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: TRIP12

Gene summary for TRIP12

Gene summary.

Gene information	Species	Human
	Gene symbol	TRIP12
	Gene ID	9320
	Gene name	thyroid hormone receptor interactor 12
	Gene Alias	MRD49
	Cytomap	2q36.3
	Gene Type	protein-coding
	GO ID	GO:0000209
	UniProtAcc	Q14669

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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
9320	TRIP12	CA_HPV_1	Human	Cervix	CC	1.91e-02	4.30e-02	0.0264
9320	TRIP12	CCI_3	Human	Cervix	CC	9.20e-05	6.17e-01	0.516
9320	TRIP12	HTA11_3410_2000001011	Human	Colorectum	AD	3.16e-17	-5.64e-01	0.0155
9320	TRIP12	HTA11_3361_2000001011	Human	Colorectum	AD	1.90e-10	-5.95e-01	-0.1207
9320	TRIP12	HTA11_866_2000001011	Human	Colorectum	AD	1.89e-04	-3.52e-01	-0.1001
9320	TRIP12	HTA11_7862_2000001011	Human	Colorectum	AD	2.43e-02	-3.46e-01	-0.0179
9320	TRIP12	HTA11_866_3004761011	Human	Colorectum	AD	1.58e-04	-4.31e-01	0.096
9320	TRIP12	HTA11_8622_2000001021	Human	Colorectum	SER	2.43e-02	-5.42e-01	0.0528
9320	TRIP12	HTA11_10711_2000001011	Human	Colorectum	AD	4.94e-04	-3.93e-01	0.0338
9320	TRIP12	HTA11_7696_3000711011	Human	Colorectum	AD	2.19e-07	-3.79e-01	0.0674
9320	TRIP12	HTA11_99999970781_79442	Human	Colorectum	MSS	2.00e-03	-3.16e-01	0.294
9320	TRIP12	HTA11_99999973899_84307	Human	Colorectum	MSS	3.16e-02	-4.62e-01	0.2585
9320	TRIP12	HTA11_99999974143_84620	Human	Colorectum	MSS	6.28e-05	-3.42e-01	0.3005
9320	TRIP12	F007	Human	Colorectum	FAP	1.88e-02	-2.42e-01	0.1176
9320	TRIP12	A001-C-207	Human	Colorectum	FAP	1.87e-03	-2.05e-01	0.1278
9320	TRIP12	A015-C-203	Human	Colorectum	FAP	5.88e-38	-4.10e-01	-0.1294
9320	TRIP12	A015-C-204	Human	Colorectum	FAP	1.11e-06	-2.61e-01	-0.0228
9320	TRIP12	A014-C-040	Human	Colorectum	FAP	9.46e-05	-3.68e-01	-0.1184
9320	TRIP12	A002-C-201	Human	Colorectum	FAP	1.68e-16	-3.99e-01	0.0324
9320	TRIP12	A002-C-203	Human	Colorectum	FAP	2.74e-08	-2.24e-01	0.2786

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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
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
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
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:001657431	Oral cavity	NEOLP	histone ubiquitination	16/2005	47/18723	1.65e-05	2.83e-04	16
GO:003105631	Oral cavity	NEOLP	regulation of histone modification	34/2005	152/18723	2.31e-05	3.72e-04	34
GO:005105231	Oral cavity	NEOLP	regulation of DNA metabolic process	63/2005	359/18723	5.48e-05	7.44e-04	63
GO:200102031	Oral cavity	NEOLP	regulation of response to DNA damage stimulus	43/2005	219/18723	6.13e-05	8.19e-04	43
GO:004599513	Oral cavity	NEOLP	regulation of embryonic development	18/2005	64/18723	9.10e-05	1.12e-03	18
GO:007053421	Oral cavity	NEOLP	protein K63-linked ubiquitination	16/2005	56/18723	1.80e-04	1.97e-03	16
GO:003352221	Oral cavity	NEOLP	histone H2A ubiquitination	10/2005	26/18723	2.04e-04	2.19e-03	10
GO:200102121	Oral cavity	NEOLP	negative regulation of response to DNA damage stimulus	20/2005	81/18723	2.69e-04	2.71e-03	20
GO:00310572	Oral cavity	NEOLP	negative regulation of histone modification	12/2005	46/18723	2.66e-03	1.66e-02	12
GO:1902915	Oral cavity	NEOLP	negative regulation of protein polyubiquitination	5/2005	11/18723	3.72e-03	2.15e-02	5
GO:19029141	Oral cavity	NEOLP	regulation of protein polyubiquitination	8/2005	27/18723	5.85e-03	3.05e-02	8
GO:1900044	Oral cavity	NEOLP	regulation of protein K63-linked ubiquitination	5/2005	13/18723	8.62e-03	4.15e-02	5
GO:190332018	Prostate	BPH	regulation of protein modification by small protein conjugation or removal	90/3107	242/18723	7.37e-15	1.01e-12	90
GO:003139618	Prostate	BPH	regulation of protein ubiquitination	74/3107	210/18723	3.66e-11	2.39e-09	74
GO:190332118	Prostate	BPH	negative regulation of protein modification by small protein conjugation or removal	37/3107	95/18723	1.54e-07	3.54e-06	37
GO:00165706	Prostate	BPH	histone modification	120/3107	463/18723	1.73e-07	3.89e-06	120
GO:003139718	Prostate	BPH	negative regulation of protein ubiquitination	33/3107	83/18723	4.07e-07	8.42e-06	33
GO:00002099	Prostate	BPH	protein polyubiquitination	64/3107	236/18723	2.83e-05	3.31e-04	64
GO:200102015	Prostate	BPH	regulation of response to DNA damage stimulus	60/3107	219/18723	3.58e-05	3.92e-04	60
GO:00510529	Prostate	BPH	regulation of DNA metabolic process	89/3107	359/18723	4.07e-05	4.36e-04	89

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72

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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

TRIP12

SNV

Missense_Mutation

c.4696G>C

p.Asp1566His

p.D1566H

Q14669

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TRIP12

SNV

Missense_Mutation

c.4291N>T

p.Pro1431Ser

p.P1431S

Q14669

protein_coding

deleterious(0.03)

probably_damaging(0.939)

TCGA-A8-A09M-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

paclitaxel

TRIP12

SNV

Missense_Mutation

c.808N>A

p.Gln270Lys

p.Q270K

Q14669

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.696)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIP12

SNV

Missense_Mutation

novel

c.5551N>A

p.Glu1851Lys

p.E1851K

Q14669

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIP12

SNV

Missense_Mutation

novel

c.4592N>A

p.Arg1531Gln

p.R1531Q

Q14669

protein_coding

deleterious(0.02)

probably_damaging(0.945)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIP12

SNV

Missense_Mutation

novel

c.80N>C

p.Asp27Ala

p.D27A

Q14669

protein_coding

deleterious_low_confidence(0.01)

benign(0.091)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIP12

SNV

Missense_Mutation

c.1855N>A

p.Glu619Lys

p.E619K

Q14669

protein_coding

deleterious(0)

benign(0.001)

TCGA-AN-A0FK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TRIP12

SNV

Missense_Mutation

c.3370N>A

p.Ala1124Thr

p.A1124T

Q14669

protein_coding

tolerated(0.15)

benign(0.1)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

TRIP12

SNV

Missense_Mutation

rs373429636

c.2426N>T

p.Ala809Val

p.A809V

Q14669

protein_coding

tolerated(0.51)

possibly_damaging(0.868)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIP12

insertion

Frame_Shift_Ins

novel

c.5557_5558insGAATGGAAGAAGA

p.Lys1853ArgfsTer32

p.K1853Rfs*32

Q14669

protein_coding

TCGA-AN-A0AL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

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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