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: TRAF5

Gene summary for TRAF5

Gene summary.

Gene information	Species	Human
	Gene symbol	TRAF5
	Gene ID	7188
	Gene name	TNF receptor associated factor 5
	Gene Alias	MGC:39780
	Cytomap	1q32.3
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	O00463

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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
7188	TRAF5	HTA11_99999970781_79442	Human	Colorectum	MSS	4.08e-02	3.76e-01	0.294
7188	TRAF5	HTA11_99999965104_69814	Human	Colorectum	MSS	6.08e-04	4.67e-01	0.281
7188	TRAF5	HTA11_99999971662_82457	Human	Colorectum	MSS	1.35e-08	6.71e-01	0.3859
7188	TRAF5	A002-C-010	Human	Colorectum	FAP	1.12e-03	3.72e-01	0.242
7188	TRAF5	A015-C-203	Human	Colorectum	FAP	1.00e-14	2.61e-01	-0.1294
7188	TRAF5	A002-C-201	Human	Colorectum	FAP	2.54e-07	3.42e-01	0.0324
7188	TRAF5	A001-C-108	Human	Colorectum	FAP	2.32e-07	3.64e-01	-0.0272
7188	TRAF5	A002-C-021	Human	Colorectum	FAP	8.51e-13	5.75e-01	0.1171
7188	TRAF5	A002-C-205	Human	Colorectum	FAP	2.70e-08	1.18e-01	-0.1236
7188	TRAF5	A001-C-104	Human	Colorectum	FAP	3.64e-07	4.42e-01	0.0184
7188	TRAF5	A015-C-005	Human	Colorectum	FAP	9.55e-03	3.79e-01	-0.0336
7188	TRAF5	A015-C-006	Human	Colorectum	FAP	5.99e-06	1.48e-01	-0.0994
7188	TRAF5	A015-C-106	Human	Colorectum	FAP	8.96e-06	3.78e-01	-0.0511
7188	TRAF5	A002-C-114	Human	Colorectum	FAP	1.97e-06	1.24e-01	-0.1561
7188	TRAF5	A015-C-104	Human	Colorectum	FAP	1.17e-15	2.83e-01	-0.1899
7188	TRAF5	A001-C-014	Human	Colorectum	FAP	2.48e-09	3.84e-01	0.0135
7188	TRAF5	A002-C-016	Human	Colorectum	FAP	6.60e-07	2.04e-01	0.0521
7188	TRAF5	A015-C-002	Human	Colorectum	FAP	4.84e-03	1.57e-01	-0.0763
7188	TRAF5	A001-C-203	Human	Colorectum	FAP	1.73e-03	2.65e-01	-0.0481
7188	TRAF5	A002-C-116	Human	Colorectum	FAP	1.73e-11	1.33e-02	-0.0452

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease

∗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:19033112	Colorectum	MSS	regulation of mRNA metabolic process	115/3467	288/18723	1.23e-17	6.41e-15	115
GO:00064012	Colorectum	MSS	RNA catabolic process	102/3467	278/18723	5.07e-13	1.02e-10	102
GO:00064022	Colorectum	MSS	mRNA catabolic process	89/3467	232/18723	8.70e-13	1.60e-10	89
GO:00313302	Colorectum	MSS	negative regulation of cellular catabolic process	96/3467	262/18723	2.67e-12	4.63e-10	96
GO:00098952	Colorectum	MSS	negative regulation of catabolic process	110/3467	320/18723	7.88e-12	1.20e-09	110
GO:00442702	Colorectum	MSS	cellular nitrogen compound catabolic process	141/3467	451/18723	2.95e-11	3.83e-09	141
GO:00467002	Colorectum	MSS	heterocycle catabolic process	139/3467	445/18723	4.37e-11	5.05e-09	139
GO:00346552	Colorectum	MSS	nucleobase-containing compound catabolic process	129/3467	407/18723	7.48e-11	8.18e-09	129
GO:00610132	Colorectum	MSS	regulation of mRNA catabolic process	66/3467	166/18723	1.25e-10	1.26e-08	66
GO:19013612	Colorectum	MSS	organic cyclic compound catabolic process	148/3467	495/18723	3.47e-10	3.18e-08	148
GO:00434872	Colorectum	MSS	regulation of RNA stability	66/3467	170/18723	4.14e-10	3.49e-08	66
GO:00434882	Colorectum	MSS	regulation of mRNA stability	62/3467	158/18723	8.41e-10	6.81e-08	62
GO:00194392	Colorectum	MSS	aromatic compound catabolic process	140/3467	467/18723	8.56e-10	6.85e-08	140
GO:19033122	Colorectum	MSS	negative regulation of mRNA metabolic process	37/3467	92/18723	1.00e-06	3.46e-05	37
GO:19023691	Colorectum	MSS	negative regulation of RNA catabolic process	32/3467	75/18723	1.14e-06	3.87e-05	32
GO:00002092	Colorectum	MSS	protein polyubiquitination	72/3467	236/18723	5.19e-06	1.42e-04	72
GO:00434891	Colorectum	MSS	RNA stabilization	26/3467	65/18723	4.39e-05	8.17e-04	26
GO:00431221	Colorectum	MSS	regulation of I-kappaB kinase/NF-kappaB signaling	71/3467	249/18723	7.12e-05	1.21e-03	71
GO:19023731	Colorectum	MSS	negative regulation of mRNA catabolic process	25/3467	63/18723	7.15e-05	1.21e-03	25
GO:00072491	Colorectum	MSS	I-kappaB kinase/NF-kappaB signaling	77/3467	281/18723	1.51e-04	2.19e-03	77

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa051314	Colorectum	MSS	Shigellosis	94/1875	247/8465	6.82e-09	1.34e-07	8.23e-08	94
hsa051634	Colorectum	MSS	Human cytomegalovirus infection	74/1875	225/8465	1.12e-04	1.01e-03	6.19e-04	74
hsa051704	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa05169	Colorectum	MSS	Epstein-Barr virus infection	63/1875	202/8465	1.63e-03	8.98e-03	5.50e-03	63
hsa05222	Colorectum	MSS	Small cell lung cancer	30/1875	92/8465	1.31e-02	4.30e-02	2.64e-02	30
hsa051315	Colorectum	MSS	Shigellosis	94/1875	247/8465	6.82e-09	1.34e-07	8.23e-08	94
hsa051635	Colorectum	MSS	Human cytomegalovirus infection	74/1875	225/8465	1.12e-04	1.01e-03	6.19e-04	74
hsa051705	Colorectum	MSS	Human immunodeficiency virus 1 infection	69/1875	212/8465	2.66e-04	1.98e-03	1.21e-03	69
hsa051691	Colorectum	MSS	Epstein-Barr virus infection	63/1875	202/8465	1.63e-03	8.98e-03	5.50e-03	63
hsa052221	Colorectum	MSS	Small cell lung cancer	30/1875	92/8465	1.31e-02	4.30e-02	2.64e-02	30
hsa051318	Colorectum	FAP	Shigellosis	76/1404	247/8465	1.57e-08	5.84e-07	3.55e-07	76
hsa051636	Colorectum	FAP	Human cytomegalovirus infection	55/1404	225/8465	1.42e-03	7.67e-03	4.67e-03	55
hsa051706	Colorectum	FAP	Human immunodeficiency virus 1 infection	51/1404	212/8465	2.98e-03	1.29e-02	7.87e-03	51
hsa052222	Colorectum	FAP	Small cell lung cancer	24/1404	92/8465	1.33e-02	4.46e-02	2.71e-02	24
hsa051319	Colorectum	FAP	Shigellosis	76/1404	247/8465	1.57e-08	5.84e-07	3.55e-07	76
hsa051637	Colorectum	FAP	Human cytomegalovirus infection	55/1404	225/8465	1.42e-03	7.67e-03	4.67e-03	55
hsa051707	Colorectum	FAP	Human immunodeficiency virus 1 infection	51/1404	212/8465	2.98e-03	1.29e-02	7.87e-03	51
hsa052223	Colorectum	FAP	Small cell lung cancer	24/1404	92/8465	1.33e-02	4.46e-02	2.71e-02	24
hsa051638	Colorectum	CRC	Human cytomegalovirus infection	45/1091	225/8465	1.54e-03	1.17e-02	7.94e-03	45
hsa051639	Colorectum	CRC	Human cytomegalovirus infection	45/1091	225/8465	1.54e-03	1.17e-02	7.94e-03	45

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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

TRAF5

SNV

Missense_Mutation

c.293N>A

p.Cys98Tyr

p.C98Y

O00463

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A2-A04N-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

TRAF5

SNV

Missense_Mutation

c.4G>C

p.Ala2Pro

p.A2P

O00463

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.99)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TRAF5

SNV

Missense_Mutation

novel

c.1615N>G

p.Lys539Glu

p.K539E

O00463

protein_coding

deleterious(0)

possibly_damaging(0.584)

TCGA-PL-A8LZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

TRAF5

insertion

Nonsense_Mutation

novel

c.273_274insTCTGTGTTGTAGTCACCCCAATCTTCCCTTGCCTTGAGGCA

p.Glu92SerfsTer4

p.E92Sfs*4

O00463

protein_coding

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TRAF5

insertion

Frame_Shift_Ins

novel

c.112_113insCTCCCACAATATGTGGGAATTCAAGAGGAGACTT

p.Arg38ProfsTer59

p.R38Pfs*59

O00463

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

TRAF5

deletion

Frame_Shift_Del

c.1348delN

p.Asp451MetfsTer32

p.D451Mfs*32

O00463

protein_coding

TCGA-E2-A15S-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

TRAF5

SNV

Missense_Mutation

c.1643C>T

p.Ala548Val

p.A548V

O00463

protein_coding

tolerated(1)

benign(0.005)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TRAF5

SNV

Missense_Mutation

novel

c.1579C>T

p.His527Tyr

p.H527Y

O00463

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-C5-A8XI-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

TRAF5

SNV

Missense_Mutation

c.1534N>C

p.Asp512His

p.D512H

O00463

protein_coding

tolerated(0.08)

probably_damaging(0.966)

TCGA-DS-A0VM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TRAF5

SNV

Missense_Mutation

rs113925874

c.695C>T

p.Thr232Met

p.T232M

O00463

protein_coding

tolerated(0.09)

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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