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: CALM3

Gene summary for CALM3

Gene summary.

Gene information	Species	Human
	Gene symbol	CALM3
	Gene ID	808
	Gene name	calmodulin 3
	Gene Alias	CALM
	Cytomap	19q13.32
	Gene Type	protein-coding
	GO ID	GO:0000086
	UniProtAcc	Q96HY3

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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
808	CALM3	GSM4909281	Human	Breast	IDC	8.47e-08	3.90e-01	0.21
808	CALM3	GSM4909288	Human	Breast	IDC	6.95e-03	2.01e-01	0.0988
808	CALM3	GSM4909291	Human	Breast	IDC	8.07e-48	1.08e+00	0.1753
808	CALM3	GSM4909296	Human	Breast	IDC	3.19e-03	-4.61e-02	0.1524
808	CALM3	GSM4909298	Human	Breast	IDC	9.37e-09	3.49e-01	0.1551
808	CALM3	GSM4909301	Human	Breast	IDC	1.75e-25	6.45e-01	0.1577
808	CALM3	GSM4909304	Human	Breast	IDC	3.46e-08	3.06e-01	0.1636
808	CALM3	GSM4909306	Human	Breast	IDC	5.51e-04	3.01e-01	0.1564
808	CALM3	GSM4909307	Human	Breast	IDC	1.56e-07	3.71e-01	0.1569
808	CALM3	GSM4909308	Human	Breast	IDC	8.96e-24	6.40e-01	0.158
808	CALM3	GSM4909311	Human	Breast	IDC	5.87e-17	7.58e-02	0.1534
808	CALM3	GSM4909312	Human	Breast	IDC	6.67e-10	3.05e-01	0.1552
808	CALM3	GSM4909316	Human	Breast	IDC	2.28e-04	3.90e-01	0.21
808	CALM3	GSM4909318	Human	Breast	IDC	1.39e-02	3.86e-01	0.2031
808	CALM3	GSM4909319	Human	Breast	IDC	1.64e-17	-1.68e-01	0.1563
808	CALM3	GSM4909320	Human	Breast	IDC	3.95e-02	2.03e-01	0.1575
808	CALM3	GSM4909321	Human	Breast	IDC	4.98e-10	2.48e-01	0.1559
808	CALM3	brca2	Human	Breast	Precancer	9.20e-04	2.39e-01	-0.024
808	CALM3	M1	Human	Breast	IDC	1.41e-05	4.48e-01	0.1577
808	CALM3	NCCBC14	Human	Breast	DCIS	5.74e-08	2.32e-01	0.2021

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:0034766	Endometrium	AEH	negative regulation of ion transmembrane transport	22/2100	109/18723	4.39e-03	2.89e-02	22
GO:00603155	Endometrium	AEH	negative regulation of ryanodine-sensitive calcium-release channel activity	5/2100	11/18723	4.56e-03	2.95e-02	5
GO:00105232	Endometrium	AEH	negative regulation of calcium ion transport into cytosol	7/2100	20/18723	4.57e-03	2.95e-02	7
GO:00613375	Endometrium	AEH	cardiac conduction	20/2100	98/18723	5.64e-03	3.46e-02	20
GO:0043271	Endometrium	AEH	negative regulation of ion transport	29/2100	160/18723	6.16e-03	3.70e-02	29
GO:00228986	Endometrium	AEH	regulation of transmembrane transporter activity	45/2100	278/18723	7.34e-03	4.18e-02	45
GO:00484884	Endometrium	AEH	synaptic vesicle endocytosis	14/2100	62/18723	7.72e-03	4.33e-02	14
GO:01402384	Endometrium	AEH	presynaptic endocytosis	14/2100	62/18723	7.72e-03	4.33e-02	14
GO:00108821	Endometrium	AEH	regulation of cardiac muscle contraction by calcium ion signaling	8/2100	27/18723	7.74e-03	4.33e-02	8
GO:0034763	Endometrium	AEH	negative regulation of transmembrane transport	26/2100	143/18723	8.78e-03	4.78e-02	26
GO:1904063	Endometrium	AEH	negative regulation of cation transmembrane transport	20/2100	102/18723	8.88e-03	4.82e-02	20
GO:19040623	Endometrium	AEH	regulation of cation transmembrane transport	55/2100	357/18723	9.18e-03	4.96e-02	55
GO:007259415	Endometrium	EEC	establishment of protein localization to organelle	94/2168	422/18723	2.22e-10	2.51e-08	94
GO:005109817	Endometrium	EEC	regulation of binding	83/2168	363/18723	6.72e-10	6.61e-08	83
GO:004854517	Endometrium	EEC	response to steroid hormone	77/2168	339/18723	3.80e-09	2.71e-07	77
GO:005109917	Endometrium	EEC	positive regulation of binding	44/2168	173/18723	3.08e-07	1.27e-05	44
GO:190165416	Endometrium	EEC	response to ketone	46/2168	194/18723	1.44e-06	4.64e-05	46
GO:007058515	Endometrium	EEC	protein localization to mitochondrion	33/2168	125/18723	3.74e-06	1.00e-04	33
GO:007265515	Endometrium	EEC	establishment of protein localization to mitochondrion	32/2168	120/18723	4.14e-06	1.07e-04	32
GO:005110117	Endometrium	EEC	regulation of DNA binding	31/2168	118/18723	8.11e-06	1.81e-04	31

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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
hsa0497114	Breast	Precancer	Gastric acid secretion	13/684	76/8465	7.35e-03	4.07e-02	3.12e-02	13
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

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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

CALM3

SNV

Missense_Mutation

novel

c.214N>T

p.Met72Leu

p.M72L

P62158

protein_coding

tolerated_low_confidence(0.66)

benign(0.015)

TCGA-C5-A8YQ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

CALM3

SNV

Missense_Mutation

c.27N>C

p.Gln9His

p.Q9H

P62158

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.625)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

CALM3

SNV

Missense_Mutation

novel

c.150N>T

p.Gln50His

p.Q50H

P62158

protein_coding

deleterious_low_confidence(0.05)

benign(0.054)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

CALM3

SNV

Missense_Mutation

novel

c.150G>T

p.Gln50His

p.Q50H

P62158

protein_coding

deleterious_low_confidence(0.05)

benign(0.054)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CALM3

SNV

Missense_Mutation

novel

c.31G>A

p.Ala11Thr

p.A11T

P62158

protein_coding

deleterious_low_confidence(0.02)

benign(0.009)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

CALM3

SNV

Missense_Mutation

novel

c.265G>A

p.Ala89Thr

p.A89T

P62158

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.774)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

CALM3

SNV

Missense_Mutation

novel

c.107T>C

p.Val36Ala

p.V36A

P62158

protein_coding

deleterious_low_confidence(0.03)

possibly_damaging(0.842)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CALM3

SNV

Missense_Mutation

novel

c.319C>T

p.Arg107Cys

p.R107C

P62158

protein_coding

tolerated_low_confidence(0.07)

benign(0.015)

TCGA-EY-A215-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CALM3

SNV

Missense_Mutation

novel

c.35A>G

p.Glu12Gly

p.E12G

P62158

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.981)

TCGA-FI-A2F4-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CALM3

SNV

Missense_Mutation

novel

c.178G>C

p.Gly60Arg

p.G60R

P62158

protein_coding

deleterious_low_confidence(0.05)

possibly_damaging(0.654)

TCGA-37-A5EL-01

Lung

lung squamous cell carcinoma

Male

<65

I/II

Chemotherapy

temodal

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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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