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: CALML3

Gene summary for CALML3

Gene summary.

Gene information	Species	Human
	Gene symbol	CALML3
	Gene ID	810
	Gene name	calmodulin like 3
	Gene Alias	CLP
	Cytomap	10p15.1
	Gene Type	protein-coding
	GO ID	GO:0008150
	UniProtAcc	P27482

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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
810	CALML3	GSM4909285	Human	Breast	IDC	7.13e-60	9.22e-01	0.21
810	CALML3	GSM4909294	Human	Breast	IDC	2.90e-02	1.74e-01	0.2022
810	CALML3	brca2	Human	Breast	Precancer	8.15e-04	4.50e-02	-0.024
810	CALML3	brca3	Human	Breast	Precancer	9.34e-04	3.20e-02	-0.0263
810	CALML3	DCIS2	Human	Breast	DCIS	1.25e-16	1.58e-01	0.0085
810	CALML3	CA_HPV_1	Human	Cervix	CC	5.58e-13	-3.67e-01	0.0264
810	CALML3	HSIL_HPV_1	Human	Cervix	HSIL_HPV	2.20e-04	-3.20e-01	0.0116
810	CALML3	HSIL_HPV_2	Human	Cervix	HSIL_HPV	2.34e-12	-4.09e-01	0.0208
810	CALML3	N_HPV_1	Human	Cervix	N_HPV	1.38e-03	-3.67e-01	0.0079
810	CALML3	N_HPV_2	Human	Cervix	N_HPV	1.21e-03	4.65e-01	-0.0131
810	CALML3	CCII_1	Human	Cervix	CC	1.39e-06	-4.52e-01	0.3249
810	CALML3	Tumor	Human	Cervix	CC	2.60e-15	6.84e-01	0.1241
810	CALML3	sample3	Human	Cervix	CC	3.85e-21	5.92e-01	0.1387
810	CALML3	H2	Human	Cervix	HSIL_HPV	7.15e-03	-2.80e-01	0.0632
810	CALML3	T1	Human	Cervix	CC	1.98e-02	6.95e-02	0.0918
810	CALML3	T3	Human	Cervix	CC	7.32e-17	5.94e-01	0.1389
810	CALML3	LZE2T	Human	Esophagus	ESCC	3.13e-05	1.53e+00	0.082
810	CALML3	LZE4T	Human	Esophagus	ESCC	5.19e-34	2.57e+00	0.0811
810	CALML3	LZE7T	Human	Esophagus	ESCC	8.79e-14	2.20e+00	0.0667
810	CALML3	LZE20T	Human	Esophagus	ESCC	1.58e-09	1.34e+00	0.0662

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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

∗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
Thyroid	PTC
Thyroid	goiters
Thyroid	ATC

∗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

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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

CALML3

SNV

Missense_Mutation

c.91N>T

p.Arg31Cys

p.R31C

P27482

protein_coding

deleterious_low_confidence(0)

benign(0.046)

TCGA-D8-A142-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamid

CALML3

insertion

Frame_Shift_Ins

novel

c.436_437insTTCA

p.Val147HisfsTer47

p.V147Hfs*47

P27482

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

CALML3

SNV

Missense_Mutation

c.58N>A

p.Phe20Ile

p.F20I

P27482

protein_coding

deleterious_low_confidence(0.01)

benign(0.406)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CALML3

SNV

Missense_Mutation

c.219N>T

p.Met73Ile

p.M73I

P27482

protein_coding

deleterious_low_confidence(0.03)

benign(0.122)

TCGA-G4-6309-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

xeloda

CALML3

SNV

Missense_Mutation

c.134C>T

p.Thr45Met

p.T45M

P27482

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.717)

TCGA-EI-6882-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

CALML3

SNV

Missense_Mutation

c.220N>A

p.Ala74Thr

p.A74T

P27482

protein_coding

deleterious_low_confidence(0.03)

benign(0.036)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CALML3

SNV

Missense_Mutation

novel

c.152N>G

p.Asp51Gly

p.D51G

P27482

protein_coding

tolerated_low_confidence(0.06)

benign(0.001)

TCGA-AP-A0LD-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CALML3

SNV

Missense_Mutation

novel

c.51C>A

p.Phe17Leu

p.F17L

P27482

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.953)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CALML3

SNV

Missense_Mutation

rs754327442

c.379C>T

p.Arg127Trp

p.R127W

P27482

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.989)

TCGA-BG-A0MQ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CALML3

SNV

Missense_Mutation

rs752809700

c.386N>T

p.Ala129Val

p.A129V

P27482

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.715)

TCGA-BG-A220-01

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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