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: CAMK1D

Gene summary for CAMK1D

Gene summary.

Gene information	Species	Human
	Gene symbol	CAMK1D
	Gene ID	57118
	Gene name	calcium/calmodulin dependent protein kinase ID
	Gene Alias	CKLiK
	Cytomap	10p13
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	Q5SQQ7

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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
57118	CAMK1D	CCI_1	Human	Cervix	CC	6.43e-13	1.20e+00	0.528
57118	CAMK1D	CCI_3	Human	Cervix	CC	1.90e-11	9.97e-01	0.516
57118	CAMK1D	L1	Human	Cervix	CC	2.14e-02	-1.89e-01	0.0802
57118	CAMK1D	HTA11_1938_2000001011	Human	Colorectum	AD	7.25e-05	5.68e-01	-0.0811
57118	CAMK1D	HTA11_347_2000001011	Human	Colorectum	AD	7.51e-36	1.30e+00	-0.1954
57118	CAMK1D	HTA11_411_2000001011	Human	Colorectum	SER	1.23e-06	6.48e-01	-0.2602
57118	CAMK1D	HTA11_83_2000001011	Human	Colorectum	SER	1.43e-02	4.61e-01	-0.1526
57118	CAMK1D	HTA11_866_2000001011	Human	Colorectum	AD	1.70e-14	7.22e-01	-0.1001
57118	CAMK1D	HTA11_1391_2000001011	Human	Colorectum	AD	1.49e-02	5.12e-01	-0.059
57118	CAMK1D	HTA11_2992_2000001011	Human	Colorectum	SER	1.08e-07	5.79e-01	-0.1706
57118	CAMK1D	HTA11_546_2000001011	Human	Colorectum	AD	3.59e-06	5.58e-01	-0.0842
57118	CAMK1D	HTA11_7663_2000001011	Human	Colorectum	SER	6.23e-03	5.34e-01	0.0131
57118	CAMK1D	HTA11_10623_2000001011	Human	Colorectum	AD	1.71e-03	5.96e-01	-0.0177
57118	CAMK1D	HTA11_7696_3000711011	Human	Colorectum	AD	1.29e-02	3.95e-01	0.0674
57118	CAMK1D	HTA11_6818_2000001011	Human	Colorectum	AD	3.53e-03	5.14e-01	0.0112
57118	CAMK1D	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.07e-05	6.79e-01	0.3487
57118	CAMK1D	HTA11_99999965104_69814	Human	Colorectum	MSS	2.21e-08	8.17e-01	0.281
57118	CAMK1D	HTA11_99999973899_84307	Human	Colorectum	MSS	1.62e-06	-6.92e-01	0.2585
57118	CAMK1D	HTA11_99999974143_84620	Human	Colorectum	MSS	5.20e-71	-1.27e+00	0.3005
57118	CAMK1D	A001-C-207	Human	Colorectum	FAP	7.03e-06	-3.99e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
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:00321035	Cervix	CC	positive regulation of response to external stimulus	95/2311	427/18723	5.44e-09	5.03e-07	95
GO:00603267	Cervix	CC	cell chemotaxis	73/2311	310/18723	2.82e-08	1.96e-06	73
GO:00975298	Cervix	CC	myeloid leukocyte migration	56/2311	220/18723	7.21e-08	4.15e-06	56
GO:00305957	Cervix	CC	leukocyte chemotaxis	57/2311	230/18723	1.48e-07	7.07e-06	57
GO:00716218	Cervix	CC	granulocyte chemotaxis	37/2311	125/18723	2.16e-07	9.56e-06	37
GO:00163587	Cervix	CC	dendrite development	58/2311	243/18723	4.52e-07	1.76e-05	58
GO:00509007	Cervix	CC	leukocyte migration	78/2311	369/18723	1.09e-06	3.80e-05	78
GO:00975308	Cervix	CC	granulocyte migration	39/2311	148/18723	2.67e-06	7.87e-05	39
GO:00026857	Cervix	CC	regulation of leukocyte migration	50/2311	210/18723	2.95e-06	8.31e-05	50
GO:00026888	Cervix	CC	regulation of leukocyte chemotaxis	34/2311	122/18723	3.00e-06	8.38e-05	34
GO:00305938	Cervix	CC	neutrophil chemotaxis	30/2311	103/18723	4.24e-06	1.09e-04	30
GO:00109757	Cervix	CC	regulation of neuron projection development	88/2311	445/18723	4.26e-06	1.09e-04	88
GO:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:00509203	Cervix	CC	regulation of chemotaxis	51/2311	223/18723	8.03e-06	1.86e-04	51
GO:00313467	Cervix	CC	positive regulation of cell projection organization	72/2311	353/18723	1.04e-05	2.32e-04	72
GO:00026878	Cervix	CC	positive regulation of leukocyte migration	35/2311	135/18723	1.25e-05	2.60e-04	35
GO:19902666	Cervix	CC	neutrophil migration	32/2311	122/18723	2.25e-05	4.00e-04	32
GO:00026906	Cervix	CC	positive regulation of leukocyte chemotaxis	26/2311	94/18723	4.85e-05	7.34e-04	26
GO:00181057	Cervix	CC	peptidyl-serine phosphorylation	63/2311	315/18723	6.65e-05	9.47e-04	63
GO:00457306	Cervix	CC	respiratory burst	14/2311	37/18723	6.97e-05	9.81e-04	14

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa052148	Cervix	CC	Glioma	24/1267	75/8465	1.51e-04	9.20e-04	5.44e-04	24
hsa049218	Cervix	CC	Oxytocin signaling pathway	34/1267	154/8465	1.12e-02	3.42e-02	2.02e-02	34
hsa0521414	Cervix	CC	Glioma	24/1267	75/8465	1.51e-04	9.20e-04	5.44e-04	24
hsa0492111	Cervix	CC	Oxytocin signaling pathway	34/1267	154/8465	1.12e-02	3.42e-02	2.02e-02	34
hsa04925	Colorectum	FAP	Aldosterone synthesis and secretion	25/1404	98/8465	1.55e-02	4.99e-02	3.04e-02	25
hsa049251	Colorectum	FAP	Aldosterone synthesis and secretion	25/1404	98/8465	1.55e-02	4.99e-02	3.04e-02	25
hsa049252	Colorectum	CRC	Aldosterone synthesis and secretion	22/1091	98/8465	5.92e-03	3.00e-02	2.03e-02	22
hsa049253	Colorectum	CRC	Aldosterone synthesis and secretion	22/1091	98/8465	5.92e-03	3.00e-02	2.03e-02	22
hsa0521417	Esophagus	ESCC	Glioma	52/4205	75/8465	4.20e-04	1.45e-03	7.43e-04	52
hsa0521418	Esophagus	ESCC	Glioma	52/4205	75/8465	4.20e-04	1.45e-03	7.43e-04	52
hsa052142	Liver	HCC	Glioma	47/4020	75/8465	5.67e-03	1.62e-02	9.02e-03	47
hsa0521411	Liver	HCC	Glioma	47/4020	75/8465	5.67e-03	1.62e-02	9.02e-03	47
hsa04921	Lung	IAC	Oxytocin signaling pathway	33/1053	154/8465	1.09e-03	7.82e-03	5.19e-03	33
hsa052146	Lung	IAC	Glioma	18/1053	75/8465	4.07e-03	1.94e-02	1.29e-02	18
hsa049211	Lung	IAC	Oxytocin signaling pathway	33/1053	154/8465	1.09e-03	7.82e-03	5.19e-03	33
hsa0521412	Lung	IAC	Glioma	18/1053	75/8465	4.07e-03	1.94e-02	1.29e-02	18
hsa0521421	Lung	AIS	Glioma	17/961	75/8465	3.76e-03	2.00e-02	1.28e-02	17
hsa052143	Lung	AIS	Glioma	17/961	75/8465	3.76e-03	2.00e-02	1.28e-02	17
hsa049214	Lung	AAH	Oxytocin signaling pathway	17/348	154/8465	1.87e-04	8.70e-03	6.99e-03	17
hsa049215	Lung	AAH	Oxytocin signaling pathway	17/348	154/8465	1.87e-04	8.70e-03	6.99e-03	17

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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

CAMK1D

SNV

Missense_Mutation

novel

c.343N>G

p.Phe115Val

p.F115V

Q8IU85

protein_coding

tolerated(0.51)

probably_damaging(0.999)

TCGA-A2-A04T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

CAMK1D

SNV

Missense_Mutation

novel

c.691N>C

p.Glu231Gln

p.E231Q

Q8IU85

protein_coding

tolerated(0.12)

probably_damaging(0.922)

TCGA-A2-A0CO-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CAMK1D

insertion

Frame_Shift_Ins

novel

c.194_195insGAAATGGAAA

p.Ser65ArgfsTer8

p.S65Rfs*8

Q8IU85

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CAMK1D

insertion

Frame_Shift_Ins

novel

c.196_197insAATGTGAATTTTCTCT

p.Ile66LysfsTer9

p.I66Kfs*9

Q8IU85

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CAMK1D

insertion

Nonsense_Mutation

novel

c.205_206insTGTGTGGCAAGTGGTACCGGGAGGTGGCCTAACCGTGTTGACCTCC

p.Glu69ValfsTer11

p.E69Vfs*11

Q8IU85

protein_coding

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CAMK1D

insertion

Nonsense_Mutation

novel

c.201_202insTCCAGTGTTTGCAGAGCGCTCTGAAATTTCCTCTAGATGAAA

p.Glu67_Asn68insSerSerValCysArgAlaLeuTerAsnPheLeuTerMetLys

p.E67_N68insSSVCRAL*NFL*MK

Q8IU85

protein_coding

TCGA-A8-A0A1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

CAMK1D

SNV

Missense_Mutation

rs752176853

c.442N>A

p.Glu148Lys

p.E148K

Q8IU85

protein_coding

deleterious(0.03)

benign(0.255)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

CAMK1D

SNV

Missense_Mutation

c.830N>A

p.Pro277Gln

p.P277Q

Q8IU85

protein_coding

deleterious(0)

probably_damaging(0.965)

TCGA-A6-3809-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CAMK1D

SNV

Missense_Mutation

rs754487170

c.938N>T

p.Thr313Met

p.T313M

Q8IU85

protein_coding

deleterious(0)

probably_damaging(0.97)

TCGA-A6-6653-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CAMK1D

SNV

Missense_Mutation

c.707N>T

p.Ala236Val

p.A236V

Q8IU85

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-3713-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

5-fluorouracil

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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
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME		losartan	LOSARTAN	25410890
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME		ENTRECTINIB	ENTRECTINIB
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME	inhibitor	178102336	BOSUTINIB
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME		TCMDC-125758	CHEMBL546797
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME		ILORASERTIB	ILORASERTIB
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME		RG-1530	RG-1530
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME		TAE-684	TAE-684
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME		681640	CHEMBL379975
57118	CAMK1D	KINASE, SERINE THREONINE KINASE, TRANSCRIPTION FACTOR, ENZYME, DRUGGABLE GENOME		SOTRASTAURIN	SOTRASTAURIN

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