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: MSI2

Gene summary for MSI2

Gene summary.

Gene information	Species	Human
	Gene symbol	MSI2
	Gene ID	124540
	Gene name	musashi RNA binding protein 2
	Gene Alias	MSI2H
	Cytomap	17q22
	Gene Type	protein-coding
	GO ID	GO:0008150
	UniProtAcc	B4DHE8

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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
124540	MSI2	GSM4909286	Human	Breast	IDC	2.40e-02	1.54e-01	0.1081
124540	MSI2	GSM4909293	Human	Breast	IDC	4.25e-09	2.63e-01	0.1581
124540	MSI2	GSM4909296	Human	Breast	IDC	8.04e-04	-1.22e-01	0.1524
124540	MSI2	GSM4909297	Human	Breast	IDC	3.51e-02	-7.67e-02	0.1517
124540	MSI2	GSM4909298	Human	Breast	IDC	1.31e-39	6.99e-01	0.1551
124540	MSI2	GSM4909304	Human	Breast	IDC	3.33e-45	8.35e-01	0.1636
124540	MSI2	GSM4909306	Human	Breast	IDC	2.14e-19	5.58e-01	0.1564
124540	MSI2	GSM4909307	Human	Breast	IDC	6.44e-11	4.39e-01	0.1569
124540	MSI2	GSM4909308	Human	Breast	IDC	3.61e-20	5.75e-01	0.158
124540	MSI2	GSM4909311	Human	Breast	IDC	9.29e-11	-9.33e-02	0.1534
124540	MSI2	GSM4909312	Human	Breast	IDC	1.87e-03	8.36e-02	0.1552
124540	MSI2	GSM4909319	Human	Breast	IDC	3.64e-15	-3.87e-02	0.1563
124540	MSI2	GSM4909321	Human	Breast	IDC	7.87e-05	-5.20e-02	0.1559
124540	MSI2	M1	Human	Breast	IDC	3.78e-30	9.15e-01	0.1577
124540	MSI2	NCCBC14	Human	Breast	DCIS	1.91e-03	3.44e-01	0.2021
124540	MSI2	P1	Human	Breast	IDC	4.53e-18	5.96e-01	0.1527
124540	MSI2	P2	Human	Breast	IDC	2.04e-05	5.30e-01	0.21
124540	MSI2	DCIS2	Human	Breast	DCIS	2.20e-53	1.98e-01	0.0085
124540	MSI2	CA_HPV_1	Human	Cervix	CC	2.76e-02	-1.57e-01	0.0264
124540	MSI2	CCI_1	Human	Cervix	CC	8.64e-07	9.41e-01	0.528

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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:00488634	Cervix	CC	stem cell differentiation	46/2311	206/18723	4.11e-05	6.36e-04	46
GO:0048863	Colorectum	FAP	stem cell differentiation	44/2622	206/18723	2.48e-03	1.96e-02	44
GO:00488631	Colorectum	CRC	stem cell differentiation	39/2078	206/18723	5.89e-04	7.89e-03	39
GO:00488635	Endometrium	AEH	stem cell differentiation	40/2100	206/18723	3.67e-04	3.99e-03	40
GO:004886314	Endometrium	EEC	stem cell differentiation	43/2168	206/18723	8.48e-05	1.21e-03	43
GO:00488638	Esophagus	ESCC	stem cell differentiation	122/8552	206/18723	5.95e-05	4.59e-04	122
GO:00488632	Liver	NAFLD	stem cell differentiation	33/1882	206/18723	4.81e-03	3.81e-02	33
GO:004886311	Liver	Cirrhotic	stem cell differentiation	66/4634	206/18723	1.06e-02	4.68e-02	66
GO:00488633	Lung	IAC	stem cell differentiation	38/2061	206/18723	9.79e-04	1.18e-02	38
GO:004886312	Lung	AIS	stem cell differentiation	39/1849	206/18723	5.25e-05	1.51e-03	39
GO:00488637	Oral cavity	OSCC	stem cell differentiation	96/7305	206/18723	1.55e-02	4.99e-02	96
GO:004886316	Oral cavity	NEOLP	stem cell differentiation	38/2005	206/18723	5.82e-04	5.05e-03	38
GO:00488636	Prostate	BPH	stem cell differentiation	55/3107	206/18723	1.56e-04	1.36e-03	55
GO:004886315	Prostate	Tumor	stem cell differentiation	55/3246	206/18723	4.81e-04	3.57e-03	55
GO:004886318	Thyroid	PTC	stem cell differentiation	85/5968	206/18723	2.71e-03	1.36e-02	85
GO:004886321	Thyroid	ATC	stem cell differentiation	97/6293	206/18723	3.88e-05	3.15e-04	97

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa03015	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030151	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301523	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa0301533	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa0301541	Oral cavity	EOLP	mRNA surveillance pathway	30/1218	97/8465	2.26e-05	1.20e-04	7.07e-05	30
hsa0301551	Oral cavity	EOLP	mRNA surveillance pathway	30/1218	97/8465	2.26e-05	1.20e-04	7.07e-05	30
hsa030156	Oral cavity	NEOLP	mRNA surveillance pathway	25/1112	97/8465	5.70e-04	3.18e-03	2.00e-03	25
hsa030157	Oral cavity	NEOLP	mRNA surveillance pathway	25/1112	97/8465	5.70e-04	3.18e-03	2.00e-03	25
hsa030155	Prostate	BPH	mRNA surveillance pathway	32/1718	97/8465	2.20e-03	8.63e-03	5.34e-03	32
hsa0301512	Prostate	BPH	mRNA surveillance pathway	32/1718	97/8465	2.20e-03	8.63e-03	5.34e-03	32
hsa0301522	Prostate	Tumor	mRNA surveillance pathway	33/1791	97/8465	2.18e-03	8.60e-03	5.33e-03	33
hsa0301532	Prostate	Tumor	mRNA surveillance pathway	33/1791	97/8465	2.18e-03	8.60e-03	5.33e-03	33

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
MSI2	VFIB	Colorectum	AD	MOB1B,AFF3,RCL1, etc.	3.27e-01
MSI2	VFIB	Colorectum	ADJ	MOB1B,AFF3,RCL1, etc.	1.80e-01
MSI2	VFIB	Colorectum	CRC	MOB1B,AFF3,RCL1, etc.	1.35e-01
MSI2	VFIB	Colorectum	FAP	MOB1B,AFF3,RCL1, etc.	3.41e-01
MSI2	VFIB	Colorectum	SER	MOB1B,AFF3,RCL1, etc.	2.88e-01
MSI2	CILIA	Endometrium	Healthy	SMKR1,CTSS,RPS6KA1, etc.	8.20e-02
MSI2	CD8TEREX	Pancreas	PanIN	PAM,SMYD3,NCALD, etc.	6.10e-02

∗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

MSI2

SNV

Missense_Mutation

c.475N>A

p.Glu159Lys

p.E159K

Q96DH6

protein_coding

deleterious(0.04)

benign(0.223)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MSI2

insertion

In_Frame_Ins

novel

c.986_987insGGAGAATGGAGATCTTTTTTGTCTTTTTTAAAAAAAAAAACA

p.Ter329delinsTrpGluAsnGlyAspLeuPheCysLeuPheTerLysLysLysGln

p.*329delinsWENGDLFCLF*KKKQ

Q96DH6

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

MSI2

SNV

Missense_Mutation

rs769598215

c.625N>A

p.Ala209Thr

p.A209T

Q96DH6

protein_coding

tolerated(0.12)

benign(0.109)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MSI2

SNV

Missense_Mutation

c.549N>C

p.Lys183Asn

p.K183N

Q96DH6

protein_coding

deleterious(0)

probably_damaging(0.987)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

MSI2

SNV

Missense_Mutation

rs772529843

c.767C>T

p.Ala256Val

p.A256V

Q96DH6

protein_coding

tolerated(0.06)

benign(0.436)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

MSI2

SNV

Missense_Mutation

novel

c.243N>T

p.Gln81His

p.Q81H

Q96DH6

protein_coding

deleterious(0.04)

benign(0.178)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MSI2

SNV

Missense_Mutation

novel

c.243N>T

p.Gln81His

p.Q81H

Q96DH6

protein_coding

deleterious(0.04)

benign(0.178)

TCGA-A5-A0GG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MSI2

SNV

Missense_Mutation

novel

c.944N>A

p.Ala315Asp

p.A315D

Q96DH6

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.448)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MSI2

SNV

Missense_Mutation

novel

c.902C>T

p.Ala301Val

p.A301V

Q96DH6

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

MSI2

SNV

Missense_Mutation

rs766409125

c.850N>A

p.Asp284Asn

p.D284N

Q96DH6

protein_coding

tolerated(0.11)

possibly_damaging(0.599)

TCGA-AX-A2HA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<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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