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: CDK5RAP2

Gene summary for CDK5RAP2

Gene summary.

Gene information	Species	Human
	Gene symbol	CDK5RAP2
	Gene ID	55755
	Gene name	CDK5 regulatory subunit associated protein 2
	Gene Alias	C48
	Cytomap	9q33.2
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	B9EG74

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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
55755	CDK5RAP2	CCI_2	Human	Cervix	CC	4.59e-04	7.11e-01	0.5249
55755	CDK5RAP2	CCI_3	Human	Cervix	CC	4.36e-14	9.14e-01	0.516
55755	CDK5RAP2	LZE2T	Human	Esophagus	ESCC	2.31e-03	8.75e-01	0.082
55755	CDK5RAP2	LZE4T	Human	Esophagus	ESCC	3.61e-19	1.50e+00	0.0811
55755	CDK5RAP2	LZE7T	Human	Esophagus	ESCC	5.88e-10	4.21e-01	0.0667
55755	CDK5RAP2	LZE20T	Human	Esophagus	ESCC	4.79e-04	1.96e-01	0.0662
55755	CDK5RAP2	LZE24T	Human	Esophagus	ESCC	8.70e-05	8.03e-02	0.0596
55755	CDK5RAP2	LZE6T	Human	Esophagus	ESCC	1.40e-04	1.80e-01	0.0845
55755	CDK5RAP2	P1T-E	Human	Esophagus	ESCC	3.20e-07	4.08e-01	0.0875
55755	CDK5RAP2	P2T-E	Human	Esophagus	ESCC	1.23e-29	4.69e-01	0.1177
55755	CDK5RAP2	P4T-E	Human	Esophagus	ESCC	4.91e-11	2.67e-01	0.1323
55755	CDK5RAP2	P5T-E	Human	Esophagus	ESCC	3.42e-07	1.04e-01	0.1327
55755	CDK5RAP2	P8T-E	Human	Esophagus	ESCC	1.83e-11	1.77e-01	0.0889
55755	CDK5RAP2	P9T-E	Human	Esophagus	ESCC	2.94e-33	8.40e-01	0.1131
55755	CDK5RAP2	P10T-E	Human	Esophagus	ESCC	1.88e-13	1.71e-01	0.116
55755	CDK5RAP2	P11T-E	Human	Esophagus	ESCC	1.61e-02	1.82e-01	0.1426
55755	CDK5RAP2	P12T-E	Human	Esophagus	ESCC	2.34e-12	2.16e-01	0.1122
55755	CDK5RAP2	P15T-E	Human	Esophagus	ESCC	2.51e-33	1.50e+00	0.1149
55755	CDK5RAP2	P16T-E	Human	Esophagus	ESCC	2.91e-08	1.69e-01	0.1153
55755	CDK5RAP2	P17T-E	Human	Esophagus	ESCC	9.69e-08	3.46e-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
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
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:00311166	Prostate	BPH	positive regulation of microtubule polymerization	16/3107	33/18723	2.15e-05	2.60e-04	16
GO:19019904	Prostate	BPH	regulation of mitotic cell cycle phase transition	77/3107	299/18723	3.36e-05	3.77e-04	77
GO:001063916	Prostate	BPH	negative regulation of organelle organization	87/3107	348/18723	3.56e-05	3.90e-04	87
GO:00328862	Prostate	BPH	regulation of microtubule-based process	64/3107	240/18723	4.93e-05	5.11e-04	64
GO:19028505	Prostate	BPH	microtubule cytoskeleton organization involved in mitosis	43/3107	147/18723	8.78e-05	8.27e-04	43
GO:00311136	Prostate	BPH	regulation of microtubule polymerization	21/3107	55/18723	1.02e-04	9.39e-04	21
GO:00311126	Prostate	BPH	positive regulation of microtubule polymerization or depolymerization	16/3107	37/18723	1.22e-04	1.10e-03	16
GO:00457863	Prostate	BPH	negative regulation of cell cycle	91/3107	385/18723	2.10e-04	1.71e-03	91
GO:00459303	Prostate	BPH	negative regulation of mitotic cell cycle	60/3107	235/18723	3.00e-04	2.32e-03	60
GO:00467854	Prostate	BPH	microtubule polymerization	26/3107	83/18723	6.67e-04	4.48e-03	26
GO:19019874	Prostate	BPH	regulation of cell cycle phase transition	89/3107	390/18723	8.17e-04	5.34e-03	89
GO:19021154	Prostate	BPH	regulation of organelle assembly	48/3107	186/18723	8.91e-04	5.72e-03	48
GO:19019913	Prostate	BPH	negative regulation of mitotic cell cycle phase transition	46/3107	179/18723	1.24e-03	7.51e-03	46
GO:00108242	Prostate	BPH	regulation of centrosome duplication	16/3107	45/18723	1.62e-03	9.39e-03	16
GO:01400144	Prostate	BPH	mitotic nuclear division	67/3107	287/18723	1.87e-03	1.07e-02	67
GO:00311102	Prostate	BPH	regulation of microtubule polymerization or depolymerization	25/3107	88/18723	3.76e-03	1.89e-02	25
GO:00466053	Prostate	BPH	regulation of centrosome cycle	16/3107	49/18723	4.35e-03	2.14e-02	16
GO:00516531	Prostate	BPH	spindle localization	17/3107	56/18723	7.62e-03	3.39e-02	17
GO:0045664	Prostate	BPH	regulation of neuron differentiation	46/3107	196/18723	7.95e-03	3.47e-02	46
GO:00310231	Prostate	BPH	microtubule organizing center organization	35/3107	143/18723	9.88e-03	4.16e-02	35

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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

CDK5RAP2

SNV

Missense_Mutation

c.1209N>C

p.Lys403Asn

p.K403N

Q96SN8

protein_coding

deleterious(0.01)

possibly_damaging(0.601)

TCGA-A2-A04W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CDK5RAP2

SNV

Missense_Mutation

rs746903524

c.2836C>T

p.Arg946Trp

p.R946W

Q96SN8

protein_coding

deleterious(0.02)

benign(0.23)

TCGA-A2-A0YI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Femara

CDK5RAP2

SNV

Missense_Mutation

rs151280101

c.1488C>A

p.Phe496Leu

p.F496L

Q96SN8

protein_coding

tolerated(1)

benign(0)

TCGA-A2-A0YM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CDK5RAP2

SNV

Missense_Mutation

novel

c.4591N>A

p.Gln1531Lys

p.Q1531K

Q96SN8

protein_coding

tolerated(0.17)

benign(0.007)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

CDK5RAP2

SNV

Missense_Mutation

c.4539C>A

p.Ser1513Arg

p.S1513R

Q96SN8

protein_coding

tolerated(0.19)

benign(0.003)

TCGA-A7-A4SD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CDK5RAP2

SNV

Missense_Mutation

novel

c.920N>A

p.Ala307Asp

p.A307D

Q96SN8

protein_coding

deleterious(0.01)

possibly_damaging(0.532)

TCGA-A7-A6VV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

CDK5RAP2

SNV

Missense_Mutation

c.1201A>C

p.Ile401Leu

p.I401L

Q96SN8

protein_coding

tolerated(0.19)

benign(0.006)

TCGA-AN-A0AR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CDK5RAP2

SNV

Missense_Mutation

c.1894T>G

p.Tyr632Asp

p.Y632D

Q96SN8

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-B6-A0I9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CDK5RAP2

SNV

Missense_Mutation

novel

c.314N>G

p.Glu105Gly

p.E105G

Q96SN8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0BV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

CDK5RAP2

SNV

Missense_Mutation

c.5248N>A

p.Glu1750Lys

p.E1750K

Q96SN8

protein_coding

tolerated(0.15)

benign(0.033)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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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