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: CALM2

Gene summary for CALM2

Gene summary.

Gene information	Species	Human
	Gene symbol	CALM2
	Gene ID	805
	Gene name	calmodulin 2
	Gene Alias	CALM
	Cytomap	2p21
	Gene Type	protein-coding
	GO ID	GO:0000086
	UniProtAcc	P0DP24

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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
805	CALM2	GSM4909280	Human	Breast	Precancer	6.13e-03	-3.26e-01	0.0305
805	CALM2	GSM4909281	Human	Breast	IDC	3.92e-18	3.00e-01	0.21
805	CALM2	GSM4909282	Human	Breast	IDC	1.08e-44	4.19e-01	-0.0288
805	CALM2	GSM4909285	Human	Breast	IDC	9.60e-17	2.62e-01	0.21
805	CALM2	GSM4909286	Human	Breast	IDC	1.20e-06	1.84e-01	0.1081
805	CALM2	GSM4909287	Human	Breast	IDC	6.54e-04	-3.78e-02	0.2057
805	CALM2	GSM4909289	Human	Breast	IDC	4.04e-06	3.49e-01	0.1064
805	CALM2	GSM4909290	Human	Breast	IDC	5.06e-06	2.27e-01	0.2096
805	CALM2	GSM4909293	Human	Breast	IDC	3.80e-04	-9.64e-02	0.1581
805	CALM2	GSM4909294	Human	Breast	IDC	1.31e-13	5.99e-02	0.2022
805	CALM2	GSM4909295	Human	Breast	IDC	2.05e-02	2.20e-01	0.0898
805	CALM2	GSM4909296	Human	Breast	IDC	2.10e-10	5.27e-02	0.1524
805	CALM2	GSM4909297	Human	Breast	IDC	5.26e-23	3.53e-02	0.1517
805	CALM2	GSM4909299	Human	Breast	IDC	2.26e-15	2.74e-01	0.035
805	CALM2	GSM4909300	Human	Breast	IDC	5.48e-04	2.56e-01	0.0334
805	CALM2	GSM4909302	Human	Breast	IDC	9.25e-04	-2.71e-01	0.1545
805	CALM2	GSM4909305	Human	Breast	IDC	2.75e-11	2.93e-01	0.0436
805	CALM2	GSM4909306	Human	Breast	IDC	1.72e-05	1.99e-01	0.1564
805	CALM2	GSM4909307	Human	Breast	IDC	6.15e-21	3.20e-01	0.1569
805	CALM2	GSM4909308	Human	Breast	IDC	8.79e-33	3.99e-01	0.158

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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:001810715	Oral cavity	EOLP	peptidyl-threonine phosphorylation	33/2218	116/18723	1.02e-06	2.51e-05	33
GO:005109924	Oral cavity	EOLP	positive regulation of binding	42/2218	173/18723	3.81e-06	8.06e-05	42
GO:004477222	Oral cavity	EOLP	mitotic cell cycle phase transition	81/2218	424/18723	8.32e-06	1.59e-04	81
GO:001092114	Oral cavity	EOLP	regulation of phosphatase activity	25/2218	84/18723	8.43e-06	1.61e-04	25
GO:004586017	Oral cavity	EOLP	positive regulation of protein kinase activity	74/2218	386/18723	1.78e-05	2.89e-04	74
GO:004677713	Oral cavity	EOLP	protein autophosphorylation	49/2218	227/18723	2.04e-05	3.21e-04	49
GO:003530712	Oral cavity	EOLP	positive regulation of protein dephosphorylation	16/2218	45/18723	3.15e-05	4.46e-04	16
GO:001003826	Oral cavity	EOLP	response to metal ion	71/2218	373/18723	3.32e-05	4.65e-04	71
GO:00325164	Oral cavity	EOLP	positive regulation of phosphoprotein phosphatase activity	10/2218	21/18723	5.45e-05	7.01e-04	10
GO:003530612	Oral cavity	EOLP	positive regulation of dephosphorylation	18/2218	59/18723	1.05e-04	1.19e-03	18
GO:003367419	Oral cavity	EOLP	positive regulation of kinase activity	82/2218	467/18723	1.58e-04	1.68e-03	82
GO:00515929	Oral cavity	EOLP	response to calcium ion	33/2218	149/18723	2.62e-04	2.54e-03	33
GO:002176224	Oral cavity	EOLP	substantia nigra development	14/2218	44/18723	3.72e-04	3.38e-03	14
GO:00510517	Oral cavity	EOLP	negative regulation of transport	80/2218	470/18723	5.11e-04	4.44e-03	80
GO:007190214	Oral cavity	EOLP	positive regulation of protein serine/threonine kinase activity	40/2218	200/18723	5.93e-04	4.99e-03	40
GO:005110124	Oral cavity	EOLP	regulation of DNA binding	26/2218	118/18723	1.21e-03	8.75e-03	26
GO:00109225	Oral cavity	EOLP	positive regulation of phosphatase activity	11/2218	34/18723	1.34e-03	9.33e-03	11
GO:004338817	Oral cavity	EOLP	positive regulation of DNA binding	15/2218	56/18723	1.73e-03	1.14e-02	15
GO:003090123	Oral cavity	EOLP	midbrain development	20/2218	90/18723	3.81e-03	2.11e-02	20
GO:004885717	Oral cavity	EOLP	neural nucleus development	15/2218	64/18723	6.83e-03	3.32e-02	15

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501218	Breast	Precancer	Parkinson disease	99/684	266/8465	3.58e-42	5.65e-40	4.33e-40	99
hsa0501016	Breast	Precancer	Alzheimer disease	103/684	384/8465	1.03e-29	4.66e-28	3.57e-28	103
hsa0502216	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0516718	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0491518	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0541818	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa0541718	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa042189	Breast	Precancer	Cellular senescence	29/684	156/8465	1.66e-05	1.69e-04	1.30e-04	29
hsa05031	Breast	Precancer	Amphetamine addiction	14/684	69/8465	1.05e-03	7.35e-03	5.63e-03	14
hsa0516316	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32
hsa0501219	Breast	Precancer	Parkinson disease	99/684	266/8465	3.58e-42	5.65e-40	4.33e-40	99
hsa0501017	Breast	Precancer	Alzheimer disease	103/684	384/8465	1.03e-29	4.66e-28	3.57e-28	103
hsa0502217	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0516719	Breast	Precancer	Kaposi sarcoma-associated herpesvirus infection	36/684	194/8465	1.68e-06	2.53e-05	1.94e-05	36
hsa0491519	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0541819	Breast	Precancer	Fluid shear stress and atherosclerosis	28/684	139/8465	4.74e-06	6.00e-05	4.59e-05	28
hsa0541719	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0421814	Breast	Precancer	Cellular senescence	29/684	156/8465	1.66e-05	1.69e-04	1.30e-04	29
hsa050311	Breast	Precancer	Amphetamine addiction	14/684	69/8465	1.05e-03	7.35e-03	5.63e-03	14
hsa0516317	Breast	Precancer	Human cytomegalovirus infection	32/684	225/8465	1.13e-03	7.57e-03	5.80e-03	32

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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

CALM2

SNV

Missense_Mutation

c.39C>G

p.Phe13Leu

p.F13L

P62158

protein_coding

deleterious_low_confidence(0.03)

benign(0.206)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CALM2

SNV

Missense_Mutation

c.193G>C

p.Asp65His

p.D65H

P62158

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.845)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CALM2

SNV

Missense_Mutation

c.319N>T

p.Arg107Cys

p.R107C

P62158

protein_coding

tolerated_low_confidence(0.07)

benign(0.015)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

CALM2

SNV

Missense_Mutation

c.77N>A

p.Gly26Glu

p.G26E

P62158

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.903)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CALM2

SNV

Missense_Mutation

novel

c.334A>G

p.Asn112Asp

p.N112D

P62158

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.623)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CALM2

SNV

Missense_Mutation

c.319N>T

p.Arg107Cys

p.R107C

P62158

protein_coding

tolerated_low_confidence(0.07)

benign(0.015)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

CALM2

SNV

Missense_Mutation

c.185G>A

p.Gly62Asp

p.G62D

P62158

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.89)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CALM2

SNV

Missense_Mutation

c.343N>A

p.Glu115Lys

p.E115K

P62158

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.851)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

CALM2

SNV

Missense_Mutation

novel

c.345N>T

p.Glu115Asp

p.E115D

P62158

protein_coding

deleterious_low_confidence(0.02)

benign(0.337)

TCGA-B5-A11N-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CALM2

SNV

Missense_Mutation

c.185N>A

p.Gly62Asp

p.G62D

P62158

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.89)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid 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

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