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: MALT1

Gene summary for MALT1

Gene summary.

Gene information	Species	Human
	Gene symbol	MALT1
	Gene ID	10892
	Gene name	MALT1 paracaspase
	Gene Alias	IMD12
	Cytomap	18q21.32
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	A8K5S1

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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
10892	MALT1	LZE7T	Human	Esophagus	ESCC	1.02e-06	3.46e-01	0.0667
10892	MALT1	LZE20T	Human	Esophagus	ESCC	2.04e-03	7.47e-03	0.0662
10892	MALT1	LZE24T	Human	Esophagus	ESCC	6.45e-06	3.90e-02	0.0596
10892	MALT1	LZE21T	Human	Esophagus	ESCC	3.17e-02	3.64e-02	0.0655
10892	MALT1	P1T-E	Human	Esophagus	ESCC	1.46e-04	1.32e-01	0.0875
10892	MALT1	P2T-E	Human	Esophagus	ESCC	3.19e-40	6.66e-01	0.1177
10892	MALT1	P4T-E	Human	Esophagus	ESCC	2.61e-20	3.99e-01	0.1323
10892	MALT1	P5T-E	Human	Esophagus	ESCC	6.70e-24	1.74e-01	0.1327
10892	MALT1	P8T-E	Human	Esophagus	ESCC	1.94e-16	9.47e-02	0.0889
10892	MALT1	P9T-E	Human	Esophagus	ESCC	1.85e-09	5.62e-02	0.1131
10892	MALT1	P10T-E	Human	Esophagus	ESCC	4.14e-12	1.76e-02	0.116
10892	MALT1	P11T-E	Human	Esophagus	ESCC	2.70e-06	1.62e-01	0.1426
10892	MALT1	P12T-E	Human	Esophagus	ESCC	4.84e-10	3.16e-02	0.1122
10892	MALT1	P15T-E	Human	Esophagus	ESCC	2.38e-10	-1.12e-02	0.1149
10892	MALT1	P16T-E	Human	Esophagus	ESCC	2.62e-09	2.77e-02	0.1153
10892	MALT1	P20T-E	Human	Esophagus	ESCC	8.07e-13	1.10e-01	0.1124
10892	MALT1	P21T-E	Human	Esophagus	ESCC	1.40e-10	5.41e-02	0.1617
10892	MALT1	P22T-E	Human	Esophagus	ESCC	1.61e-15	5.20e-02	0.1236
10892	MALT1	P23T-E	Human	Esophagus	ESCC	4.19e-16	1.84e-01	0.108
10892	MALT1	P24T-E	Human	Esophagus	ESCC	1.52e-12	3.31e-02	0.1287

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ

∗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:0006913110	Esophagus	ESCC	nucleocytoplasmic transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:0051169110	Esophagus	ESCC	nuclear transport	230/8552	301/18723	6.04e-28	2.02e-25	230
GO:1903320111	Esophagus	ESCC	regulation of protein modification by small protein conjugation or removal	181/8552	242/18723	1.80e-20	2.60e-18	181
GO:0051168110	Esophagus	ESCC	nuclear export	126/8552	154/18723	1.88e-20	2.65e-18	126
GO:0045862111	Esophagus	ESCC	positive regulation of proteolysis	256/8552	372/18723	7.88e-20	9.43e-18	256
GO:0031396111	Esophagus	ESCC	regulation of protein ubiquitination	154/8552	210/18723	2.70e-16	2.04e-14	154
GO:004312318	Esophagus	ESCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	132/8552	186/18723	2.07e-12	8.58e-11	132
GO:0043122110	Esophagus	ESCC	regulation of I-kappaB kinase/NF-kappaB signaling	167/8552	249/18723	6.11e-12	2.32e-10	167
GO:2000116111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity	158/8552	235/18723	1.67e-11	5.90e-10	158
GO:0043281111	Esophagus	ESCC	regulation of cysteine-type endopeptidase activity involved in apoptotic process	143/8552	209/18723	2.12e-11	7.31e-10	143
GO:000724919	Esophagus	ESCC	I-kappaB kinase/NF-kappaB signaling	183/8552	281/18723	3.02e-11	1.01e-09	183
GO:0010952111	Esophagus	ESCC	positive regulation of peptidase activity	133/8552	197/18723	4.31e-10	1.14e-08	133
GO:190332216	Esophagus	ESCC	positive regulation of protein modification by small protein conjugation or removal	99/8552	138/18723	4.39e-10	1.16e-08	99
GO:0052547111	Esophagus	ESCC	regulation of peptidase activity	275/8552	461/18723	7.54e-10	1.88e-08	275
GO:0052548111	Esophagus	ESCC	regulation of endopeptidase activity	253/8552	432/18723	3.68e-08	6.78e-07	253
GO:004578527	Esophagus	ESCC	positive regulation of cell adhesion	255/8552	437/18723	5.07e-08	9.11e-07	255
GO:0010950111	Esophagus	ESCC	positive regulation of endopeptidase activity	116/8552	179/18723	1.77e-07	2.79e-06	116
GO:003139816	Esophagus	ESCC	positive regulation of protein ubiquitination	82/8552	119/18723	2.41e-07	3.64e-06	82
GO:00510908	Esophagus	ESCC	regulation of DNA-binding transcription factor activity	252/8552	440/18723	5.22e-07	6.97e-06	252
GO:00510918	Esophagus	ESCC	positive regulation of DNA-binding transcription factor activity	155/8552	260/18723	3.83e-06	4.14e-05	155

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05131211	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa051527	Esophagus	ESCC	Tuberculosis	111/4205	180/8465	7.14e-04	2.32e-03	1.19e-03	111
hsa040645	Esophagus	ESCC	NF-kappa B signaling pathway	67/4205	104/8465	1.62e-03	4.89e-03	2.50e-03	67
hsa046607	Esophagus	ESCC	T cell receptor signaling pathway	63/4205	104/8465	1.60e-02	3.60e-02	1.84e-02	63
hsa05131310	Esophagus	ESCC	Shigellosis	176/4205	247/8465	2.27e-12	4.01e-11	2.05e-11	176
hsa0462513	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa0515212	Esophagus	ESCC	Tuberculosis	111/4205	180/8465	7.14e-04	2.32e-03	1.19e-03	111
hsa0406412	Esophagus	ESCC	NF-kappa B signaling pathway	67/4205	104/8465	1.62e-03	4.89e-03	2.50e-03	67
hsa0466013	Esophagus	ESCC	T cell receptor signaling pathway	63/4205	104/8465	1.60e-02	3.60e-02	1.84e-02	63
hsa0513114	Liver	NAFLD	Shigellosis	48/1043	247/8465	7.82e-04	1.17e-02	9.39e-03	48
hsa0513115	Liver	NAFLD	Shigellosis	48/1043	247/8465	7.82e-04	1.17e-02	9.39e-03	48
hsa0513142	Liver	HCC	Shigellosis	150/4020	247/8465	1.53e-05	1.04e-04	5.81e-05	150
hsa0513152	Liver	HCC	Shigellosis	150/4020	247/8465	1.53e-05	1.04e-04	5.81e-05	150
hsa0513116	Lung	IAC	Shigellosis	58/1053	247/8465	8.21e-07	3.81e-05	2.53e-05	58
hsa04625	Lung	IAC	C-type lectin receptor signaling pathway	26/1053	104/8465	3.15e-04	3.11e-03	2.06e-03	26
hsa04660	Lung	IAC	T cell receptor signaling pathway	23/1053	104/8465	3.88e-03	1.88e-02	1.25e-02	23
hsa0513117	Lung	IAC	Shigellosis	58/1053	247/8465	8.21e-07	3.81e-05	2.53e-05	58
hsa046251	Lung	IAC	C-type lectin receptor signaling pathway	26/1053	104/8465	3.15e-04	3.11e-03	2.06e-03	26
hsa046601	Lung	IAC	T cell receptor signaling pathway	23/1053	104/8465	3.88e-03	1.88e-02	1.25e-02	23

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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

MALT1

SNV

Missense_Mutation

novel

c.1924G>A

p.Asp642Asn

p.D642N

Q9UDY8

protein_coding

deleterious(0.02)

probably_damaging(0.911)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MALT1

SNV

Missense_Mutation

novel

c.894N>A

p.Ser298Arg

p.S298R

Q9UDY8

protein_coding

tolerated(0.54)

benign(0.015)

TCGA-A7-A3IZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MALT1

SNV

Missense_Mutation

c.1364G>C

p.Gly455Ala

p.G455A

Q9UDY8

protein_coding

tolerated(0.12)

probably_damaging(0.989)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MALT1

SNV

Missense_Mutation

novel

c.1913N>G

p.Asp638Gly

p.D638G

Q9UDY8

protein_coding

tolerated(0.1)

benign(0.145)

TCGA-OL-A6VQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MALT1

insertion

Frame_Shift_Ins

novel

c.2285_2286insCAGAATTGAGAATTCCTATTATAACCATAGATTGTTGTTTTCATTG

p.Ser763ArgfsTer20

p.S763Rfs*20

Q9UDY8

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

MALT1

insertion

In_Frame_Ins

novel

c.2471_2472insTACTTGGTATCAAAGGATCTTCCCAAGCATTGCCTCTAT

p.Lys824delinsAsnThrTrpTyrGlnArgIlePheProSerIleAlaSerIle

p.K824delinsNTWYQRIFPSIASI

Q9UDY8

protein_coding

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MALT1

insertion

Nonsense_Mutation

novel

c.1324_1325insGAAGTTCAGACTGA

p.Val442GlyfsTer5

p.V442Gfs*5

Q9UDY8

protein_coding

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MALT1

insertion

Frame_Shift_Ins

novel

c.1326_1327insTTTTTGTTGTTTTTTACAGC

p.Gln443PhefsTer11

p.Q443Ffs*11

Q9UDY8

protein_coding

TCGA-B6-A0RE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MALT1

SNV

Missense_Mutation

rs780898848

c.1175N>A

p.Arg392His

p.R392H

Q9UDY8

protein_coding

tolerated(0.17)

benign(0.031)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MALT1

SNV

Missense_Mutation

c.1423C>G

p.Pro475Ala

p.P475A

Q9UDY8

protein_coding

tolerated(0.23)

benign(0.217)

TCGA-LP-A4AV-01

Cervix

cervical & endocervical cancer

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
10892	MALT1	ENZYME, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, PROTEASE	inhibitor	354702255	MEPAZINE

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