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: MID1

Gene summary for MID1

Gene summary.

Gene information	Species	Human
	Gene symbol	MID1
	Gene ID	4281
	Gene name	midline 1
	Gene Alias	BBBG1
	Cytomap	Xp22.2
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	A0A024RBV4

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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
4281	MID1	CA_HPV_3	Human	Cervix	CC	1.15e-03	7.83e-02	0.0414
4281	MID1	CCI_1	Human	Cervix	CC	1.21e-11	1.03e+00	0.528
4281	MID1	CCI_2	Human	Cervix	CC	5.49e-16	1.54e+00	0.5249
4281	MID1	CCII_1	Human	Cervix	CC	8.10e-03	2.34e-01	0.3249
4281	MID1	HTA11_1938_2000001011	Human	Colorectum	AD	8.38e-03	4.51e-01	-0.0811
4281	MID1	HTA11_347_2000001011	Human	Colorectum	AD	3.67e-16	8.05e-01	-0.1954
4281	MID1	HTA11_3361_2000001011	Human	Colorectum	AD	1.41e-04	-5.64e-01	-0.1207
4281	MID1	HTA11_5216_2000001011	Human	Colorectum	SER	6.28e-03	-4.30e-01	-0.1462
4281	MID1	HTA11_99999965104_69814	Human	Colorectum	MSS	1.51e-20	1.47e+00	0.281
4281	MID1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.98e-12	-5.14e-01	0.3005
4281	MID1	A015-C-203	Human	Colorectum	FAP	1.35e-30	-4.70e-01	-0.1294
4281	MID1	A015-C-204	Human	Colorectum	FAP	2.27e-03	-1.78e-01	-0.0228
4281	MID1	A014-C-040	Human	Colorectum	FAP	1.85e-04	-3.22e-01	-0.1184
4281	MID1	A002-C-201	Human	Colorectum	FAP	1.64e-10	-3.16e-01	0.0324
4281	MID1	A002-C-203	Human	Colorectum	FAP	1.21e-02	-1.45e-01	0.2786
4281	MID1	A001-C-119	Human	Colorectum	FAP	3.37e-06	-3.94e-01	-0.1557
4281	MID1	A001-C-108	Human	Colorectum	FAP	6.85e-18	-4.35e-01	-0.0272
4281	MID1	A002-C-205	Human	Colorectum	FAP	2.72e-25	-4.95e-01	-0.1236
4281	MID1	A001-C-104	Human	Colorectum	FAP	1.89e-02	-3.32e-01	0.0184
4281	MID1	A015-C-006	Human	Colorectum	FAP	2.84e-24	-8.23e-01	-0.0994

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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
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

∗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:00311093	Oral cavity	OSCC	microtubule polymerization or depolymerization	68/7305	122/18723	1.29e-04	9.21e-04	68
GO:00160537	Oral cavity	OSCC	organic acid biosynthetic process	155/7305	316/18723	1.64e-04	1.13e-03	155
GO:00463947	Oral cavity	OSCC	carboxylic acid biosynthetic process	154/7305	314/18723	1.73e-04	1.19e-03	154
GO:00066317	Oral cavity	OSCC	fatty acid metabolic process	186/7305	390/18723	2.65e-04	1.69e-03	186
GO:00432445	Oral cavity	OSCC	regulation of protein-containing complex disassembly	65/7305	121/18723	7.08e-04	3.90e-03	65
GO:00703045	Oral cavity	OSCC	positive regulation of stress-activated protein kinase signaling cascade	66/7305	128/18723	2.58e-03	1.13e-02	66
GO:00468906	Oral cavity	OSCC	regulation of lipid biosynthetic process	85/7305	171/18723	2.79e-03	1.21e-02	85
GO:00328863	Oral cavity	OSCC	regulation of microtubule-based process	115/7305	240/18723	2.95e-03	1.28e-02	115
GO:00192167	Oral cavity	OSCC	regulation of lipid metabolic process	154/7305	331/18723	3.00e-03	1.30e-02	154
GO:00620128	Oral cavity	OSCC	regulation of small molecule metabolic process	155/7305	334/18723	3.30e-03	1.41e-02	155
GO:00311103	Oral cavity	OSCC	regulation of microtubule polymerization or depolymerization	47/7305	88/18723	4.23e-03	1.72e-02	47
GO:00443803	Oral cavity	OSCC	protein localization to cytoskeleton	33/7305	58/18723	4.32e-03	1.75e-02	33
GO:00328744	Oral cavity	OSCC	positive regulation of stress-activated MAPK cascade	64/7305	126/18723	4.67e-03	1.87e-02	64
GO:00436244	Oral cavity	OSCC	cellular protein complex disassembly	68/7305	136/18723	5.84e-03	2.24e-02	68
GO:190290417	Oral cavity	OSCC	negative regulation of supramolecular fiber organization	81/7305	167/18723	7.70e-03	2.82e-02	81
GO:00434107	Oral cavity	OSCC	positive regulation of MAPK cascade	213/7305	480/18723	8.71e-03	3.16e-02	213
GO:00726984	Oral cavity	OSCC	protein localization to microtubule cytoskeleton	30/7305	54/18723	9.99e-03	3.49e-02	30
GO:0022411110	Oral cavity	LP	cellular component disassembly	173/4623	443/18723	9.97e-12	7.44e-10	173
GO:0051258110	Oral cavity	LP	protein polymerization	113/4623	297/18723	1.90e-07	5.92e-06	113
GO:001063919	Oral cavity	LP	negative regulation of organelle organization	127/4623	348/18723	5.07e-07	1.40e-05	127

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa0412016	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412017	Endometrium	AEH	Ubiquitin mediated proteolysis	41/1197	142/8465	3.42e-06	4.27e-05	3.13e-05	41
hsa0412023	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412033	Endometrium	EEC	Ubiquitin mediated proteolysis	41/1237	142/8465	7.86e-06	9.58e-05	7.14e-05	41
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122

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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

MID1

SNV

Missense_Mutation

c.427N>A

p.Asp143Asn

p.D143N

O15344

protein_coding

tolerated(0.22)

benign(0.025)

TCGA-A2-A0CL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

MID1

SNV

Missense_Mutation

c.265N>A

p.Ala89Thr

p.A89T

O15344

protein_coding

deleterious(0.01)

possibly_damaging(0.602)

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

MID1

SNV

Missense_Mutation

novel

c.1825N>A

p.Asp609Asn

p.D609N

O15344

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MID1

SNV

Missense_Mutation

rs150291968

c.1888G>A

p.Asp630Asn

p.D630N

O15344

protein_coding

tolerated(0.18)

benign(0.009)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MID1

SNV

Missense_Mutation

c.224N>A

p.Arg75His

p.R75H

O15344

protein_coding

deleterious(0)

probably_damaging(0.981)

TCGA-B6-A40B-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MID1

SNV

Missense_Mutation

rs765748631

c.203N>A

p.Arg68Gln

p.R68Q

O15344

protein_coding

deleterious(0.01)

benign(0.06)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MID1

SNV

Missense_Mutation

c.616N>A

p.Asp206Asn

p.D206N

O15344

protein_coding

tolerated(0.3)

benign(0.07)

TCGA-BH-A0C1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

MID1

SNV

Missense_Mutation

c.1082C>T

p.Thr361Ile

p.T361I

O15344

protein_coding

tolerated(0.05)

benign(0.093)

TCGA-E9-A1N9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MID1

SNV

Missense_Mutation

c.712N>C

p.Glu238Gln

p.E238Q

O15344

protein_coding

tolerated(0.24)

benign(0.146)

TCGA-E9-A1RG-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

MID1

SNV

Missense_Mutation

c.373N>A

p.Asp125Asn

p.D125N

O15344

protein_coding

deleterious(0.03)

benign(0.052)

TCGA-GM-A2DN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

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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
4281	MID1	ENZYME, B30_2 SPRY DOMAIN, DRUGGABLE GENOME		SUN-N8075

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