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: MIB1

Gene summary for MIB1

Gene summary.

Gene information	Species	Human
	Gene symbol	MIB1
	Gene ID	57534
	Gene name	MIB E3 ubiquitin protein ligase 1
	Gene Alias	DIP-1
	Cytomap	18q11.2
	Gene Type	protein-coding
	GO ID	GO:0001568
	UniProtAcc	Q86YT6

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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
57534	MIB1	CCI_1	Human	Cervix	CC	5.76e-04	7.41e-01	0.528
57534	MIB1	LZE2T	Human	Esophagus	ESCC	2.76e-02	3.26e-01	0.082
57534	MIB1	LZE4T	Human	Esophagus	ESCC	3.23e-05	1.03e-01	0.0811
57534	MIB1	LZE7T	Human	Esophagus	ESCC	2.63e-02	4.17e-01	0.0667
57534	MIB1	LZE22T	Human	Esophagus	ESCC	4.29e-02	2.19e-01	0.068
57534	MIB1	LZE24T	Human	Esophagus	ESCC	1.48e-07	2.28e-01	0.0596
57534	MIB1	P2T-E	Human	Esophagus	ESCC	2.31e-19	4.44e-01	0.1177
57534	MIB1	P4T-E	Human	Esophagus	ESCC	3.61e-14	2.80e-01	0.1323
57534	MIB1	P5T-E	Human	Esophagus	ESCC	8.02e-10	9.54e-02	0.1327
57534	MIB1	P8T-E	Human	Esophagus	ESCC	8.63e-10	2.42e-01	0.0889
57534	MIB1	P9T-E	Human	Esophagus	ESCC	3.85e-08	2.31e-01	0.1131
57534	MIB1	P10T-E	Human	Esophagus	ESCC	1.44e-13	2.42e-01	0.116
57534	MIB1	P11T-E	Human	Esophagus	ESCC	2.35e-06	2.05e-01	0.1426
57534	MIB1	P12T-E	Human	Esophagus	ESCC	1.09e-12	3.55e-01	0.1122
57534	MIB1	P15T-E	Human	Esophagus	ESCC	4.47e-10	1.90e-01	0.1149
57534	MIB1	P16T-E	Human	Esophagus	ESCC	7.18e-12	1.63e-01	0.1153
57534	MIB1	P17T-E	Human	Esophagus	ESCC	1.09e-04	8.49e-02	0.1278
57534	MIB1	P19T-E	Human	Esophagus	ESCC	2.15e-02	1.93e-01	0.1662
57534	MIB1	P20T-E	Human	Esophagus	ESCC	3.16e-02	2.52e-02	0.1124
57534	MIB1	P21T-E	Human	Esophagus	ESCC	7.42e-07	1.30e-01	0.1617

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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
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
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:00301008	Cervix	CC	regulation of endocytosis	47/2311	211/18723	3.65e-05	5.82e-04	47
GO:00458077	Cervix	CC	positive regulation of endocytosis	27/2311	100/18723	5.55e-05	8.10e-04	27
GO:00017018	Cervix	CC	in utero embryonic development	71/2311	367/18723	7.21e-05	1.00e-03	71
GO:00072194	Cervix	CC	Notch signaling pathway	39/2311	172/18723	1.08e-04	1.38e-03	39
GO:00351487	Cervix	CC	tube formation	31/2311	148/18723	2.07e-03	1.51e-02	31
GO:00018417	Cervix	CC	neural tube formation	23/2311	102/18723	2.80e-03	1.87e-02	23
GO:00605626	Cervix	CC	epithelial tube morphogenesis	57/2311	325/18723	3.79e-03	2.41e-02	57
GO:00219156	Cervix	CC	neural tube development	30/2311	152/18723	6.00e-03	3.43e-02	30
GO:0045665	Cervix	CC	negative regulation of neuron differentiation	16/2311	69/18723	8.75e-03	4.48e-02	16
GO:000170119	Esophagus	ESCC	in utero embryonic development	243/8552	367/18723	1.00e-15	6.86e-14	243
GO:000184115	Esophagus	ESCC	neural tube formation	75/8552	102/18723	9.68e-09	1.95e-07	75
GO:003010018	Esophagus	ESCC	regulation of endocytosis	135/8552	211/18723	5.75e-08	1.02e-06	135
GO:00219159	Esophagus	ESCC	neural tube development	101/8552	152/18723	1.78e-07	2.79e-06	101
GO:00163316	Esophagus	ESCC	morphogenesis of embryonic epithelium	98/8552	147/18723	2.12e-07	3.27e-06	98
GO:000183814	Esophagus	ESCC	embryonic epithelial tube formation	83/8552	121/18723	2.78e-07	4.08e-06	83
GO:003514815	Esophagus	ESCC	tube formation	96/8552	148/18723	1.86e-06	2.16e-05	96
GO:004580718	Esophagus	ESCC	positive regulation of endocytosis	69/8552	100/18723	1.97e-06	2.29e-05	69
GO:00721759	Esophagus	ESCC	epithelial tube formation	86/8552	132/18723	4.81e-06	5.10e-05	86
GO:006056210	Esophagus	ESCC	epithelial tube morphogenesis	187/8552	325/18723	9.95e-06	9.44e-05	187
GO:00072197	Esophagus	ESCC	Notch signaling pathway	106/8552	172/18723	1.74e-05	1.55e-04	106

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa05417110	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa05417310	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa0541722	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa0541732	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa0541742	Liver	HCC	Lipid and atherosclerosis	118/4020	215/8465	1.66e-02	3.92e-02	2.18e-02	118
hsa0541752	Liver	HCC	Lipid and atherosclerosis	118/4020	215/8465	1.66e-02	3.92e-02	2.18e-02	118
hsa0541728	Prostate	BPH	Lipid and atherosclerosis	66/1718	215/8465	1.68e-04	9.56e-04	5.92e-04	66
hsa05417112	Prostate	BPH	Lipid and atherosclerosis	66/1718	215/8465	1.68e-04	9.56e-04	5.92e-04	66
hsa0541729	Prostate	Tumor	Lipid and atherosclerosis	65/1791	215/8465	9.79e-04	4.44e-03	2.75e-03	65
hsa0541737	Prostate	Tumor	Lipid and atherosclerosis	65/1791	215/8465	9.79e-04	4.44e-03	2.75e-03	65

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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

MIB1

SNV

Missense_Mutation

c.435N>C

p.Lys145Asn

p.K145N

Q86YT6

protein_coding

deleterious(0.03)

possibly_damaging(0.775)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MIB1

SNV

Missense_Mutation

c.617G>A

p.Arg206Lys

p.R206K

Q86YT6

protein_coding

deleterious(0)

probably_damaging(0.92)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MIB1

SNV

Missense_Mutation

c.2119C>G

p.Leu707Val

p.L707V

Q86YT6

protein_coding

deleterious(0.02)

probably_damaging(0.92)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MIB1

SNV

Missense_Mutation

c.467N>C

p.Arg156Thr

p.R156T

Q86YT6

protein_coding

deleterious(0)

possibly_damaging(0.855)

TCGA-AO-A0JE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

MIB1

SNV

Missense_Mutation

c.2811N>G

p.Asp937Glu

p.D937E

Q86YT6

protein_coding

tolerated(0.43)

possibly_damaging(0.785)

TCGA-AO-A124-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MIB1

SNV

Missense_Mutation

c.923N>T

p.Pro308Leu

p.P308L

Q86YT6

protein_coding

deleterious(0)

probably_damaging(0.927)

TCGA-AR-A1AJ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MIB1

SNV

Missense_Mutation

c.2903A>G

p.Asp968Gly

p.D968G

Q86YT6

protein_coding

deleterious(0)

probably_damaging(0.959)

TCGA-AR-A24X-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MIB1

SNV

Missense_Mutation

c.1127N>G

p.Tyr376Cys

p.Y376C

Q86YT6

protein_coding

deleterious(0)

benign(0.431)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MIB1

SNV

Missense_Mutation

c.2382N>T

p.Lys794Asn

p.K794N

Q86YT6

protein_coding

tolerated(0.6)

benign(0.161)

TCGA-LL-A8F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

MIB1

insertion

Nonsense_Mutation

novel

c.2336_2337insTTAG

p.Cys780Ter

p.C780*

Q86YT6

protein_coding

TCGA-AN-A0FW-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

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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