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:1903362111	Esophagus	ESCC	regulation of cellular protein catabolic process	188/8552	255/18723	5.12e-20	6.62e-18	188
GO:1903829111	Esophagus	ESCC	positive regulation of cellular protein localization	199/8552	276/18723	2.99e-19	3.45e-17	199
GO:004477216	Esophagus	ESCC	mitotic cell cycle phase transition	281/8552	424/18723	4.63e-18	4.45e-16	281
GO:0035966111	Esophagus	ESCC	response to topologically incorrect protein	125/8552	159/18723	1.44e-17	1.27e-15	125
GO:0031396111	Esophagus	ESCC	regulation of protein ubiquitination	154/8552	210/18723	2.70e-16	2.04e-14	154
GO:000734615	Esophagus	ESCC	regulation of mitotic cell cycle	293/8552	457/18723	8.00e-16	5.64e-14	293
GO:0006986111	Esophagus	ESCC	response to unfolded protein	107/8552	137/18723	7.01e-15	3.87e-13	107
GO:0072331111	Esophagus	ESCC	signal transduction by p53 class mediator	121/8552	163/18723	9.61e-14	4.69e-12	121
GO:0035967111	Esophagus	ESCC	cellular response to topologically incorrect protein	90/8552	116/18723	1.94e-12	8.11e-11	90
GO:0010563111	Esophagus	ESCC	negative regulation of phosphorus metabolic process	274/8552	442/18723	2.32e-12	9.41e-11	274
GO:190018018	Esophagus	ESCC	regulation of protein localization to nucleus	102/8552	136/18723	2.84e-12	1.13e-10	102
GO:0045936111	Esophagus	ESCC	negative regulation of phosphate metabolic process	273/8552	441/18723	3.18e-12	1.25e-10	273
GO:0048732111	Esophagus	ESCC	gland development	269/8552	436/18723	7.81e-12	2.95e-10	269
GO:0051348111	Esophagus	ESCC	negative regulation of transferase activity	177/8552	268/18723	1.08e-11	4.00e-10	177
GO:007190016	Esophagus	ESCC	regulation of protein serine/threonine kinase activity	227/8552	359/18723	1.12e-11	4.10e-10	227
GO:190018217	Esophagus	ESCC	positive regulation of protein localization to nucleus	70/8552	87/18723	2.63e-11	8.99e-10	70
GO:190198713	Esophagus	ESCC	regulation of cell cycle phase transition	242/8552	390/18723	3.86e-11	1.26e-09	242
GO:190199013	Esophagus	ESCC	regulation of mitotic cell cycle phase transition	191/8552	299/18723	1.35e-10	3.94e-09	191
GO:0042326111	Esophagus	ESCC	negative regulation of phosphorylation	237/8552	385/18723	1.86e-10	5.33e-09	237
GO:0034620111	Esophagus	ESCC	cellular response to unfolded protein	74/8552	96/18723	3.10e-10	8.66e-09	74

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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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