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: CDK5RAP3

Gene summary for CDK5RAP3

Gene summary.

Gene information	Species	Human
	Gene symbol	CDK5RAP3
	Gene ID	80279
	Gene name	CDK5 regulatory subunit associated protein 3
	Gene Alias	C53
	Cytomap	17q21.32
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q96JB5

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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
80279	CDK5RAP3	SYSMH3	Human	Oral cavity	OSCC	6.06e-29	5.84e-01	0.2442
80279	CDK5RAP3	SYSMH4	Human	Oral cavity	OSCC	1.46e-04	6.00e-02	0.1226
80279	CDK5RAP3	SYSMH5	Human	Oral cavity	OSCC	4.00e-10	3.21e-01	0.0647
80279	CDK5RAP3	SYSMH6	Human	Oral cavity	OSCC	4.02e-13	3.57e-01	0.1275
80279	CDK5RAP3	P4_S8_cSCC	Human	Skin	cSCC	5.50e-03	4.74e-02	-0.3095
80279	CDK5RAP3	P5_S10_cSCC	Human	Skin	cSCC	1.22e-05	9.42e-03	-0.299
80279	CDK5RAP3	P1_cSCC	Human	Skin	cSCC	1.89e-20	7.99e-01	0.0292
80279	CDK5RAP3	P2_cSCC	Human	Skin	cSCC	1.35e-14	4.50e-01	-0.024
80279	CDK5RAP3	P4_cSCC	Human	Skin	cSCC	2.77e-26	5.74e-01	-0.00290000000000005
80279	CDK5RAP3	P10_cSCC	Human	Skin	cSCC	1.21e-20	6.12e-01	0.1017
80279	CDK5RAP3	cSCC_p9	Human	Skin	cSCC	4.37e-03	-5.65e-02	-0.1991
80279	CDK5RAP3	male-WTA	Human	Thyroid	PTC	2.34e-03	-1.80e-01	0.1037
80279	CDK5RAP3	PTC01	Human	Thyroid	PTC	3.25e-17	2.88e-01	0.1899
80279	CDK5RAP3	PTC03	Human	Thyroid	PTC	1.02e-07	2.03e-01	0.1784
80279	CDK5RAP3	PTC04	Human	Thyroid	PTC	4.74e-24	3.23e-01	0.1927
80279	CDK5RAP3	PTC05	Human	Thyroid	PTC	1.03e-18	7.60e-01	0.2065
80279	CDK5RAP3	PTC06	Human	Thyroid	PTC	2.74e-34	7.39e-01	0.2057
80279	CDK5RAP3	PTC07	Human	Thyroid	PTC	4.09e-44	6.02e-01	0.2044
80279	CDK5RAP3	ATC09	Human	Thyroid	ATC	2.11e-09	2.84e-01	0.2871
80279	CDK5RAP3	ATC12	Human	Thyroid	ATC	1.03e-30	6.39e-01	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:1903362	Colorectum	AD	regulation of cellular protein catabolic process	109/3918	255/18723	2.14e-15	6.08e-13	109
GO:0009895	Colorectum	AD	negative regulation of catabolic process	124/3918	320/18723	1.66e-13	3.35e-11	124
GO:1903829	Colorectum	AD	positive regulation of cellular protein localization	110/3918	276/18723	4.58e-13	8.44e-11	110
GO:0031330	Colorectum	AD	negative regulation of cellular catabolic process	104/3918	262/18723	2.66e-12	3.96e-10	104
GO:0048732	Colorectum	AD	gland development	149/3918	436/18723	6.07e-11	6.33e-09	149
GO:0022411	Colorectum	AD	cellular component disassembly	147/3918	443/18723	8.53e-10	6.76e-08	147
GO:0042177	Colorectum	AD	negative regulation of protein catabolic process	55/3918	121/18723	1.19e-09	8.85e-08	55
GO:1903363	Colorectum	AD	negative regulation of cellular protein catabolic process	39/3918	75/18723	2.69e-09	1.87e-07	39
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90
GO:1903320	Colorectum	AD	regulation of protein modification by small protein conjugation or removal	86/3918	242/18723	9.43e-08	4.65e-06	86
GO:1900180	Colorectum	AD	regulation of protein localization to nucleus	55/3918	136/18723	1.70e-07	7.34e-06	55
GO:0034101	Colorectum	AD	erythrocyte homeostasis	51/3918	129/18723	1.07e-06	3.59e-05	51
GO:0030099	Colorectum	AD	myeloid cell differentiation	119/3918	381/18723	1.24e-06	4.01e-05	119
GO:1900182	Colorectum	AD	positive regulation of protein localization to nucleus	38/3918	87/18723	1.43e-06	4.52e-05	38
GO:0034504	Colorectum	AD	protein localization to nucleus	94/3918	290/18723	2.83e-06	8.09e-05	94
GO:0031396	Colorectum	AD	regulation of protein ubiquitination	72/3918	210/18723	4.50e-06	1.21e-04	72
GO:0002262	Colorectum	AD	myeloid cell homeostasis	57/3918	157/18723	6.17e-06	1.56e-04	57
GO:0061008	Colorectum	AD	hepaticobiliary system development	55/3918	150/18723	6.34e-06	1.59e-04	55
GO:0001889	Colorectum	AD	liver development	54/3918	147/18723	7.20e-06	1.77e-04	54

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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

CDK5RAP3

SNV

Missense_Mutation

novel

c.814N>T

p.Pro272Ser

p.P272S

Q96JB5

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

CDK5RAP3

SNV

Missense_Mutation

novel

c.1164C>A

p.Phe388Leu

p.F388L

Q96JB5

protein_coding

deleterious(0.03)

probably_damaging(0.997)

TCGA-A2-A3XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

CDK5RAP3

SNV

Missense_Mutation

novel

c.371N>G

p.Glu124Gly

p.E124G

Q96JB5

protein_coding

deleterious(0)

possibly_damaging(0.894)

TCGA-C8-A273-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CDK5RAP3

SNV

Missense_Mutation

novel

c.371N>G

p.Glu124Gly

p.E124G

Q96JB5

protein_coding

deleterious(0)

possibly_damaging(0.894)

TCGA-E9-A1NF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CDK5RAP3

insertion

Frame_Shift_Ins

novel

c.354_355insGGCCC

p.Met119GlyfsTer3

p.M119Gfs*3

Q96JB5

protein_coding

TCGA-BH-A0DS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide

CDK5RAP3

insertion

Nonsense_Mutation

novel

c.355_356insGACTTTGAGAGGTCAGTCCCAT

p.Met119ArgfsTer3

p.M119Rfs*3

Q96JB5

protein_coding

TCGA-BH-A0DS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide

CDK5RAP3

deletion

Frame_Shift_Del

novel

c.528delN

p.Ala177GlnfsTer32

p.A177Qfs*32

Q96JB5

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CDK5RAP3

SNV

Missense_Mutation

c.832C>T

p.Pro278Ser

p.P278S

Q96JB5

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-C5-A7CO-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

CDK5RAP3

SNV

Missense_Mutation

c.530N>A

p.Ala177Glu

p.A177E

Q96JB5

protein_coding

tolerated(0.94)

benign(0.148)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

CDK5RAP3

SNV

Missense_Mutation

c.450G>T

p.Glu150Asp

p.E150D

Q96JB5

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

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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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