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: FKBP5

Gene summary for FKBP5

Gene summary.

Gene information	Species	Human
	Gene symbol	FKBP5
	Gene ID	2289
	Gene name	FKBP prolyl isomerase 5
	Gene Alias	AIG6
	Cytomap	6p21.31
	Gene Type	protein-coding
	GO ID	GO:0000413
	UniProtAcc	Q13451

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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
2289	FKBP5	GSM4909286	Human	Breast	IDC	3.51e-04	-1.54e-01	0.1081
2289	FKBP5	GSM4909293	Human	Breast	IDC	4.95e-03	1.07e-01	0.1581
2289	FKBP5	GSM4909302	Human	Breast	IDC	6.77e-21	6.25e-01	0.1545
2289	FKBP5	GSM4909303	Human	Breast	IDC	3.77e-04	4.60e-01	0.0438
2289	FKBP5	GSM4909304	Human	Breast	IDC	1.36e-12	4.10e-01	0.1636
2289	FKBP5	GSM4909311	Human	Breast	IDC	1.26e-03	-1.21e-01	0.1534
2289	FKBP5	GSM4909319	Human	Breast	IDC	2.75e-05	-9.06e-02	0.1563
2289	FKBP5	NCCBC11	Human	Breast	DCIS	3.08e-19	9.41e-01	0.1232
2289	FKBP5	NCCBC6	Human	Breast	DCIS	5.60e-06	6.57e-01	0.2095
2289	FKBP5	P1	Human	Breast	IDC	2.34e-02	-1.05e-01	0.1527
2289	FKBP5	DCIS2	Human	Breast	DCIS	6.04e-84	8.55e-01	0.0085
2289	FKBP5	CA_HPV_1	Human	Cervix	CC	4.43e-02	2.21e-01	0.0264
2289	FKBP5	N_HPV_2	Human	Cervix	N_HPV	3.17e-02	2.15e-01	-0.0131
2289	FKBP5	CCI_2	Human	Cervix	CC	8.83e-04	7.40e-01	0.5249
2289	FKBP5	CCI_3	Human	Cervix	CC	1.82e-03	7.30e-01	0.516
2289	FKBP5	HTA11_3410_2000001011	Human	Colorectum	AD	4.58e-52	-1.14e+00	0.0155
2289	FKBP5	HTA11_2487_2000001011	Human	Colorectum	SER	9.84e-14	-7.32e-01	-0.1808
2289	FKBP5	HTA11_2951_2000001011	Human	Colorectum	AD	7.45e-06	-9.79e-01	0.0216
2289	FKBP5	HTA11_1938_2000001011	Human	Colorectum	AD	5.24e-15	-9.15e-01	-0.0811
2289	FKBP5	HTA11_78_2000001011	Human	Colorectum	AD	1.31e-23	-8.70e-01	-0.1088

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:000645713	Breast	IDC	protein folding	47/1434	212/18723	2.31e-11	3.86e-09	47
GO:006107713	Breast	IDC	chaperone-mediated protein folding	21/1434	67/18723	1.35e-08	9.71e-07	21
GO:001820812	Breast	IDC	peptidyl-proline modification	13/1434	58/18723	3.59e-04	5.18e-03	13
GO:000645723	Breast	DCIS	protein folding	47/1390	212/18723	7.84e-12	1.53e-09	47
GO:006107722	Breast	DCIS	chaperone-mediated protein folding	21/1390	67/18723	7.81e-09	6.22e-07	21
GO:001820821	Breast	DCIS	peptidyl-proline modification	13/1390	58/18723	2.65e-04	4.03e-03	13
GO:00610779	Cervix	CC	chaperone-mediated protein folding	21/2311	67/18723	3.40e-05	5.55e-04	21
GO:00064579	Cervix	CC	protein folding	44/2311	212/18723	3.43e-04	3.59e-03	44
GO:000645724	Cervix	N_HPV	protein folding	22/534	212/18723	1.90e-07	1.57e-05	22
GO:006107723	Cervix	N_HPV	chaperone-mediated protein folding	12/534	67/18723	3.68e-07	2.54e-05	12
GO:0006457	Colorectum	AD	protein folding	73/3918	212/18723	3.24e-06	9.10e-05	73
GO:0061077	Colorectum	AD	chaperone-mediated protein folding	26/3918	67/18723	6.20e-04	6.48e-03	26
GO:00064571	Colorectum	SER	protein folding	54/2897	212/18723	1.04e-04	2.18e-03	54
GO:00610771	Colorectum	SER	chaperone-mediated protein folding	21/2897	67/18723	8.44e-04	1.04e-02	21
GO:00064572	Colorectum	MSS	protein folding	71/3467	212/18723	1.25e-07	5.91e-06	71
GO:00610772	Colorectum	MSS	chaperone-mediated protein folding	26/3467	67/18723	8.06e-05	1.33e-03	26
GO:00064574	Colorectum	FAP	protein folding	44/2622	212/18723	4.36e-03	2.98e-02	44
GO:000645710	Endometrium	AEH	protein folding	61/2100	212/18723	1.86e-12	3.48e-10	61
GO:006107710	Endometrium	AEH	chaperone-mediated protein folding	23/2100	67/18723	4.82e-07	1.94e-05	23
GO:00004133	Endometrium	AEH	protein peptidyl-prolyl isomerization	13/2100	42/18723	4.74e-04	4.91e-03	13

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0491523	Breast	IDC	Estrogen signaling pathway	35/867	138/8465	2.55e-07	5.18e-06	3.88e-06	35
hsa0491533	Breast	IDC	Estrogen signaling pathway	35/867	138/8465	2.55e-07	5.18e-06	3.88e-06	35
hsa0491542	Breast	DCIS	Estrogen signaling pathway	35/846	138/8465	1.40e-07	2.51e-06	1.85e-06	35
hsa0491552	Breast	DCIS	Estrogen signaling pathway	35/846	138/8465	1.40e-07	2.51e-06	1.85e-06	35
hsa0491520	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa04915110	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa0491543	Cervix	N_HPV	Estrogen signaling pathway	16/349	138/8465	1.68e-04	1.53e-03	1.19e-03	16
hsa0491553	Cervix	N_HPV	Estrogen signaling pathway	16/349	138/8465	1.68e-04	1.53e-03	1.19e-03	16
hsa04915	Colorectum	SER	Estrogen signaling pathway	38/1580	138/8465	6.51e-03	3.68e-02	2.67e-02	38
hsa049151	Colorectum	SER	Estrogen signaling pathway	38/1580	138/8465	6.51e-03	3.68e-02	2.67e-02	38
hsa049152	Colorectum	MSS	Estrogen signaling pathway	48/1875	138/8465	4.23e-04	3.08e-03	1.89e-03	48
hsa049153	Colorectum	MSS	Estrogen signaling pathway	48/1875	138/8465	4.23e-04	3.08e-03	1.89e-03	48
hsa049154	Colorectum	CRC	Estrogen signaling pathway	29/1091	138/8465	4.83e-03	2.66e-02	1.80e-02	29
hsa049155	Colorectum	CRC	Estrogen signaling pathway	29/1091	138/8465	4.83e-03	2.66e-02	1.80e-02	29
hsa0491525	Endometrium	AEH	Estrogen signaling pathway	35/1197	138/8465	3.10e-04	2.40e-03	1.75e-03	35
hsa04915111	Endometrium	AEH	Estrogen signaling pathway	35/1197	138/8465	3.10e-04	2.40e-03	1.75e-03	35
hsa0491514	Liver	Cyst	Estrogen signaling pathway	16/339	138/8465	1.20e-04	1.57e-03	1.30e-03	16
hsa0491515	Liver	Cyst	Estrogen signaling pathway	16/339	138/8465	1.20e-04	1.57e-03	1.30e-03	16
hsa0491529	Oral cavity	EOLP	Estrogen signaling pathway	38/1218	138/8465	3.78e-05	1.82e-04	1.07e-04	38
hsa04915113	Oral cavity	EOLP	Estrogen signaling pathway	38/1218	138/8465	3.78e-05	1.82e-04	1.07e-04	38

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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

FKBP5

SNV

Missense_Mutation

c.1303G>C

p.Glu435Gln

p.E435Q

Q13451

protein_coding

tolerated(0.11)

benign(0.007)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FKBP5

SNV

Missense_Mutation

c.728N>G

p.Tyr243Cys

p.Y243C

Q13451

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FKBP5

SNV

Missense_Mutation

novel

c.1142A>G

p.Asn381Ser

p.N381S

Q13451

protein_coding

tolerated(0.34)

possibly_damaging(0.685)

TCGA-B6-A402-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

FKBP5

insertion

Nonsense_Mutation

novel

c.24_25insTTAACCTCTCTGTGATTAAGTTCCTGTTTGTAAAATTAGAATAAT

p.Lys8_Asn9insLeuThrSerLeuTerLeuSerSerCysLeuTerAsnTerAsnAsn

p.K8_N9insLTSL*LSSCL*N*NN

Q13451

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

FKBP5

SNV

Missense_Mutation

rs200334349

c.119T>C

p.Val40Ala

p.V40A

Q13451

protein_coding

tolerated(0.34)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FKBP5

SNV

Missense_Mutation

c.391G>C

p.Glu131Gln

p.E131Q

Q13451

protein_coding

tolerated(0.06)

possibly_damaging(0.55)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

FKBP5

SNV

Missense_Mutation

rs759431987

c.1216N>T

p.Arg406Cys

p.R406C

Q13451

protein_coding

deleterious(0)

possibly_damaging(0.74)

TCGA-MA-AA3Y-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

FKBP5

SNV

Missense_Mutation

c.346N>A

p.Ala116Thr

p.A116T

Q13451

protein_coding

tolerated(0.15)

benign(0.003)

TCGA-AD-6889-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Chemotherapy

xeloda

FKBP5

SNV

Missense_Mutation

novel

c.366N>G

p.Ile122Met

p.I122M

Q13451

protein_coding

deleterious(0)

possibly_damaging(0.904)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

FKBP5

SNV

Missense_Mutation

novel

c.695A>C

p.Lys232Thr

p.K232T

Q13451

protein_coding

deleterious(0.04)

benign(0.081)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

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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
2289	FKBP5	DRUGGABLE GENOME		escitalopram	ESCITALOPRAM
2289	FKBP5	DRUGGABLE GENOME		gemcitabine	GEMCITABINE	23936393
2289	FKBP5	DRUGGABLE GENOME		citalopram	CITALOPRAM	18597649,21449676,20709156,19676097,15565110,23733030,17467808
2289	FKBP5	DRUGGABLE GENOME		clozapine	CLOZAPINE	25751398
2289	FKBP5	DRUGGABLE GENOME		paroxetine	PAROXETINE	18597649,21449676,20709156,19676097,15565110,23733030,17467808
2289	FKBP5	DRUGGABLE GENOME		corticosteroids		21788965
2289	FKBP5	DRUGGABLE GENOME		fluoxetine	FLUOXETINE	20709156,15565110
2289	FKBP5	DRUGGABLE GENOME		bupropion	BUPROPION	22947179
2289	FKBP5	DRUGGABLE GENOME		nefazodone	NEFAZODONE	18597649,21449676,20709156,19676097,15565110,23733030,17467808
2289	FKBP5	DRUGGABLE GENOME		antidepressants		18597649,21449676,20709156,19676097,15565110,23733030,17467808

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