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: AK2

Gene summary for AK2

Gene summary.

Gene information	Species	Human
	Gene symbol	AK2
	Gene ID	204
	Gene name	adenylate kinase 2
	Gene Alias	ADK2
	Cytomap	1p35.1
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	P54819

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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
204	AK2	HTA11_347_2000001011	Human	Colorectum	AD	7.50e-07	4.85e-01	-0.1954
204	AK2	HTA11_1391_2000001011	Human	Colorectum	AD	6.39e-05	5.86e-01	-0.059
204	AK2	HTA11_99999970781_79442	Human	Colorectum	MSS	2.39e-10	5.80e-01	0.294
204	AK2	HTA11_99999971662_82457	Human	Colorectum	MSS	2.17e-09	4.55e-01	0.3859
204	AK2	A015-C-203	Human	Colorectum	FAP	9.20e-05	-2.14e-01	-0.1294
204	AK2	A002-C-201	Human	Colorectum	FAP	1.90e-05	-1.93e-01	0.0324
204	AK2	A002-C-205	Human	Colorectum	FAP	2.28e-07	-1.84e-01	-0.1236
204	AK2	A015-C-006	Human	Colorectum	FAP	1.77e-03	-9.71e-02	-0.0994
204	AK2	A002-C-114	Human	Colorectum	FAP	3.03e-06	-2.20e-01	-0.1561
204	AK2	A015-C-104	Human	Colorectum	FAP	4.36e-05	-1.85e-01	-0.1899
204	AK2	A002-C-016	Human	Colorectum	FAP	1.14e-03	-1.38e-01	0.0521
204	AK2	A015-C-002	Human	Colorectum	FAP	2.52e-02	-1.47e-01	-0.0763
204	AK2	A002-C-116	Human	Colorectum	FAP	9.92e-08	-2.47e-01	-0.0452
204	AK2	A014-C-008	Human	Colorectum	FAP	1.36e-03	-1.39e-01	-0.191
204	AK2	A018-E-020	Human	Colorectum	FAP	4.08e-05	-1.61e-01	-0.2034
204	AK2	F034	Human	Colorectum	FAP	9.83e-03	-1.29e-01	-0.0665
204	AK2	CRC-1-8810	Human	Colorectum	CRC	4.92e-02	-1.40e-01	0.6257
204	AK2	LZE2T	Human	Esophagus	ESCC	9.59e-07	6.23e-01	0.082
204	AK2	LZE3D	Human	Esophagus	HGIN	2.77e-03	4.23e-01	0.0668
204	AK2	LZE4T	Human	Esophagus	ESCC	5.00e-19	5.13e-01	0.0811

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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
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:00066064	Colorectum	FAP	protein import into nucleus	38/2622	155/18723	3.23e-04	4.15e-03	38
GO:00092603	Colorectum	FAP	ribonucleotide biosynthetic process	43/2622	182/18723	3.23e-04	4.15e-03	43
GO:19012144	Colorectum	FAP	regulation of neuron death	67/2622	319/18723	3.73e-04	4.63e-03	67
GO:00170384	Colorectum	FAP	protein import	47/2622	206/18723	4.10e-04	4.94e-03	47
GO:00364734	Colorectum	FAP	cell death in response to oxidative stress	26/2622	95/18723	4.63e-04	5.39e-03	26
GO:00902763	Colorectum	FAP	regulation of peptide hormone secretion	45/2622	196/18723	4.66e-04	5.41e-03	45
GO:00900873	Colorectum	FAP	regulation of peptide transport	46/2622	202/18723	4.91e-04	5.66e-03	46
GO:00061643	Colorectum	FAP	purine nucleotide biosynthetic process	44/2622	191/18723	4.96e-04	5.71e-03	44
GO:00507142	Colorectum	FAP	positive regulation of protein secretion	34/2622	137/18723	5.11e-04	5.82e-03	34
GO:00068092	Colorectum	FAP	nitric oxide biosynthetic process	22/2622	76/18723	5.36e-04	6.06e-03	22
GO:00462092	Colorectum	FAP	nitric oxide metabolic process	23/2622	81/18723	5.48e-04	6.15e-03	23
GO:00603902	Colorectum	FAP	regulation of SMAD protein signal transduction	12/2622	31/18723	5.86e-04	6.51e-03	12
GO:20010572	Colorectum	FAP	reactive nitrogen species metabolic process	23/2622	82/18723	6.62e-04	7.21e-03	23
GO:19001824	Colorectum	FAP	positive regulation of protein localization to nucleus	24/2622	87/18723	6.65e-04	7.22e-03	24
GO:00458604	Colorectum	FAP	positive regulation of protein kinase activity	77/2622	386/18723	7.31e-04	7.81e-03	77
GO:00027913	Colorectum	FAP	regulation of peptide secretion	45/2622	200/18723	7.36e-04	7.83e-03	45
GO:00086314	Colorectum	FAP	intrinsic apoptotic signaling pathway in response to oxidative stress	15/2622	45/18723	8.14e-04	8.51e-03	15
GO:00463903	Colorectum	FAP	ribose phosphate biosynthetic process	43/2622	190/18723	8.40e-04	8.72e-03	43
GO:00300722	Colorectum	FAP	peptide hormone secretion	51/2622	236/18723	9.09e-04	9.19e-03	51
GO:19012153	Colorectum	FAP	negative regulation of neuron death	46/2622	208/18723	9.52e-04	9.42e-03	46

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa012325	Esophagus	ESCC	Nucleotide metabolism	59/4205	85/8465	1.67e-04	6.58e-04	3.37e-04	59
hsa012405	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa0123212	Esophagus	ESCC	Nucleotide metabolism	59/4205	85/8465	1.67e-04	6.58e-04	3.37e-04	59
hsa0124012	Esophagus	ESCC	Biosynthesis of cofactors	97/4205	153/8465	3.88e-04	1.35e-03	6.94e-04	97
hsa01240	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa01232	Liver	Cirrhotic	Nucleotide metabolism	39/2530	85/8465	1.27e-03	6.73e-03	4.15e-03	39
hsa012401	Liver	Cirrhotic	Biosynthesis of cofactors	66/2530	153/8465	3.11e-04	1.99e-03	1.23e-03	66
hsa012321	Liver	Cirrhotic	Nucleotide metabolism	39/2530	85/8465	1.27e-03	6.73e-03	4.15e-03	39
hsa012402	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa012322	Liver	HCC	Nucleotide metabolism	59/4020	85/8465	3.30e-05	1.88e-04	1.04e-04	59
hsa012403	Liver	HCC	Biosynthesis of cofactors	103/4020	153/8465	4.67e-07	5.05e-06	2.81e-06	103
hsa012323	Liver	HCC	Nucleotide metabolism	59/4020	85/8465	3.30e-05	1.88e-04	1.04e-04	59
hsa012324	Oral cavity	OSCC	Nucleotide metabolism	54/3704	85/8465	1.78e-04	5.95e-04	3.03e-04	54
hsa012404	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa0123211	Oral cavity	OSCC	Nucleotide metabolism	54/3704	85/8465	1.78e-04	5.95e-04	3.03e-04	54
hsa0124011	Oral cavity	OSCC	Biosynthesis of cofactors	88/3704	153/8465	3.84e-04	1.20e-03	6.12e-04	88
hsa0123221	Oral cavity	LP	Nucleotide metabolism	42/2418	85/8465	3.62e-05	2.36e-04	1.52e-04	42
hsa0124021	Oral cavity	LP	Biosynthesis of cofactors	57/2418	153/8465	1.17e-02	3.91e-02	2.52e-02	57
hsa0123231	Oral cavity	LP	Nucleotide metabolism	42/2418	85/8465	3.62e-05	2.36e-04	1.52e-04	42
hsa0124031	Oral cavity	LP	Biosynthesis of cofactors	57/2418	153/8465	1.17e-02	3.91e-02	2.52e-02	57

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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

AK2

insertion

In_Frame_Ins

novel

c.499-1_499insCCCATGAAAGATGAC

p.Pro162_Asp166dup

p.P162_D166dup

P54819

protein_coding

TCGA-AC-A3YI-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

AK2

insertion

Frame_Shift_Ins

novel

c.298_299insATAACACCTGCTTTGAGAA

p.Gly100AspfsTer20

p.G100Dfs*20

P54819

protein_coding

TCGA-BH-A0HQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

AK2

insertion

In_Frame_Ins

novel

c.499-1_499insCCCATGAAAGATGAC

p.Pro162_Asp166dup

p.P162_D166dup

P54819

protein_coding

TCGA-D8-A1JG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

AK2

SNV

Missense_Mutation

novel

c.98N>T

p.Pro33Leu

p.P33L

P54819

protein_coding

deleterious(0.01)

benign(0.074)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

AK2

SNV

Missense_Mutation

novel

c.353N>T

p.Arg118Met

p.R118M

P54819

protein_coding

deleterious(0.01)

probably_damaging(0.988)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

AK2

SNV

Missense_Mutation

rs770292274

c.368N>G

p.Asp123Gly

p.D123G

P54819

protein_coding

deleterious(0)

benign(0.399)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

AK2

SNV

Missense_Mutation

c.231N>C

p.Glu77Asp

p.E77D

P54819

protein_coding

tolerated(1)

benign(0.005)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

AK2

SNV

Missense_Mutation

rs370429097

c.610N>T

p.Arg204Trp

p.R204W

P54819

protein_coding

deleterious(0)

possibly_damaging(0.885)

TCGA-D1-A16G-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

taxol

AK2

SNV

Missense_Mutation

rs765991265

c.334G>A

p.Asp112Asn

p.D112N

P54819

protein_coding

deleterious(0.01)

possibly_damaging(0.844)

TCGA-EY-A1G8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

AK2

SNV

Missense_Mutation

c.524G>A

p.Arg175Gln

p.R175Q

P54819

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-BC-A10W-01

Liver

liver hepatocellular carcinoma

Male

<65

III/IV

Chemotherapy

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
204	AK2	ENZYME, KINASE		tenofovir	TENOFOVIR
204	AK2	ENZYME, KINASE		adefovir dipivoxil

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