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: MED13

Gene summary for MED13

Gene summary.

Gene information	Species	Human
	Gene symbol	MED13
	Gene ID	9969
	Gene name	mediator complex subunit 13
	Gene Alias	ARC250
	Cytomap	17q23.2
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	A0A024QZ75

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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
9969	MED13	GSM4909293	Human	Breast	IDC	1.35e-02	2.31e-01	0.1581
9969	MED13	GSM4909296	Human	Breast	IDC	6.77e-05	-1.69e-01	0.1524
9969	MED13	GSM4909311	Human	Breast	IDC	5.15e-08	-1.48e-01	0.1534
9969	MED13	GSM4909319	Human	Breast	IDC	1.13e-12	-1.63e-01	0.1563
9969	MED13	GSM4909321	Human	Breast	IDC	4.98e-02	-6.39e-02	0.1559
9969	MED13	M1	Human	Breast	IDC	1.79e-10	5.17e-01	0.1577
9969	MED13	NCCBC2	Human	Breast	DCIS	1.04e-04	6.20e-01	0.1554
9969	MED13	NCCBC5	Human	Breast	DCIS	5.37e-04	-1.83e-01	0.2046
9969	MED13	P1	Human	Breast	IDC	1.80e-06	3.27e-01	0.1527
9969	MED13	DCIS2	Human	Breast	DCIS	5.87e-51	2.67e-01	0.0085
9969	MED13	CCI_1	Human	Cervix	CC	1.54e-05	8.04e-01	0.528
9969	MED13	CCI_2	Human	Cervix	CC	5.79e-09	1.12e+00	0.5249
9969	MED13	CCI_3	Human	Cervix	CC	1.20e-09	1.01e+00	0.516
9969	MED13	HTA11_3410_2000001011	Human	Colorectum	AD	4.83e-14	-5.00e-01	0.0155
9969	MED13	HTA11_99999965062_69753	Human	Colorectum	MSI-H	4.85e-02	4.14e-01	0.3487
9969	MED13	A015-C-203	Human	Colorectum	FAP	1.27e-30	-3.03e-01	-0.1294
9969	MED13	A015-C-204	Human	Colorectum	FAP	1.73e-03	-1.18e-01	-0.0228
9969	MED13	A014-C-040	Human	Colorectum	FAP	5.03e-04	-3.90e-01	-0.1184
9969	MED13	A002-C-201	Human	Colorectum	FAP	3.72e-12	-2.78e-01	0.0324
9969	MED13	A002-C-203	Human	Colorectum	FAP	1.18e-02	-1.57e-01	0.2786

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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
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:00063523	Esophagus	HGIN	DNA-templated transcription, initiation	30/2587	130/18723	2.86e-03	2.79e-02	30
GO:20001424	Esophagus	HGIN	regulation of DNA-templated transcription, initiation	12/2587	40/18723	6.22e-03	4.95e-02	12
GO:00063673	Esophagus	ESCC	transcription initiation from RNA polymerase II promoter	56/8552	77/18723	1.30e-06	1.59e-05	56
GO:000635211	Esophagus	ESCC	DNA-templated transcription, initiation	86/8552	130/18723	1.88e-06	2.19e-05	86
GO:00602603	Esophagus	ESCC	regulation of transcription initiation from RNA polymerase II promoter	25/8552	33/18723	4.30e-04	2.43e-03	25
GO:200014212	Esophagus	ESCC	regulation of DNA-templated transcription, initiation	29/8552	40/18723	5.32e-04	2.93e-03	29
GO:20001443	Esophagus	ESCC	positive regulation of DNA-templated transcription, initiation	21/8552	31/18723	1.10e-02	3.70e-02	21
GO:0006367	Liver	Cirrhotic	transcription initiation from RNA polymerase II promoter	31/4634	77/18723	1.91e-03	1.20e-02	31
GO:0060260	Liver	Cirrhotic	regulation of transcription initiation from RNA polymerase II promoter	15/4634	33/18723	7.61e-03	3.60e-02	15
GO:2000142	Liver	Cirrhotic	regulation of DNA-templated transcription, initiation	17/4634	40/18723	1.04e-02	4.61e-02	17
GO:00063671	Liver	HCC	transcription initiation from RNA polymerase II promoter	52/7958	77/18723	7.87e-06	9.27e-05	52
GO:0006352	Liver	HCC	DNA-templated transcription, initiation	78/7958	130/18723	4.19e-05	4.11e-04	78
GO:20001421	Liver	HCC	regulation of DNA-templated transcription, initiation	28/7958	40/18723	4.01e-04	2.71e-03	28
GO:00602601	Liver	HCC	regulation of transcription initiation from RNA polymerase II promoter	24/7958	33/18723	4.24e-04	2.85e-03	24
GO:2000144	Liver	HCC	positive regulation of DNA-templated transcription, initiation	21/7958	31/18723	4.01e-03	1.76e-02	21
GO:0060261	Liver	HCC	positive regulation of transcription initiation from RNA polymerase II promoter	17/7958	25/18723	8.94e-03	3.45e-02	17
GO:00063522	Oral cavity	OSCC	DNA-templated transcription, initiation	74/7305	130/18723	2.56e-05	2.39e-04	74
GO:00063672	Oral cavity	OSCC	transcription initiation from RNA polymerase II promoter	46/7305	77/18723	1.82e-04	1.24e-03	46
GO:20001423	Oral cavity	OSCC	regulation of DNA-templated transcription, initiation	26/7305	40/18723	7.79e-04	4.23e-03	26
GO:20001442	Oral cavity	OSCC	positive regulation of DNA-templated transcription, initiation	21/7305	31/18723	1.13e-03	5.75e-03	21

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0491916	Breast	IDC	Thyroid hormone signaling pathway	23/867	121/8465	2.45e-03	1.69e-02	1.27e-02	23
hsa0491917	Breast	IDC	Thyroid hormone signaling pathway	23/867	121/8465	2.45e-03	1.69e-02	1.27e-02	23
hsa0491922	Breast	DCIS	Thyroid hormone signaling pathway	23/846	121/8465	1.78e-03	1.22e-02	9.00e-03	23
hsa0491932	Breast	DCIS	Thyroid hormone signaling pathway	23/846	121/8465	1.78e-03	1.22e-02	9.00e-03	23
hsa0491918	Cervix	CC	Thyroid hormone signaling pathway	33/1267	121/8465	3.11e-04	1.65e-03	9.78e-04	33
hsa0491919	Cervix	CC	Thyroid hormone signaling pathway	33/1267	121/8465	3.11e-04	1.65e-03	9.78e-04	33
hsa04919	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa049191	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa049196	Colorectum	MSI-H	Thyroid hormone signaling pathway	21/797	121/8465	4.18e-03	4.10e-02	3.44e-02	21
hsa049197	Colorectum	MSI-H	Thyroid hormone signaling pathway	21/797	121/8465	4.18e-03	4.10e-02	3.44e-02	21
hsa049198	Colorectum	FAP	Thyroid hormone signaling pathway	41/1404	121/8465	2.28e-06	4.28e-05	2.60e-05	41
hsa049199	Colorectum	FAP	Thyroid hormone signaling pathway	41/1404	121/8465	2.28e-06	4.28e-05	2.60e-05	41
hsa0491910	Colorectum	CRC	Thyroid hormone signaling pathway	35/1091	121/8465	2.05e-06	6.85e-05	4.64e-05	35
hsa0491911	Colorectum	CRC	Thyroid hormone signaling pathway	35/1091	121/8465	2.05e-06	6.85e-05	4.64e-05	35
hsa0491920	Endometrium	AEH	Thyroid hormone signaling pathway	30/1197	121/8465	1.20e-03	7.52e-03	5.50e-03	30
hsa04919110	Endometrium	AEH	Thyroid hormone signaling pathway	30/1197	121/8465	1.20e-03	7.52e-03	5.50e-03	30
hsa0491923	Endometrium	EEC	Thyroid hormone signaling pathway	29/1237	121/8465	4.08e-03	2.24e-02	1.67e-02	29
hsa0491933	Endometrium	EEC	Thyroid hormone signaling pathway	29/1237	121/8465	4.08e-03	2.24e-02	1.67e-02	29
hsa0491928	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa04919113	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78

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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

MED13

SNV

Missense_Mutation

novel

c.5458A>T

p.Ile1820Phe

p.I1820F

Q9UHV7

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-O2-A52Q-01

Lung

lung squamous cell carcinoma

Female

<65

III/IV

Unknown

MED13

deletion

Frame_Shift_Del

c.1101_1102delNN

p.Pro368GlnfsTer10

p.P368Qfs*10

Q9UHV7

protein_coding

TCGA-49-6744-01

Lung

lung adenocarcinoma

Female

<65

I/II

Chemotherapy

unknown

MED13

insertion

Nonsense_Mutation

novel

c.2392_2393insACATTTTAACATGA

p.Ser798TyrfsTer5

p.S798Yfs*5

Q9UHV7

protein_coding

TCGA-55-8507-01

Lung

lung adenocarcinoma

Male

<65

I/II

Unknown

MED13

insertion

In_Frame_Ins

novel

c.4457_4458insGAAGGTAGTTTA

p.Ser1486_Leu1487insLysValValTyr

p.S1486_L1487insKVVY

Q9UHV7

protein_coding

TCGA-62-A46V-01

Lung

lung adenocarcinoma

Female

>=65

I/II

Unknown

MED13

SNV

Missense_Mutation

novel

c.2935N>G

p.Gln979Glu

p.Q979E

Q9UHV7

protein_coding

deleterious(0.02)

probably_damaging(0.93)

TCGA-BA-4077-01

Oral cavity

head & neck squamous cell carcinoma

Female

<65

I/II

Chemotherapy

cetuximab

MED13

SNV

Missense_Mutation

novel

c.3844C>T

p.Leu1282Phe

p.L1282F

Q9UHV7

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-BA-5556-01

Oral cavity

head & neck squamous cell carcinoma

Female

<65

I/II

Unknown

MED13

SNV

Missense_Mutation

novel

c.4174C>T

p.Leu1392Phe

p.L1392F

Q9UHV7

protein_coding

deleterious(0.01)

probably_damaging(0.994)

TCGA-BB-A5HZ-01

Oral cavity

head & neck squamous cell carcinoma

Male

>=65

I/II

Unknown

MED13

SNV

Missense_Mutation

c.314G>A

p.Gly105Glu

p.G105E

Q9UHV7

protein_coding

deleterious(0)

possibly_damaging(0.852)

TCGA-CN-5360-01

Oral cavity

head & neck squamous cell carcinoma

Male

>=65

I/II

Chemotherapy

cisplatin

MED13

SNV

Missense_Mutation

novel

c.4064N>T

p.Trp1355Leu

p.W1355L

Q9UHV7

protein_coding

deleterious(0)

probably_damaging(0.986)

TCGA-CN-6010-01

Oral cavity

head & neck squamous cell carcinoma

Male

<65

I/II

Chemotherapy

cisplatin

MED13

SNV

Missense_Mutation

novel

c.605N>A

p.Ser202Asn

p.S202N

Q9UHV7

protein_coding

tolerated(0.11)

benign(0.011)

TCGA-CN-6988-01

Oral cavity

head & neck squamous cell carcinoma

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

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