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: AKT1

Gene summary for AKT1

Gene summary.

Gene information	Species	Human
	Gene symbol	AKT1
	Gene ID	207
	Gene name	AKT serine/threonine kinase 1
	Gene Alias	AKT
	Cytomap	14q32.33
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	B0LPE5

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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
207	AKT1	HTA11_2487_2000001011	Human	Colorectum	SER	3.82e-07	4.27e-01	-0.1808
207	AKT1	HTA11_1938_2000001011	Human	Colorectum	AD	1.27e-07	4.56e-01	-0.0811
207	AKT1	HTA11_78_2000001011	Human	Colorectum	AD	4.14e-04	3.04e-01	-0.1088
207	AKT1	HTA11_347_2000001011	Human	Colorectum	AD	6.28e-14	4.37e-01	-0.1954
207	AKT1	HTA11_411_2000001011	Human	Colorectum	SER	5.15e-03	5.54e-01	-0.2602
207	AKT1	HTA11_83_2000001011	Human	Colorectum	SER	2.63e-03	3.35e-01	-0.1526
207	AKT1	HTA11_696_2000001011	Human	Colorectum	AD	1.25e-14	4.50e-01	-0.1464
207	AKT1	HTA11_866_2000001011	Human	Colorectum	AD	2.37e-03	2.38e-01	-0.1001
207	AKT1	HTA11_1391_2000001011	Human	Colorectum	AD	4.26e-10	4.42e-01	-0.059
207	AKT1	HTA11_2992_2000001011	Human	Colorectum	SER	1.68e-02	4.39e-01	-0.1706
207	AKT1	HTA11_546_2000001011	Human	Colorectum	AD	7.46e-04	3.74e-01	-0.0842
207	AKT1	HTA11_866_3004761011	Human	Colorectum	AD	1.70e-06	2.33e-01	0.096
207	AKT1	HTA11_10623_2000001011	Human	Colorectum	AD	3.02e-03	3.30e-01	-0.0177
207	AKT1	HTA11_7696_3000711011	Human	Colorectum	AD	1.20e-09	2.89e-01	0.0674
207	AKT1	HTA11_7469_2000001011	Human	Colorectum	AD	6.88e-03	4.96e-01	-0.0124
207	AKT1	HTA11_99999970781_79442	Human	Colorectum	MSS	7.38e-06	3.07e-01	0.294
207	AKT1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.19e-02	7.01e-01	0.3487
207	AKT1	HTA11_99999965104_69814	Human	Colorectum	MSS	3.57e-09	4.13e-01	0.281
207	AKT1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.03e-04	2.43e-01	0.3859
207	AKT1	HTA11_99999973899_84307	Human	Colorectum	MSS	2.32e-03	4.00e-01	0.2585

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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
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:0070227	Oral cavity	OSCC	lymphocyte apoptotic process	40/7305	72/18723	3.21e-03	1.38e-02	40
GO:00620128	Oral cavity	OSCC	regulation of small molecule metabolic process	155/7305	334/18723	3.30e-03	1.41e-02	155
GO:00457371	Oral cavity	OSCC	positive regulation of cyclin-dependent protein serine/threonine kinase activity	19/7305	29/18723	3.47e-03	1.47e-02	19
GO:00181079	Oral cavity	OSCC	peptidyl-threonine phosphorylation	60/7305	116/18723	3.59e-03	1.50e-02	60
GO:19040311	Oral cavity	OSCC	positive regulation of cyclin-dependent protein kinase activity	21/7305	33/18723	3.63e-03	1.51e-02	21
GO:00182109	Oral cavity	OSCC	peptidyl-threonine modification	64/7305	125/18723	3.68e-03	1.52e-02	64
GO:005087010	Oral cavity	OSCC	positive regulation of T cell activation	104/7305	216/18723	3.76e-03	1.55e-02	104
GO:003087910	Oral cavity	OSCC	mammary gland development	69/7305	137/18723	4.43e-03	1.79e-02	69
GO:00331354	Oral cavity	OSCC	regulation of peptidyl-serine phosphorylation	72/7305	144/18723	4.66e-03	1.87e-02	72
GO:00426927	Oral cavity	OSCC	muscle cell differentiation	175/7305	384/18723	4.79e-03	1.92e-02	175
GO:001063218	Oral cavity	OSCC	regulation of epithelial cell migration	136/7305	292/18723	4.82e-03	1.92e-02	136
GO:00068514	Oral cavity	OSCC	mitochondrial calcium ion transmembrane transport	14/7305	20/18723	4.95e-03	1.94e-02	14
GO:00486614	Oral cavity	OSCC	positive regulation of smooth muscle cell proliferation	54/7305	104/18723	5.00e-03	1.96e-02	54
GO:00447067	Oral cavity	OSCC	multi-multicellular organism process	105/7305	220/18723	5.05e-03	1.97e-02	105
GO:00160513	Oral cavity	OSCC	carbohydrate biosynthetic process	97/7305	202/18723	5.50e-03	2.13e-02	97
GO:190040718	Oral cavity	OSCC	regulation of cellular response to oxidative stress	47/7305	89/18723	5.62e-03	2.17e-02	47
GO:000680915	Oral cavity	OSCC	nitric oxide biosynthetic process	41/7305	76/18723	5.78e-03	2.22e-02	41
GO:20004013	Oral cavity	OSCC	regulation of lymphocyte migration	34/7305	61/18723	5.90e-03	2.25e-02	34
GO:00486596	Oral cavity	OSCC	smooth muscle cell proliferation	89/7305	184/18723	5.95e-03	2.27e-02	89
GO:00714022	Oral cavity	OSCC	cellular response to lipoprotein particle stimulus	22/7305	36/18723	5.96e-03	2.27e-02	22

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05208	Colorectum	AD	Chemical carcinogenesis - reactive oxygen species	126/2092	223/8465	1.01e-24	1.68e-22	1.07e-22	126
hsa05415	Colorectum	AD	Diabetic cardiomyopathy	114/2092	203/8465	3.65e-22	3.06e-20	1.95e-20	114
hsa05010	Colorectum	AD	Alzheimer disease	174/2092	384/8465	1.82e-19	9.26e-18	5.91e-18	174
hsa04932	Colorectum	AD	Non-alcoholic fatty liver disease	90/2092	155/8465	4.83e-19	1.80e-17	1.15e-17	90
hsa05131	Colorectum	AD	Shigellosis	109/2092	247/8465	1.09e-11	2.44e-10	1.55e-10	109
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa04666	Colorectum	AD	Fc gamma R-mediated phagocytosis	46/2092	97/8465	9.10e-07	1.22e-05	7.77e-06	46
hsa05017	Colorectum	AD	Spinocerebellar ataxia	60/2092	143/8465	3.78e-06	4.35e-05	2.78e-05	60
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa04066	Colorectum	AD	HIF-1 signaling pathway	48/2092	109/8465	7.25e-06	7.84e-05	5.00e-05	48
hsa04919	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa04722	Colorectum	AD	Neurotrophin signaling pathway	50/2092	119/8465	2.28e-05	2.24e-04	1.43e-04	50
hsa05213	Colorectum	AD	Endometrial cancer	29/2092	58/8465	2.69e-05	2.57e-04	1.64e-04	29
hsa05230	Colorectum	AD	Central carbon metabolism in cancer	33/2092	70/8465	3.61e-05	3.19e-04	2.03e-04	33
hsa05418	Colorectum	AD	Fluid shear stress and atherosclerosis	54/2092	139/8465	1.41e-04	1.16e-03	7.37e-04	54
hsa04152	Colorectum	AD	AMPK signaling pathway	47/2092	121/8465	3.74e-04	2.82e-03	1.80e-03	47
hsa05210	Colorectum	AD	Colorectal cancer	35/2092	86/8465	7.54e-04	5.49e-03	3.50e-03	35
hsa04213	Colorectum	AD	Longevity regulating pathway - multiple species	27/2092	62/8465	8.72e-04	5.96e-03	3.80e-03	27
hsa04922	Colorectum	AD	Glucagon signaling pathway	41/2092	107/8465	1.18e-03	7.75e-03	4.94e-03	41
hsa05417	Colorectum	AD	Lipid and atherosclerosis	73/2092	215/8465	1.31e-03	8.27e-03	5.27e-03	73

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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

AKT1

SNV

Missense_Mutation

novel

c.618N>T

p.Arg206Ser

p.R206S

P31749

protein_coding

tolerated(0.32)

benign(0.023)

TCGA-A7-A13G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

AKT1

SNV

Missense_Mutation

rs121434592

c.49G>A

p.Glu17Lys

p.E17K

P31749

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AKT1

SNV

Missense_Mutation

rs121434592

c.49G>A

p.Glu17Lys

p.E17K

P31749

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A6IX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

AKT1

SNV

Missense_Mutation

c.155N>G

p.Leu52Arg

p.L52R

P31749

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AN-A0XR-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

AKT1

SNV

Missense_Mutation

rs121434592

c.49G>A

p.Glu17Lys

p.E17K

P31749

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AO-A12H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

AKT1

SNV

Missense_Mutation

rs121434592

c.49G>A

p.Glu17Lys

p.E17K

P31749

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A24X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

AKT1

SNV

Missense_Mutation

rs121434592

c.49G>A

p.Glu17Lys

p.E17K

P31749

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B6-A0WZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AKT1

SNV

Missense_Mutation

rs121434592

c.49N>A

p.Glu17Lys

p.E17K

P31749

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0BR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AKT1

SNV

Missense_Mutation

rs121434592

c.49N>A

p.Glu17Lys

p.E17K

P31749

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0BS-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

AKT1

SNV

Missense_Mutation

rs121434592

c.49N>A

p.Glu17Lys

p.E17K

P31749

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0W4-01

Breast

breast invasive carcinoma

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
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE	inhibitor	178101884	GSK-690693
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE		AZD4547		26351323
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE		PTX-200
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE	inhibitor	CHEMBL3137336	UPROSERTIB
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE	inhibitor	249565578	IPATASERTIB
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE		Ipatasertib	IPATASERTIB	27872130
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE		GAMBOGIC AMIDE	GAMBOGIC AMIDE	17911251
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE		GDC-0068	IPATASERTIB
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE		SOTRASTAURIN	SOTRASTAURIN
207	AKT1	SERINE THREONINE KINASE, KINASE, ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, TRANSPORTER, TRANSCRIPTION FACTOR, DRUG RESISTANCE	inhibitor	MK-2206	MK-2206

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