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: MSRB2

Gene summary for MSRB2

Gene summary.

Gene information	Species	Human
	Gene symbol	MSRB2
	Gene ID	22921
	Gene name	methionine sulfoxide reductase B2
	Gene Alias	CBS-1
	Cytomap	10p12.2
	Gene Type	protein-coding
	GO ID	GO:0006807
	UniProtAcc	Q9Y3D2

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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
22921	MSRB2	GSM4909281	Human	Breast	IDC	5.46e-06	3.55e-01	0.21
22921	MSRB2	GSM4909285	Human	Breast	IDC	1.52e-11	4.40e-01	0.21
22921	MSRB2	GSM4909289	Human	Breast	IDC	3.18e-04	5.20e-01	0.1064
22921	MSRB2	GSM4909293	Human	Breast	IDC	2.85e-12	4.19e-01	0.1581
22921	MSRB2	GSM4909294	Human	Breast	IDC	6.72e-03	3.28e-01	0.2022
22921	MSRB2	GSM4909296	Human	Breast	IDC	9.00e-04	2.68e-01	0.1524
22921	MSRB2	GSM4909301	Human	Breast	IDC	4.76e-11	4.72e-01	0.1577
22921	MSRB2	GSM4909304	Human	Breast	IDC	4.19e-07	4.29e-01	0.1636
22921	MSRB2	GSM4909306	Human	Breast	IDC	1.17e-02	3.49e-01	0.1564
22921	MSRB2	GSM4909308	Human	Breast	IDC	1.29e-07	2.86e-01	0.158
22921	MSRB2	GSM4909311	Human	Breast	IDC	8.76e-13	-6.77e-02	0.1534
22921	MSRB2	GSM4909315	Human	Breast	IDC	1.07e-17	7.08e-01	0.21
22921	MSRB2	GSM4909316	Human	Breast	IDC	1.92e-09	6.47e-01	0.21
22921	MSRB2	GSM4909319	Human	Breast	IDC	9.80e-21	9.84e-02	0.1563
22921	MSRB2	GSM4909321	Human	Breast	IDC	1.01e-02	7.41e-02	0.1559
22921	MSRB2	M1	Human	Breast	IDC	5.43e-04	2.84e-01	0.1577
22921	MSRB2	DCIS2	Human	Breast	DCIS	1.33e-51	2.29e-01	0.0085
22921	MSRB2	HTA11_1938_2000001011	Human	Colorectum	AD	1.25e-03	2.90e-01	-0.0811
22921	MSRB2	HTA11_347_2000001011	Human	Colorectum	AD	2.48e-08	2.68e-01	-0.1954
22921	MSRB2	HTA11_3361_2000001011	Human	Colorectum	AD	4.78e-03	2.48e-01	-0.1207

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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
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
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
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
GO:000697914	Breast	IDC	response to oxidative stress	83/1434	446/18723	2.36e-14	7.06e-12	83
GO:000701514	Breast	IDC	actin filament organization	55/1434	442/18723	2.45e-04	3.84e-03	55
GO:00512589	Breast	IDC	protein polymerization	38/1434	297/18723	1.26e-03	1.34e-02	38
GO:000697924	Breast	DCIS	response to oxidative stress	82/1390	446/18723	1.22e-14	3.85e-12	82
GO:000701524	Breast	DCIS	actin filament organization	56/1390	442/18723	5.90e-05	1.19e-03	56
GO:005125814	Breast	DCIS	protein polymerization	39/1390	297/18723	3.64e-04	5.15e-03	39
GO:0007015	Colorectum	AD	actin filament organization	167/3918	442/18723	1.65e-16	7.94e-14	167
GO:0008154	Colorectum	AD	actin polymerization or depolymerization	90/3918	218/18723	6.14e-12	8.23e-10	90
GO:0030041	Colorectum	AD	actin filament polymerization	81/3918	191/18723	1.35e-11	1.69e-09	81
GO:0051258	Colorectum	AD	protein polymerization	112/3918	297/18723	1.85e-11	2.27e-09	112
GO:0006979	Colorectum	AD	response to oxidative stress	145/3918	446/18723	5.16e-09	3.23e-07	145
GO:00070152	Colorectum	MSS	actin filament organization	146/3467	442/18723	1.16e-13	2.67e-11	146
GO:00081542	Colorectum	MSS	actin polymerization or depolymerization	79/3467	218/18723	4.14e-10	3.49e-08	79
GO:00300412	Colorectum	MSS	actin filament polymerization	71/3467	191/18723	8.77e-10	6.92e-08	71
GO:00512582	Colorectum	MSS	protein polymerization	97/3467	297/18723	2.98e-09	2.07e-07	97
GO:00069792	Colorectum	MSS	response to oxidative stress	128/3467	446/18723	7.65e-08	3.81e-06	128
GO:0006979111	Esophagus	ESCC	response to oxidative stress	303/8552	446/18723	7.15e-22	1.30e-19	303
GO:0051258111	Esophagus	ESCC	protein polymerization	183/8552	297/18723	1.94e-08	3.75e-07	183
GO:000701527	Esophagus	ESCC	actin filament organization	259/8552	442/18723	2.37e-08	4.50e-07	259
GO:000815420	Esophagus	ESCC	actin polymerization or depolymerization	130/8552	218/18723	2.19e-05	1.88e-04	130

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

MSRB2

deletion

Frame_Shift_Del

novel

c.350delA

p.His117LeufsTer14

p.H117Lfs*14

Q9Y3D2

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

MSRB2

SNV

Missense_Mutation

c.168N>T

p.Lys56Asn

p.K56N

Q9Y3D2

protein_coding

deleterious(0.03)

possibly_damaging(0.573)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

MSRB2

SNV

Missense_Mutation

novel

c.400N>A

p.Asp134Asn

p.D134N

Q9Y3D2

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-A5-A0G1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

MSRB2

SNV

Missense_Mutation

novel

c.280N>A

p.Asp94Asn

p.D94N

Q9Y3D2

protein_coding

tolerated(0.36)

benign(0.423)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

MSRB2

SNV

Missense_Mutation

c.122N>A

p.Ser41Tyr

p.S41Y

Q9Y3D2

protein_coding

deleterious(0.03)

benign(0.088)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

MSRB2

SNV

Missense_Mutation

c.168N>T

p.Lys56Asn

p.K56N

Q9Y3D2

protein_coding

deleterious(0.03)

possibly_damaging(0.573)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

MSRB2

SNV

Missense_Mutation

c.168N>T

p.Lys56Asn

p.K56N

Q9Y3D2

protein_coding

deleterious(0.03)

possibly_damaging(0.573)

TCGA-D1-A17Q-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MSRB2

SNV

Missense_Mutation

novel

c.274T>C

p.Cys92Arg

p.C92R

Q9Y3D2

protein_coding

deleterious(0)

probably_damaging(0.959)

TCGA-DI-A1BU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

MSRB2

SNV

Missense_Mutation

novel

c.335C>T

p.Ser112Leu

p.S112L

Q9Y3D2

protein_coding

deleterious(0.01)

probably_damaging(0.969)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

MSRB2

SNV

Missense_Mutation

c.122N>A

p.Ser41Tyr

p.S41Y

Q9Y3D2

protein_coding

deleterious(0.03)

benign(0.088)

TCGA-EO-A22U-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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