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: TRIB1

Gene summary for TRIB1

Gene summary.

Gene information	Species	Human
	Gene symbol	TRIB1
	Gene ID	10221
	Gene name	tribbles pseudokinase 1
	Gene Alias	C8FW
	Cytomap	8q24.13
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q96RU8

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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
10221	TRIB1	sample1	Human	Cervix	CC	1.64e-05	4.31e-01	0.0959
10221	TRIB1	sample3	Human	Cervix	CC	4.25e-02	2.03e-01	0.1387
10221	TRIB1	T1	Human	Cervix	CC	3.33e-16	5.26e-01	0.0918
10221	TRIB1	T2	Human	Cervix	CC	4.86e-05	4.85e-01	0.0709
10221	TRIB1	LZE7T	Human	Esophagus	ESCC	1.72e-03	-1.87e-01	0.0667
10221	TRIB1	LZE24T	Human	Esophagus	ESCC	7.48e-04	7.30e-01	0.0596
10221	TRIB1	LZE6T	Human	Esophagus	ESCC	7.44e-06	-5.45e-01	0.0845
10221	TRIB1	P2T-E	Human	Esophagus	ESCC	5.20e-18	6.37e-01	0.1177
10221	TRIB1	P4T-E	Human	Esophagus	ESCC	2.93e-10	8.34e-01	0.1323
10221	TRIB1	P5T-E	Human	Esophagus	ESCC	8.42e-16	8.14e-01	0.1327
10221	TRIB1	P8T-E	Human	Esophagus	ESCC	1.09e-19	1.14e+00	0.0889
10221	TRIB1	P10T-E	Human	Esophagus	ESCC	4.06e-09	-4.35e-01	0.116
10221	TRIB1	P11T-E	Human	Esophagus	ESCC	3.29e-08	1.09e+00	0.1426
10221	TRIB1	P12T-E	Human	Esophagus	ESCC	1.55e-13	7.90e-01	0.1122
10221	TRIB1	P15T-E	Human	Esophagus	ESCC	1.47e-09	1.15e+00	0.1149
10221	TRIB1	P16T-E	Human	Esophagus	ESCC	6.52e-07	3.53e-01	0.1153
10221	TRIB1	P20T-E	Human	Esophagus	ESCC	7.22e-04	5.75e-01	0.1124
10221	TRIB1	P21T-E	Human	Esophagus	ESCC	9.45e-05	4.56e-01	0.1617
10221	TRIB1	P23T-E	Human	Esophagus	ESCC	2.17e-37	2.77e+00	0.108
10221	TRIB1	P26T-E	Human	Esophagus	ESCC	3.74e-48	1.68e+00	0.1276

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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
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:007190023	Oral cavity	EOLP	regulation of protein serine/threonine kinase activity	75/2218	359/18723	5.81e-07	1.53e-05	75
GO:190210514	Oral cavity	EOLP	regulation of leukocyte differentiation	62/2218	279/18723	6.18e-07	1.60e-05	62
GO:003300212	Oral cavity	EOLP	muscle cell proliferation	56/2218	248/18723	1.25e-06	3.00e-05	56
GO:004573226	Oral cavity	EOLP	positive regulation of protein catabolic process	53/2218	231/18723	1.43e-06	3.42e-05	53
GO:004865915	Oral cavity	EOLP	smooth muscle cell proliferation	44/2218	184/18723	3.47e-06	7.48e-05	44
GO:000257323	Oral cavity	EOLP	myeloid leukocyte differentiation	48/2218	208/18723	3.71e-06	7.88e-05	48
GO:006113626	Oral cavity	EOLP	regulation of proteasomal protein catabolic process	44/2218	187/18723	5.44e-06	1.08e-04	44
GO:190336426	Oral cavity	EOLP	positive regulation of cellular protein catabolic process	38/2218	155/18723	8.47e-06	1.61e-04	38
GO:004866015	Oral cavity	EOLP	regulation of smooth muscle cell proliferation	42/2218	180/18723	1.10e-05	1.93e-04	42
GO:000283221	Oral cavity	EOLP	negative regulation of response to biotic stimulus	28/2218	108/18723	4.29e-05	5.82e-04	28
GO:001072021	Oral cavity	EOLP	positive regulation of cell development	59/2218	298/18723	4.72e-05	6.25e-04	59
GO:005109021	Oral cavity	EOLP	regulation of DNA-binding transcription factor activity	80/2218	440/18723	5.77e-05	7.31e-04	80
GO:003249623	Oral cavity	EOLP	response to lipopolysaccharide	65/2218	343/18723	8.02e-05	9.65e-04	65
GO:004340521	Oral cavity	EOLP	regulation of MAP kinase activity	39/2218	177/18723	8.57e-05	1.02e-03	39
GO:200006024	Oral cavity	EOLP	positive regulation of ubiquitin-dependent protein catabolic process	27/2218	107/18723	9.64e-05	1.12e-03	27
GO:004563916	Oral cavity	EOLP	positive regulation of myeloid cell differentiation	26/2218	103/18723	1.28e-04	1.41e-03	26
GO:000223724	Oral cavity	EOLP	response to molecule of bacterial origin	67/2218	363/18723	1.42e-04	1.53e-03	67
GO:00303366	Oral cavity	EOLP	negative regulation of cell migration	64/2218	344/18723	1.57e-04	1.67e-03	64
GO:00321023	Oral cavity	EOLP	negative regulation of response to external stimulus	75/2218	420/18723	1.74e-04	1.80e-03	75
GO:003109824	Oral cavity	EOLP	stress-activated protein kinase signaling cascade	49/2218	247/18723	1.89e-04	1.94e-03	49

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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

TRIB1

SNV

Missense_Mutation

c.616N>G

p.Leu206Val

p.L206V

Q96RU8

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TRIB1

SNV

Missense_Mutation

c.1015N>A

p.Glu339Lys

p.E339K

Q96RU8

protein_coding

tolerated(0.45)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIB1

SNV

Missense_Mutation

rs138022510

c.947G>A

p.Arg316His

p.R316H

Q96RU8

protein_coding

deleterious(0.03)

probably_damaging(0.986)

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

TRIB1

SNV

Missense_Mutation

c.424N>C

p.Asn142His

p.N142H

Q96RU8

protein_coding

tolerated(0.53)

benign(0.115)

TCGA-B6-A0RS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TRIB1

insertion

Frame_Shift_Ins

novel

c.565_566insACCC

p.Ile189AsnfsTer22

p.I189Nfs*22

Q96RU8

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TRIB1

insertion

Nonsense_Mutation

novel

c.566_567insTTGGGTATTTGCAAGTCTAGAGCTTTAGG

p.Val190TrpfsTer9

p.V190Wfs*9

Q96RU8

protein_coding

TCGA-AN-A04A-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TRIB1

insertion

Frame_Shift_Ins

novel

c.742_743insCTTGTAAGCTCCAGCATTATGAATACTATTTGGGGCTTTGCCTC

p.Tyr248SerfsTer17

p.Y248Sfs*17

Q96RU8

protein_coding

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

TRIB1

insertion

Frame_Shift_Ins

novel

c.507dupC

p.Tyr170LeufsTer40

p.Y170Lfs*40

Q96RU8

protein_coding

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TRIB1

SNV

Missense_Mutation

novel

c.974N>G

p.Glu325Gly

p.E325G

Q96RU8

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-ZJ-AB0I-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TRIB1

SNV

Missense_Mutation

rs776955393

c.1039A>G

p.Ile347Val

p.I347V

Q96RU8

protein_coding

tolerated(0.54)

benign(0)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

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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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