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	HTA11_2487_2000001011	Human	Colorectum	SER	5.15e-03	1.88e-01	-0.1808
80279	CDK5RAP3	HTA11_78_2000001011	Human	Colorectum	AD	3.71e-03	2.30e-01	-0.1088
80279	CDK5RAP3	HTA11_347_2000001011	Human	Colorectum	AD	2.44e-07	2.32e-01	-0.1954
80279	CDK5RAP3	HTA11_411_2000001011	Human	Colorectum	SER	2.94e-02	4.83e-01	-0.2602
80279	CDK5RAP3	HTA11_83_2000001011	Human	Colorectum	SER	3.04e-03	1.89e-01	-0.1526
80279	CDK5RAP3	HTA11_696_2000001011	Human	Colorectum	AD	9.34e-04	2.48e-01	-0.1464
80279	CDK5RAP3	HTA11_1391_2000001011	Human	Colorectum	AD	3.82e-08	3.86e-01	-0.059
80279	CDK5RAP3	HTA11_866_3004761011	Human	Colorectum	AD	1.65e-05	2.61e-01	0.096
80279	CDK5RAP3	HTA11_4255_2000001011	Human	Colorectum	SER	4.01e-03	2.84e-01	0.0446
80279	CDK5RAP3	HTA11_99999970781_79442	Human	Colorectum	MSS	5.76e-04	2.95e-01	0.294
80279	CDK5RAP3	HTA11_99999971662_82457	Human	Colorectum	MSS	2.02e-11	5.41e-01	0.3859
80279	CDK5RAP3	HTA11_99999974143_84620	Human	Colorectum	MSS	2.06e-08	4.05e-01	0.3005
80279	CDK5RAP3	A015-C-203	Human	Colorectum	FAP	3.80e-06	3.77e-01	-0.1294
80279	CDK5RAP3	A015-C-006	Human	Colorectum	FAP	2.12e-07	5.33e-01	-0.0994
80279	CDK5RAP3	A015-C-104	Human	Colorectum	FAP	1.22e-08	4.20e-01	-0.1899
80279	CDK5RAP3	A018-E-020	Human	Colorectum	FAP	6.60e-03	3.23e-01	-0.2034
80279	CDK5RAP3	LZE2T	Human	Esophagus	ESCC	2.94e-10	3.56e-01	0.082
80279	CDK5RAP3	LZE4T	Human	Esophagus	ESCC	4.96e-12	2.06e-01	0.0811
80279	CDK5RAP3	LZE5T	Human	Esophagus	ESCC	2.26e-05	3.10e-01	0.0514
80279	CDK5RAP3	LZE7T	Human	Esophagus	ESCC	4.23e-11	6.73e-01	0.0667

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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:00109721	Esophagus	ESCC	negative regulation of G2/M transition of mitotic cell cycle	41/8552	60/18723	3.25e-04	1.91e-03	41
GO:19027501	Esophagus	ESCC	negative regulation of cell cycle G2/M phase transition	42/8552	62/18723	3.69e-04	2.14e-03	42
GO:0043409110	Esophagus	ESCC	negative regulation of MAPK cascade	105/8552	180/18723	4.13e-04	2.35e-03	105
GO:00434055	Esophagus	ESCC	regulation of MAP kinase activity	102/8552	177/18723	8.89e-04	4.55e-03	102
GO:00448181	Esophagus	ESCC	mitotic G2/M transition checkpoint	32/8552	46/18723	9.01e-04	4.61e-03	32
GO:001092115	Esophagus	ESCC	regulation of phosphatase activity	52/8552	84/18723	1.98e-03	8.90e-03	52
GO:00434332	Esophagus	ESCC	negative regulation of DNA-binding transcription factor activity	103/8552	185/18723	3.86e-03	1.57e-02	103
GO:1901798111	Esophagus	ESCC	positive regulation of signal transduction by p53 class mediator	18/8552	25/18723	7.04e-03	2.56e-02	18
GO:00070951	Esophagus	ESCC	mitotic G2 DNA damage checkpoint	23/8552	34/18723	8.06e-03	2.86e-02	23
GO:00320882	Esophagus	ESCC	negative regulation of NF-kappaB transcription factor activity	54/8552	93/18723	1.08e-02	3.67e-02	54
GO:00434074	Esophagus	ESCC	negative regulation of MAP kinase activity	36/8552	59/18723	1.27e-02	4.21e-02	36
GO:004217612	Liver	Cirrhotic	regulation of protein catabolic process	181/4634	391/18723	7.94e-21	2.77e-18	181
GO:00349767	Liver	Cirrhotic	response to endoplasmic reticulum stress	130/4634	256/18723	1.72e-19	3.86e-17	130
GO:00359667	Liver	Cirrhotic	response to topologically incorrect protein	91/4634	159/18723	2.07e-18	3.60e-16	91
GO:190336212	Liver	Cirrhotic	regulation of cellular protein catabolic process	124/4634	255/18723	9.85e-17	1.26e-14	124
GO:00069867	Liver	Cirrhotic	response to unfolded protein	79/4634	137/18723	1.99e-16	2.49e-14	79
GO:000188912	Liver	Cirrhotic	liver development	81/4634	147/18723	2.99e-15	3.35e-13	81
GO:006100812	Liver	Cirrhotic	hepaticobiliary system development	82/4634	150/18723	3.72e-15	4.09e-13	82
GO:00224117	Liver	Cirrhotic	cellular component disassembly	182/4634	443/18723	1.59e-14	1.54e-12	182
GO:190382912	Liver	Cirrhotic	positive regulation of cellular protein localization	123/4634	276/18723	4.06e-13	3.22e-11	123

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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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