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: MED13L

Gene summary for MED13L

Gene summary.

Gene information	Species	Human
	Gene symbol	MED13L
	Gene ID	23389
	Gene name	mediator complex subunit 13L
	Gene Alias	MRFACD
	Cytomap	12q24.21
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q71F56

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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
23389	MED13L	GSM4909282	Human	Breast	IDC	9.39e-03	-1.50e-01	-0.0288
23389	MED13L	GSM4909293	Human	Breast	IDC	1.20e-08	3.24e-01	0.1581
23389	MED13L	GSM4909304	Human	Breast	IDC	6.92e-08	3.44e-01	0.1636
23389	MED13L	GSM4909308	Human	Breast	IDC	1.85e-03	2.66e-01	0.158
23389	MED13L	GSM4909311	Human	Breast	IDC	2.84e-06	-2.06e-01	0.1534
23389	MED13L	GSM4909319	Human	Breast	IDC	2.42e-07	-1.46e-01	0.1563
23389	MED13L	GSM4909320	Human	Breast	IDC	6.27e-03	-2.23e-01	0.1575
23389	MED13L	GSM4909321	Human	Breast	IDC	3.66e-03	-1.26e-01	0.1559
23389	MED13L	NCCBC14	Human	Breast	DCIS	1.90e-02	-3.81e-02	0.2021
23389	MED13L	P1	Human	Breast	IDC	7.92e-04	1.56e-01	0.1527
23389	MED13L	P3	Human	Breast	IDC	1.14e-02	6.33e-01	0.1542
23389	MED13L	DCIS2	Human	Breast	DCIS	8.00e-78	5.02e-01	0.0085
23389	MED13L	CA_HPV_3	Human	Cervix	CC	2.45e-02	1.08e-01	0.0414
23389	MED13L	CCI_1	Human	Cervix	CC	3.31e-08	1.12e+00	0.528
23389	MED13L	CCI_2	Human	Cervix	CC	4.44e-15	2.12e+00	0.5249
23389	MED13L	CCI_3	Human	Cervix	CC	1.88e-19	1.73e+00	0.516
23389	MED13L	HTA11_3410_2000001011	Human	Colorectum	AD	4.01e-25	-6.87e-01	0.0155
23389	MED13L	HTA11_2951_2000001011	Human	Colorectum	AD	2.79e-03	-7.16e-01	0.0216
23389	MED13L	HTA11_3361_2000001011	Human	Colorectum	AD	1.35e-10	-6.57e-01	-0.1207
23389	MED13L	HTA11_5212_2000001011	Human	Colorectum	AD	2.76e-02	-4.35e-01	-0.2061

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
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

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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
hsa049192	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa049193	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa049194	Colorectum	MSS	Thyroid hormone signaling pathway	46/1875	121/8465	5.04e-05	4.97e-04	3.05e-04	46
hsa049195	Colorectum	MSS	Thyroid hormone signaling pathway	46/1875	121/8465	5.04e-05	4.97e-04	3.05e-04	46
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

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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

MED13L

SNV

Missense_Mutation

c.6008N>T

p.Ser2003Leu

p.S2003L

Q71F56

protein_coding

deleterious(0)

benign(0.138)

TCGA-A1-A0SH-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

MED13L

SNV

Missense_Mutation

rs563883392

c.83N>T

p.Thr28Met

p.T28M

Q71F56

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MED13L

SNV

Missense_Mutation

c.4558N>T

p.Asp1520Tyr

p.D1520Y

Q71F56

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MED13L

SNV

Missense_Mutation

novel

c.6427N>A

p.Glu2143Lys

p.E2143K

Q71F56

protein_coding

deleterious(0.01)

possibly_damaging(0.826)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MED13L

SNV

Missense_Mutation

novel

c.1441N>C

p.Lys481Gln

p.K481Q

Q71F56

protein_coding

deleterious(0.01)

probably_damaging(0.987)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MED13L

SNV

Missense_Mutation

novel

c.4709N>T

p.Ser1570Phe

p.S1570F

Q71F56

protein_coding

deleterious(0.03)

benign(0.136)

TCGA-D8-A73U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

MED13L

SNV

Missense_Mutation

c.3389N>A

p.Ser1130Asn

p.S1130N

Q71F56

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-E2-A15D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MED13L

SNV

Missense_Mutation

c.6415N>C

p.Ala2139Pro

p.A2139P

Q71F56

protein_coding

tolerated(0.13)

possibly_damaging(0.825)

TCGA-E2-A1B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Adriamycin

MED13L

SNV

Missense_Mutation

c.3343N>G

p.Leu1115Val

p.L1115V

Q71F56

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

MED13L

SNV

Missense_Mutation

novel

c.3133N>T

p.Arg1045Cys

p.R1045C

Q71F56

protein_coding

deleterious(0)

probably_damaging(0.94)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

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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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