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: CALD1

Gene summary for CALD1

Gene summary.

Gene information	Species	Human
	Gene symbol	CALD1
	Gene ID	800
	Gene name	caldesmon 1
	Gene Alias	CDM
	Cytomap	7q33
	Gene Type	protein-coding
	GO ID	GO:0001525
	UniProtAcc	A0A140VKA0

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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
800	CALD1	GSM4909281	Human	Breast	IDC	2.99e-08	4.29e-01	0.21
800	CALD1	GSM4909285	Human	Breast	IDC	1.87e-05	-1.50e-02	0.21
800	CALD1	GSM4909286	Human	Breast	IDC	5.94e-08	1.41e-02	0.1081
800	CALD1	GSM4909291	Human	Breast	IDC	1.62e-09	-5.95e-01	0.1753
800	CALD1	GSM4909293	Human	Breast	IDC	1.11e-17	-5.29e-01	0.1581
800	CALD1	GSM4909294	Human	Breast	IDC	3.20e-14	-5.03e-01	0.2022
800	CALD1	GSM4909296	Human	Breast	IDC	2.61e-20	-5.80e-01	0.1524
800	CALD1	GSM4909297	Human	Breast	IDC	4.43e-24	-5.86e-01	0.1517
800	CALD1	GSM4909299	Human	Breast	IDC	3.78e-08	4.52e-01	0.035
800	CALD1	GSM4909301	Human	Breast	IDC	2.82e-27	-6.45e-01	0.1577
800	CALD1	GSM4909304	Human	Breast	IDC	3.59e-37	-6.63e-01	0.1636
800	CALD1	GSM4909306	Human	Breast	IDC	1.86e-07	-4.38e-01	0.1564
800	CALD1	GSM4909307	Human	Breast	IDC	3.87e-11	-7.93e-02	0.1569
800	CALD1	GSM4909308	Human	Breast	IDC	8.47e-14	-5.72e-01	0.158
800	CALD1	GSM4909311	Human	Breast	IDC	1.32e-24	-4.46e-01	0.1534
800	CALD1	GSM4909312	Human	Breast	IDC	4.96e-34	-6.68e-01	0.1552
800	CALD1	GSM4909315	Human	Breast	IDC	1.54e-26	-6.21e-01	0.21
800	CALD1	GSM4909316	Human	Breast	IDC	1.57e-07	-6.65e-01	0.21
800	CALD1	GSM4909318	Human	Breast	IDC	5.14e-05	-6.77e-01	0.2031
800	CALD1	GSM4909319	Human	Breast	IDC	1.53e-30	-6.61e-01	0.1563

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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
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:000701514	Breast	IDC	actin filament organization	55/1434	442/18723	2.45e-04	3.84e-03	55
GO:005101714	Breast	IDC	actin filament bundle assembly	24/1434	157/18723	8.73e-04	1.01e-02	24
GO:006157214	Breast	IDC	actin filament bundle organization	24/1434	161/18723	1.25e-03	1.33e-02	24
GO:00030125	Breast	IDC	muscle system process	50/1434	452/18723	5.52e-03	4.05e-02	50
GO:000701524	Breast	DCIS	actin filament organization	56/1390	442/18723	5.90e-05	1.19e-03	56
GO:005101724	Breast	DCIS	actin filament bundle assembly	25/1390	157/18723	2.31e-04	3.65e-03	25
GO:006157224	Breast	DCIS	actin filament bundle organization	25/1390	161/18723	3.43e-04	4.90e-03	25
GO:000301212	Breast	DCIS	muscle system process	50/1390	452/18723	3.02e-03	2.57e-02	50
GO:000701510	Cervix	CC	actin filament organization	109/2311	442/18723	4.92e-13	2.45e-10	109
GO:006157210	Cervix	CC	actin filament bundle organization	44/2311	161/18723	2.08e-07	9.34e-06	44
GO:005101710	Cervix	CC	actin filament bundle assembly	43/2311	157/18723	2.66e-07	1.12e-05	43
GO:000701515	Cervix	HSIL_HPV	actin filament organization	43/737	442/18723	4.77e-08	3.59e-06	43
GO:006157215	Cervix	HSIL_HPV	actin filament bundle organization	16/737	161/18723	6.30e-04	8.64e-03	16
GO:005101715	Cervix	HSIL_HPV	actin filament bundle assembly	15/737	157/18723	1.37e-03	1.56e-02	15
GO:000701516	Endometrium	AEH	actin filament organization	98/2100	442/18723	1.99e-11	2.98e-09	98
GO:005101716	Endometrium	AEH	actin filament bundle assembly	39/2100	157/18723	1.21e-06	3.91e-05	39
GO:006157216	Endometrium	AEH	actin filament bundle organization	39/2100	161/18723	2.36e-06	6.86e-05	39
GO:00030126	Endometrium	AEH	muscle system process	78/2100	452/18723	6.89e-05	1.06e-03	78
GO:0006936	Endometrium	AEH	muscle contraction	59/2100	347/18723	7.32e-04	6.99e-03	59
GO:000701517	Endometrium	EEC	actin filament organization	95/2168	442/18723	1.31e-09	1.09e-07	95

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa042704	Oral cavity	NEOLP	Vascular smooth muscle contraction	30/1112	134/8465	2.06e-03	8.97e-03	5.64e-03	30
hsa0427011	Oral cavity	NEOLP	Vascular smooth muscle contraction	30/1112	134/8465	2.06e-03	8.97e-03	5.64e-03	30

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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

CALD1

SNV

Missense_Mutation

c.1384N>A

p.Glu462Lys

p.E462K

Q05682

protein_coding

deleterious_low_confidence(0.05)

possibly_damaging(0.732)

TCGA-A2-A0EX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CALD1

SNV

Missense_Mutation

c.56N>A

p.Arg19Gln

p.R19Q

Q05682

protein_coding

deleterious(0)

probably_damaging(0.988)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CALD1

SNV

Missense_Mutation

c.1315N>C

p.Glu439Gln

p.E439Q

Q05682

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.898)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

CALD1

SNV

Missense_Mutation

c.1450C>G

p.Arg484Gly

p.R484G

Q05682

protein_coding

tolerated(0.24)

benign(0)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

CALD1

SNV

Missense_Mutation

c.232N>A

p.Glu78Lys

p.E78K

Q05682

protein_coding

deleterious(0.01)

possibly_damaging(0.652)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CALD1

SNV

Missense_Mutation

novel

c.1622N>T

p.Arg541Leu

p.R541L

Q05682

protein_coding

deleterious(0)

possibly_damaging(0.845)

TCGA-B6-A1KI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CALD1

SNV

Missense_Mutation

c.2026N>C

p.Asp676His

p.D676H

Q05682

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CALD1

SNV

Missense_Mutation

novel

c.1065N>T

p.Glu355Asp

p.E355D

Q05682

protein_coding

tolerated_low_confidence(0.37)

benign(0.096)

TCGA-E9-A54Y-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CALD1

SNV

Missense_Mutation

novel

c.2128N>G

p.Arg710Gly

p.R710G

Q05682

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-JL-A3YW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CALD1

SNV

Missense_Mutation

novel

c.2090C>T

p.Pro697Leu

p.P697L

Q05682

protein_coding

deleterious(0)

possibly_damaging(0.874)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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