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:00071639	Cervix	CC	establishment or maintenance of cell polarity	63/2311	218/18723	4.25e-11	8.76e-09	63
GO:190290310	Cervix	CC	regulation of supramolecular fiber organization	92/2311	383/18723	1.49e-10	2.48e-08	92
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:00300108	Cervix	CC	establishment of cell polarity	42/2311	143/18723	4.30e-08	2.62e-06	42
GO:005125810	Cervix	CC	protein polymerization	70/2311	297/18723	5.20e-08	3.11e-06	70
GO:003227110	Cervix	CC	regulation of protein polymerization	57/2311	233/18723	2.37e-07	1.03e-05	57
GO:00447725	Cervix	CC	mitotic cell cycle phase transition	89/2311	424/18723	2.70e-07	1.12e-05	89
GO:003133410	Cervix	CC	positive regulation of protein-containing complex assembly	55/2311	237/18723	2.25e-06	6.73e-05	55
GO:190290510	Cervix	CC	positive regulation of supramolecular fiber organization	50/2311	209/18723	2.55e-06	7.54e-05	50
GO:00073466	Cervix	CC	regulation of mitotic cell cycle	88/2311	457/18723	1.26e-05	2.60e-04	88
GO:19019903	Cervix	CC	regulation of mitotic cell cycle phase transition	63/2311	299/18723	1.27e-05	2.60e-04	63
GO:005149510	Cervix	CC	positive regulation of cytoskeleton organization	50/2311	226/18723	2.53e-05	4.29e-04	50
GO:00516567	Cervix	CC	establishment of organelle localization	76/2311	390/18723	3.17e-05	5.21e-04	76
GO:00106399	Cervix	CC	negative regulation of organelle organization	68/2311	348/18723	7.40e-05	1.03e-03	68
GO:19019873	Cervix	CC	regulation of cell cycle phase transition	74/2311	390/18723	9.80e-05	1.27e-03	74
GO:003227310	Cervix	CC	positive regulation of protein polymerization	33/2311	138/18723	1.23e-04	1.53e-03	33
GO:00514948	Cervix	CC	negative regulation of cytoskeleton organization	37/2311	163/18723	1.57e-04	1.88e-03	37
GO:19021153	Cervix	CC	regulation of organelle assembly	40/2311	186/18723	2.92e-04	3.15e-03	40
GO:00705074	Cervix	CC	regulation of microtubule cytoskeleton organization	32/2311	148/18723	1.02e-03	8.51e-03	32
GO:00311134	Cervix	CC	regulation of microtubule polymerization	15/2311	55/18723	2.14e-03	1.54e-02	15

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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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