103	ADAR	GSM4909307	Human	Breast	IDC	5.07e-21	5.77e-01	0.1569
103	ADAR	GSM4909308	Human	Breast	IDC	1.26e-19	5.76e-01	0.158
103	ADAR	GSM4909311	Human	Breast	IDC	1.31e-11	-3.54e-02	0.1534
103	ADAR	GSM4909312	Human	Breast	IDC	3.97e-04	7.94e-02	0.1552
103	ADAR	GSM4909317	Human	Breast	IDC	6.20e-09	4.51e-01	0.1355
103	ADAR	GSM4909319	Human	Breast	IDC	5.59e-15	-4.44e-02	0.1563
103	ADAR	GSM4909321	Human	Breast	IDC	9.65e-17	3.71e-01	0.1559
103	ADAR	M1	Human	Breast	IDC	8.43e-05	4.07e-01	0.1577
103	ADAR	M2	Human	Breast	IDC	6.51e-03	3.74e-01	0.21
103	ADAR	NCCBC14	Human	Breast	DCIS	1.19e-07	3.81e-01	0.2021
103	ADAR	NCCBC3	Human	Breast	DCIS	3.88e-05	1.99e-01	0.1198
103	ADAR	NCCBC5	Human	Breast	DCIS	5.12e-08	1.59e-01	0.2046
103	ADAR	P1	Human	Breast	IDC	2.74e-12	2.65e-01	0.1527
103	ADAR	DCIS2	Human	Breast	DCIS	9.49e-45	2.66e-01	0.0085

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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:00310541	Liver	HCC	pre-miRNA processing	13/7958	14/18723	1.25e-04	1.03e-03	13
GO:006096621	Liver	HCC	regulation of gene silencing by RNA	35/7958	53/18723	4.59e-04	3.04e-03	35
GO:006014721	Liver	HCC	regulation of posttranscriptional gene silencing	34/7958	52/18723	7.24e-04	4.42e-03	34
GO:0060338	Liver	HCC	regulation of type I interferon-mediated signaling pathway	24/7958	36/18723	2.95e-03	1.38e-02	24
GO:00450881	Liver	HCC	regulation of innate immune response	113/7958	218/18723	3.27e-03	1.50e-02	113
GO:00458241	Liver	HCC	negative regulation of innate immune response	42/7958	71/18723	3.41e-03	1.55e-02	42
GO:0050777	Liver	HCC	negative regulation of immune response	101/7958	194/18723	4.40e-03	1.90e-02	101
GO:0002200	Liver	HCC	somatic diversification of immune receptors	44/7958	77/18723	6.70e-03	2.72e-02	44
GO:000164911	Liver	HCC	osteoblast differentiation	115/7958	229/18723	1.08e-02	3.99e-02	115
GO:0016246	Liver	HCC	RNA interference	10/7958	13/18723	1.28e-02	4.61e-02	10
GO:002261320	Oral cavity	OSCC	ribonucleoprotein complex biogenesis	333/7305	463/18723	8.28e-48	5.24e-44	333
GO:001603220	Oral cavity	OSCC	viral process	274/7305	415/18723	2.42e-29	1.70e-26	274
GO:00344709	Oral cavity	OSCC	ncRNA processing	263/7305	395/18723	4.38e-29	2.78e-26	263
GO:00346605	Oral cavity	OSCC	ncRNA metabolic process	296/7305	485/18723	2.94e-23	6.65e-21	296
GO:001905820	Oral cavity	OSCC	viral life cycle	208/7305	317/18723	4.59e-22	1.00e-19	208
GO:007182620	Oral cavity	OSCC	ribonucleoprotein complex subunit organization	152/7305	227/18723	1.05e-17	1.01e-15	152
GO:002261820	Oral cavity	OSCC	ribonucleoprotein complex assembly	146/7305	220/18723	1.53e-16	1.23e-14	146
GO:001907920	Oral cavity	OSCC	viral genome replication	95/7305	131/18723	6.35e-15	4.02e-13	95
GO:000961515	Oral cavity	OSCC	response to virus	215/7305	367/18723	1.63e-14	9.41e-13	215
GO:005134820	Oral cavity	OSCC	negative regulation of transferase activity	165/7305	268/18723	5.02e-14	2.74e-12	165

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517144	Breast	DCIS	Coronavirus disease - COVID-19	86/846	232/8465	2.42e-29	1.56e-27	1.15e-27	86
hsa0517154	Breast	DCIS	Coronavirus disease - COVID-19	86/846	232/8465	2.42e-29	1.56e-27	1.15e-27	86
hsa05171	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa051711	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa051718	Colorectum	FAP	Coronavirus disease - COVID-19	78/1404	232/8465	9.94e-11	1.11e-08	6.73e-09	78
hsa051719	Colorectum	FAP	Coronavirus disease - COVID-19	78/1404	232/8465	9.94e-11	1.11e-08	6.73e-09	78
hsa0517139	Esophagus	HGIN	Coronavirus disease - COVID-19	105/1383	232/8465	7.84e-26	5.11e-24	4.06e-24	105
hsa0516420	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa05171115	Esophagus	HGIN	Coronavirus disease - COVID-19	105/1383	232/8465	7.84e-26	5.11e-24	4.06e-24	105
hsa05164110	Esophagus	HGIN	Influenza A	42/1383	171/8465	3.41e-03	2.54e-02	2.02e-02	42
hsa0516425	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0516435	Esophagus	ESCC	Influenza A	122/4205	171/8465	5.01e-09	4.79e-08	2.45e-08	122
hsa0517122	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa0516410	Liver	Cirrhotic	Influenza A	66/2530	171/8465	8.56e-03	2.91e-02	1.79e-02	66
hsa0517132	Liver	Cirrhotic	Coronavirus disease - COVID-19	136/2530	232/8465	3.28e-20	1.82e-18	1.12e-18	136
hsa0516411	Liver	Cirrhotic	Influenza A	66/2530	171/8465	8.56e-03	2.91e-02	1.79e-02	66
hsa0517142	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa0516421	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101
hsa0517152	Liver	HCC	Coronavirus disease - COVID-19	167/4020	232/8465	1.50e-14	4.19e-13	2.33e-13	167
hsa0516431	Liver	HCC	Influenza A	101/4020	171/8465	1.41e-03	5.07e-03	2.82e-03	101

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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

ADAR

SNV

Missense_Mutation

novel

c.2821N>C

p.Glu941Gln

p.E941Q

P55265

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

ADAR

SNV

Missense_Mutation

novel

c.32N>T

p.Gly11Val

p.G11V

P55265

protein_coding

tolerated_low_confidence(0.09)

benign(0.011)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

ADAR

SNV

Missense_Mutation

c.310N>T

p.Leu104Phe

p.L104F

P55265

protein_coding

tolerated(0.68)

benign(0.001)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

ADAR

SNV

Missense_Mutation

c.2893C>A

p.Pro965Thr

p.P965T

P55265

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADAR

SNV

Missense_Mutation

c.2693C>G

p.Ser898Cys

p.S898C

P55265

protein_coding

deleterious(0)

probably_damaging(0.956)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADAR

SNV

Missense_Mutation

novel

c.3477G>T

p.Lys1159Asn

p.K1159N

P55265

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ADAR

SNV

Missense_Mutation

c.3331N>C

p.Ile1111Leu

p.I1111L

P55265

protein_coding

deleterious(0)

benign(0.006)

TCGA-AR-A24R-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

ADAR

insertion

In_Frame_Ins

novel

c.2202_2203insTGTGGGCAGCTGCAACACACTGGTAAGTAT

p.Tyr734_Ala735insCysGlyGlnLeuGlnHisThrGlyLysTyr

p.Y734_A735insCGQLQHTGKY

P55265

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

ADAR

insertion

In_Frame_Ins

novel

c.480_481insGCCCTCCTT

p.Asp160_Leu161insAlaLeuLeu

p.D160_L161insALL

P55265

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

ADAR

insertion

Frame_Shift_Ins

novel

c.2972_2973insGGGTAAGGAGACAGGAGAGCGCAGTGAGGACCAAGCCTCTG

p.Phe992GlyfsTer76

p.F992Gfs*76

P55265

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

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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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