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: CAMTA1

Gene summary for CAMTA1

Gene summary.

Gene information	Species	Human
	Gene symbol	CAMTA1
	Gene ID	23261
	Gene name	calmodulin binding transcription activator 1
	Gene Alias	CANPMR
	Cytomap	1p36.31-p36.23
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q9Y6Y1

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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
23261	CAMTA1	GSM4909281	Human	Breast	IDC	1.31e-12	4.23e-01	0.21
23261	CAMTA1	GSM4909288	Human	Breast	IDC	1.13e-03	-2.89e-01	0.0988
23261	CAMTA1	GSM4909293	Human	Breast	IDC	3.63e-03	-1.55e-01	0.1581
23261	CAMTA1	GSM4909294	Human	Breast	IDC	3.53e-02	-4.70e-02	0.2022
23261	CAMTA1	GSM4909296	Human	Breast	IDC	1.17e-07	-2.65e-01	0.1524
23261	CAMTA1	GSM4909297	Human	Breast	IDC	1.03e-18	-2.52e-01	0.1517
23261	CAMTA1	GSM4909298	Human	Breast	IDC	5.38e-05	-2.64e-01	0.1551
23261	CAMTA1	GSM4909304	Human	Breast	IDC	2.32e-02	-2.50e-01	0.1636
23261	CAMTA1	GSM4909311	Human	Breast	IDC	1.10e-38	-6.28e-01	0.1534
23261	CAMTA1	GSM4909312	Human	Breast	IDC	1.15e-20	-5.37e-01	0.1552
23261	CAMTA1	GSM4909313	Human	Breast	IDC	7.34e-04	-1.27e-01	0.0391
23261	CAMTA1	GSM4909319	Human	Breast	IDC	1.03e-47	-5.39e-01	0.1563
23261	CAMTA1	GSM4909320	Human	Breast	IDC	1.41e-09	-4.93e-01	0.1575
23261	CAMTA1	GSM4909321	Human	Breast	IDC	4.01e-30	-5.84e-01	0.1559
23261	CAMTA1	brca3	Human	Breast	Precancer	2.80e-03	8.12e-02	-0.0263
23261	CAMTA1	M1	Human	Breast	IDC	3.57e-06	-4.46e-01	0.1577
23261	CAMTA1	NCCBC14	Human	Breast	DCIS	2.90e-16	-3.45e-01	0.2021
23261	CAMTA1	NCCBC2	Human	Breast	DCIS	1.65e-06	-5.97e-01	0.1554
23261	CAMTA1	NCCBC3	Human	Breast	DCIS	4.78e-03	-3.06e-01	0.1198
23261	CAMTA1	NCCBC5	Human	Breast	DCIS	2.81e-17	-4.20e-01	0.2046

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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
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
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:00163114	Colorectum	CRC	dephosphorylation	79/2078	417/18723	1.27e-06	7.21e-05	79
GO:00064705	Colorectum	CRC	protein dephosphorylation	57/2078	281/18723	4.49e-06	1.87e-04	57
GO:00353035	Colorectum	CRC	regulation of dephosphorylation	30/2078	128/18723	5.27e-05	1.20e-03	30
GO:0097720	Colorectum	CRC	calcineurin-mediated signaling	13/2078	48/18723	1.72e-03	1.77e-02	13
GO:00353045	Colorectum	CRC	regulation of protein dephosphorylation	20/2078	90/18723	1.77e-03	1.82e-02	20
GO:0033173	Colorectum	CRC	calcineurin-NFAT signaling cascade	12/2078	43/18723	1.93e-03	1.96e-02	12
GO:00480161	Colorectum	CRC	inositol phosphate-mediated signaling	14/2078	55/18723	2.21e-03	2.15e-02	14
GO:0070884	Colorectum	CRC	regulation of calcineurin-NFAT signaling cascade	10/2078	34/18723	2.96e-03	2.66e-02	10
GO:0106056	Colorectum	CRC	regulation of calcineurin-mediated signaling	10/2078	35/18723	3.74e-03	3.14e-02	10
GO:00353062	Colorectum	CRC	positive regulation of dephosphorylation	14/2078	59/18723	4.42e-03	3.47e-02	14
GO:000647017	Esophagus	HGIN	protein dephosphorylation	61/2587	281/18723	1.86e-04	3.51e-03	61
GO:003530425	Esophagus	HGIN	regulation of protein dephosphorylation	24/2587	90/18723	9.27e-04	1.17e-02	24
GO:003530320	Esophagus	HGIN	regulation of dephosphorylation	29/2587	128/18723	4.41e-03	3.87e-02	29
GO:001631110	Esophagus	ESCC	dephosphorylation	251/8552	417/18723	1.26e-09	2.99e-08	251
GO:000647018	Esophagus	ESCC	protein dephosphorylation	177/8552	281/18723	3.13e-09	6.72e-08	177
GO:0035304111	Esophagus	ESCC	regulation of protein dephosphorylation	66/8552	90/18723	8.82e-08	1.48e-06	66
GO:0035303111	Esophagus	ESCC	regulation of dephosphorylation	88/8552	128/18723	1.04e-07	1.71e-06	88
GO:00353074	Esophagus	ESCC	positive regulation of protein dephosphorylation	31/8552	45/18723	1.40e-03	6.62e-03	31
GO:00353066	Esophagus	ESCC	positive regulation of dephosphorylation	38/8552	59/18723	2.86e-03	1.21e-02	38
GO:00353047	Liver	Cirrhotic	regulation of protein dephosphorylation	39/4634	90/18723	8.57e-05	9.25e-04	39

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

CAMTA1

SNV

Missense_Mutation

c.4546N>G

p.Leu1516Val

p.L1516V

Q9Y6Y1

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

CAMTA1

SNV

Missense_Mutation

c.2635N>C

p.Glu879Gln

p.E879Q

Q9Y6Y1

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A8-A0A7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CAMTA1

SNV

Missense_Mutation

novel

c.148A>C

p.Lys50Gln

p.K50Q

Q9Y6Y1

protein_coding

deleterious(0)

probably_damaging(0.915)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CAMTA1

SNV

Missense_Mutation

novel

c.1369N>T

p.Pro457Ser

p.P457S

Q9Y6Y1

protein_coding

tolerated_low_confidence(0.35)

benign(0.003)

TCGA-B6-A3ZX-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

CAMTA1

SNV

Missense_Mutation

c.860C>G

p.Ser287Trp

p.S287W

Q9Y6Y1

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

CAMTA1

SNV

Missense_Mutation

novel

c.4383C>G

p.Asn1461Lys

p.N1461K

Q9Y6Y1

protein_coding

tolerated(0.05)

benign(0.025)

TCGA-BH-A18V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CAMTA1

SNV

Missense_Mutation

c.3028N>A

p.Gly1010Ser

p.G1010S

Q9Y6Y1

protein_coding

tolerated(0.4)

benign(0.014)

TCGA-C8-A12V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CAMTA1

SNV

Missense_Mutation

c.403G>C

p.Glu135Gln

p.E135Q

Q9Y6Y1

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CAMTA1

SNV

Missense_Mutation

rs771378439

c.1246G>A

p.Ala416Thr

p.A416T

Q9Y6Y1

protein_coding

tolerated_low_confidence(0.13)

benign(0.001)

TCGA-LL-A7T0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CAMTA1

insertion

Frame_Shift_Ins

novel

c.1291_1292insAGAAAAGAAAAACCATCAGAGTTATAAT

p.Leu431GlnfsTer17

p.L431Qfs*17

Q9Y6Y1

protein_coding

TCGA-A2-A0EQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

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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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