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:004217610	Cervix	CC	regulation of protein catabolic process	104/2311	391/18723	9.39e-15	9.36e-12	104
GO:004586210	Cervix	CC	positive regulation of proteolysis	95/2311	372/18723	1.84e-12	6.86e-10	95
GO:190336210	Cervix	CC	regulation of cellular protein catabolic process	72/2311	255/18723	5.98e-12	2.10e-09	72
GO:004573210	Cervix	CC	positive regulation of protein catabolic process	65/2311	231/18723	7.44e-11	1.39e-08	65
GO:001049810	Cervix	CC	proteasomal protein catabolic process	111/2311	490/18723	8.98e-11	1.58e-08	111
GO:000989610	Cervix	CC	positive regulation of catabolic process	109/2311	492/18723	5.26e-10	6.99e-08	109
GO:190305010	Cervix	CC	regulation of proteolysis involved in cellular protein catabolic process	60/2311	221/18723	1.82e-09	1.98e-07	60
GO:200005810	Cervix	CC	regulation of ubiquitin-dependent protein catabolic process	47/2311	164/18723	1.63e-08	1.25e-06	47
GO:004316110	Cervix	CC	proteasome-mediated ubiquitin-dependent protein catabolic process	91/2311	412/18723	1.65e-08	1.25e-06	91
GO:00026837	Cervix	CC	negative regulation of immune system process	94/2311	434/18723	2.63e-08	1.87e-06	94
GO:003133110	Cervix	CC	positive regulation of cellular catabolic process	91/2311	427/18723	9.64e-08	5.25e-06	91
GO:003009910	Cervix	CC	myeloid cell differentiation	83/2311	381/18723	1.31e-07	6.42e-06	83
GO:190336410	Cervix	CC	positive regulation of cellular protein catabolic process	43/2311	155/18723	1.80e-07	8.28e-06	43
GO:190370610	Cervix	CC	regulation of hemopoiesis	80/2311	367/18723	2.14e-07	9.55e-06	80
GO:006113610	Cervix	CC	regulation of proteasomal protein catabolic process	48/2311	187/18723	4.63e-07	1.77e-05	48
GO:003243410	Cervix	CC	regulation of proteasomal ubiquitin-dependent protein catabolic process	38/2311	134/18723	4.99e-07	1.88e-05	38
GO:00022379	Cervix	CC	response to molecule of bacterial origin	78/2311	363/18723	5.55e-07	2.06e-05	78
GO:00310988	Cervix	CC	stress-activated protein kinase signaling cascade	58/2311	247/18723	8.02e-07	2.89e-05	58
GO:00324969	Cervix	CC	response to lipopolysaccharide	74/2311	343/18723	9.15e-07	3.25e-05	74
GO:00719007	Cervix	CC	regulation of protein serine/threonine kinase activity	75/2311	359/18723	2.76e-06	8.02e-05	75

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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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