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: DNAJC15

Gene summary for DNAJC15

Gene summary.

Gene information	Species	Human
	Gene symbol	DNAJC15
	Gene ID	29103
	Gene name	DnaJ heat shock protein family (Hsp40) member C15
	Gene Alias	DNAJD1
	Cytomap	13q14.11
	Gene Type	protein-coding
	GO ID	GO:0002082
	UniProtAcc	Q9Y5T4

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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
29103	DNAJC15	CA_HPV_1	Human	Cervix	CC	1.07e-05	-1.77e-01	0.0264
29103	DNAJC15	CA_HPV_2	Human	Cervix	CC	1.36e-03	-3.14e-01	0.0391
29103	DNAJC15	CA_HPV_3	Human	Cervix	CC	1.30e-02	-2.83e-01	0.0414
29103	DNAJC15	N_HPV_1	Human	Cervix	N_HPV	1.21e-02	-1.94e-01	0.0079
29103	DNAJC15	CCI_1	Human	Cervix	CC	7.41e-10	-1.73e-02	0.528
29103	DNAJC15	CCI_3	Human	Cervix	CC	6.01e-09	-6.12e-01	0.516
29103	DNAJC15	CCII_1	Human	Cervix	CC	8.62e-11	-5.87e-01	0.3249
29103	DNAJC15	Tumor	Human	Cervix	CC	1.14e-39	-6.40e-01	0.1241
29103	DNAJC15	sample1	Human	Cervix	CC	2.93e-12	-6.31e-01	0.0959
29103	DNAJC15	sample3	Human	Cervix	CC	2.00e-33	-6.33e-01	0.1387
29103	DNAJC15	L1	Human	Cervix	CC	4.76e-09	-5.19e-01	0.0802
29103	DNAJC15	T1	Human	Cervix	CC	2.69e-24	-6.14e-01	0.0918
29103	DNAJC15	T3	Human	Cervix	CC	5.34e-36	-6.33e-01	0.1389
29103	DNAJC15	HTA11_99999965104_69814	Human	Colorectum	MSS	3.48e-03	4.40e-01	0.281
29103	DNAJC15	HTA11_99999973899_84307	Human	Colorectum	MSS	2.16e-10	9.15e-01	0.2585
29103	DNAJC15	F007	Human	Colorectum	FAP	2.78e-04	4.59e-01	0.1176
29103	DNAJC15	A015-C-203	Human	Colorectum	FAP	1.58e-15	-4.38e-02	-0.1294
29103	DNAJC15	A002-C-201	Human	Colorectum	FAP	3.83e-04	-5.90e-02	0.0324
29103	DNAJC15	A001-C-108	Human	Colorectum	FAP	5.83e-08	-4.47e-02	-0.0272
29103	DNAJC15	A002-C-205	Human	Colorectum	FAP	4.98e-09	-4.59e-02	-0.1236

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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
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:004603410	Cervix	CC	ATP metabolic process	90/2311	277/18723	7.90e-19	2.36e-15	90
GO:000611910	Cervix	CC	oxidative phosphorylation	55/2311	141/18723	7.12e-16	1.42e-12	55
GO:00090609	Cervix	CC	aerobic respiration	60/2311	189/18723	1.59e-12	6.36e-10	60
GO:00427739	Cervix	CC	ATP synthesis coupled electron transport	38/2311	95/18723	8.45e-12	2.66e-09	38
GO:00427759	Cervix	CC	mitochondrial ATP synthesis coupled electron transport	38/2311	95/18723	8.45e-12	2.66e-09	38
GO:00196469	Cervix	CC	aerobic electron transport chain	36/2311	87/18723	9.15e-12	2.74e-09	36
GO:00229049	Cervix	CC	respiratory electron transport chain	42/2311	114/18723	1.67e-11	4.77e-09	42
GO:00453339	Cervix	CC	cellular respiration	66/2311	230/18723	2.07e-11	5.39e-09	66
GO:00725949	Cervix	CC	establishment of protein localization to organelle	99/2311	422/18723	1.23e-10	2.11e-08	99
GO:00229009	Cervix	CC	electron transport chain	53/2311	175/18723	2.23e-10	3.43e-08	53
GO:007149610	Cervix	CC	cellular response to external stimulus	78/2311	320/18723	1.82e-09	1.98e-07	78
GO:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:00060919	Cervix	CC	generation of precursor metabolites and energy	105/2311	490/18723	7.40e-09	6.61e-07	105
GO:00159809	Cervix	CC	energy derivation by oxidation of organic compounds	74/2311	318/18723	3.83e-08	2.53e-06	74
GO:00061209	Cervix	CC	mitochondrial electron transport, NADH to ubiquinone	22/2311	51/18723	4.01e-08	2.54e-06	22
GO:00316689	Cervix	CC	cellular response to extracellular stimulus	59/2311	246/18723	3.03e-07	1.24e-05	59
GO:00068399	Cervix	CC	mitochondrial transport	60/2311	254/18723	4.21e-07	1.67e-05	60
GO:000660510	Cervix	CC	protein targeting	68/2311	314/18723	2.17e-06	6.55e-05	68
GO:003166710	Cervix	CC	response to nutrient levels	92/2311	474/18723	5.80e-06	1.42e-04	92
GO:00170388	Cervix	CC	protein import	48/2311	206/18723	8.62e-06	1.98e-04	48

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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

DNAJC15

SNV

Missense_Mutation

novel

c.22G>T

p.Ala8Ser

p.A8S

Q9Y5T4

protein_coding

tolerated_low_confidence(0.24)

benign(0.049)

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DNAJC15

SNV

Missense_Mutation

rs756868611

c.68C>T

p.Ser23Leu

p.S23L

Q9Y5T4

protein_coding

deleterious_low_confidence(0.03)

benign(0.017)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

DNAJC15

SNV

Missense_Mutation

c.43C>T

p.Arg15Cys

p.R15C

Q9Y5T4

protein_coding

deleterious_low_confidence(0.04)

probably_damaging(0.997)

TCGA-AD-6895-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

DNAJC15

SNV

Missense_Mutation

novel

c.269N>C

p.Gln90Pro

p.Q90P

Q9Y5T4

protein_coding

tolerated(0.69)

benign(0.011)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

DNAJC15

SNV

Missense_Mutation

novel

c.215N>T

p.Ala72Val

p.A72V

Q9Y5T4

protein_coding

tolerated(0.56)

benign(0.003)

TCGA-AX-A3G8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

DNAJC15

SNV

Missense_Mutation

rs115803506

c.284N>A

p.Arg95Gln

p.R95Q

Q9Y5T4

protein_coding

tolerated(0.09)

probably_damaging(0.98)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

DNAJC15

SNV

Missense_Mutation

c.450T>G

p.His150Gln

p.H150Q

Q9Y5T4

protein_coding

tolerated_low_confidence(0.19)

benign(0.007)

TCGA-BS-A0TC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

DNAJC15

SNV

Missense_Mutation

c.369N>G

p.Asn123Lys

p.N123K

Q9Y5T4

protein_coding

deleterious(0)

probably_damaging(0.951)

TCGA-BS-A0UM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

DNAJC15

SNV

Missense_Mutation

rs765899911

c.163N>T

p.Arg55Cys

p.R55C

Q9Y5T4

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-D1-A175-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

DNAJC15

SNV

Missense_Mutation

rs760852761

c.407N>G

p.Lys136Arg

p.K136R

Q9Y5T4

protein_coding

deleterious(0.03)

probably_damaging(0.98)

TCGA-D1-A175-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

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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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