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: THRAP3

Gene summary for THRAP3

Gene summary.

Gene information	Species	Human
	Gene symbol	THRAP3
	Gene ID	9967
	Gene name	thyroid hormone receptor associated protein 3
	Gene Alias	BCLAF2
	Cytomap	1p34.3
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	Q9Y2W1

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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
9967	THRAP3	HTA11_347_2000001011	Human	Colorectum	AD	1.63e-08	5.73e-01	-0.1954
9967	THRAP3	HTA11_411_2000001011	Human	Colorectum	SER	5.63e-03	7.64e-01	-0.2602
9967	THRAP3	HTA11_1391_2000001011	Human	Colorectum	AD	2.00e-02	5.13e-01	-0.059
9967	THRAP3	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.56e-05	1.12e+00	0.3487
9967	THRAP3	HTA11_99999965104_69814	Human	Colorectum	MSS	4.84e-03	5.39e-01	0.281
9967	THRAP3	A002-C-010	Human	Colorectum	FAP	1.92e-03	-1.85e-01	0.242
9967	THRAP3	A015-C-203	Human	Colorectum	FAP	1.45e-23	-3.12e-01	-0.1294
9967	THRAP3	A015-C-204	Human	Colorectum	FAP	5.84e-04	-1.95e-01	-0.0228
9967	THRAP3	A014-C-040	Human	Colorectum	FAP	6.58e-04	-3.19e-01	-0.1184
9967	THRAP3	A002-C-201	Human	Colorectum	FAP	9.63e-11	-3.15e-01	0.0324
9967	THRAP3	A002-C-203	Human	Colorectum	FAP	5.96e-07	-1.87e-01	0.2786
9967	THRAP3	A001-C-119	Human	Colorectum	FAP	2.12e-03	-4.78e-02	-0.1557
9967	THRAP3	A001-C-108	Human	Colorectum	FAP	8.24e-14	-1.66e-01	-0.0272
9967	THRAP3	A002-C-205	Human	Colorectum	FAP	5.34e-18	-2.18e-01	-0.1236
9967	THRAP3	A001-C-104	Human	Colorectum	FAP	9.88e-03	-8.36e-02	0.0184
9967	THRAP3	A015-C-005	Human	Colorectum	FAP	1.39e-02	-2.04e-01	-0.0336
9967	THRAP3	A015-C-006	Human	Colorectum	FAP	1.40e-12	-7.38e-03	-0.0994
9967	THRAP3	A015-C-106	Human	Colorectum	FAP	4.26e-11	-1.84e-01	-0.0511
9967	THRAP3	A002-C-114	Human	Colorectum	FAP	4.02e-14	-2.71e-01	-0.1561
9967	THRAP3	A015-C-104	Human	Colorectum	FAP	3.21e-22	-1.45e-01	-0.1899

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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
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:000037513	Lung	AIS	RNA splicing, via transesterification reactions	49/1849	324/18723	1.69e-03	1.93e-02	49
GO:003312013	Lung	AIS	positive regulation of RNA splicing	10/1849	37/18723	2.48e-03	2.55e-02	10
GO:190331213	Lung	AIS	negative regulation of mRNA metabolic process	18/1849	92/18723	3.54e-03	3.34e-02	18
GO:004348433	Lung	MIAC	regulation of RNA splicing	32/967	148/18723	3.60e-12	9.23e-09	32
GO:190331132	Lung	MIAC	regulation of mRNA metabolic process	45/967	288/18723	2.75e-11	4.70e-08	45
GO:004802432	Lung	MIAC	regulation of mRNA splicing, via spliceosome	24/967	101/18723	2.28e-10	2.92e-07	24
GO:005068432	Lung	MIAC	regulation of mRNA processing	26/967	137/18723	7.19e-09	4.94e-06	26
GO:000038122	Lung	MIAC	regulation of alternative mRNA splicing, via spliceosome	14/967	60/18723	1.64e-06	2.10e-04	14
GO:004348831	Lung	MIAC	regulation of mRNA stability	23/967	158/18723	6.62e-06	6.29e-04	23
GO:004348731	Lung	MIAC	regulation of RNA stability	24/967	170/18723	7.20e-06	6.53e-04	24
GO:006101331	Lung	MIAC	regulation of mRNA catabolic process	23/967	166/18723	1.52e-05	1.07e-03	23
GO:000838023	Lung	MIAC	RNA splicing	44/967	434/18723	1.56e-05	1.07e-03	44
GO:000640231	Lung	MIAC	mRNA catabolic process	28/967	232/18723	2.65e-05	1.66e-03	28
GO:000038022	Lung	MIAC	alternative mRNA splicing, via spliceosome	14/967	77/18723	3.50e-05	1.97e-03	14
GO:190331223	Lung	MIAC	negative regulation of mRNA metabolic process	15/967	92/18723	6.98e-05	3.38e-03	15
GO:190331322	Lung	MIAC	positive regulation of mRNA metabolic process	17/967	118/18723	1.17e-04	4.92e-03	17
GO:000037723	Lung	MIAC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	33/967	320/18723	1.27e-04	5.13e-03	33
GO:000039823	Lung	MIAC	mRNA splicing, via spliceosome	33/967	320/18723	1.27e-04	5.13e-03	33
GO:000037523	Lung	MIAC	RNA splicing, via transesterification reactions	33/967	324/18723	1.61e-04	6.19e-03	33
GO:003133033	Lung	MIAC	negative regulation of cellular catabolic process	28/967	262/18723	2.23e-04	7.67e-03	28

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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

THRAP3

SNV

Missense_Mutation

novel

c.953N>A

p.Gly318Asp

p.G318D

Q9Y2W1

protein_coding

tolerated(0.22)

benign(0.215)

TCGA-A7-A6VX-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

THRAP3

SNV

Missense_Mutation

c.2428N>A

p.Asp810Asn

p.D810N

Q9Y2W1

protein_coding

tolerated(0.69)

possibly_damaging(0.873)

TCGA-A8-A07B-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

THRAP3

SNV

Missense_Mutation

c.869N>A

p.Gly290Asp

p.G290D

Q9Y2W1

protein_coding

tolerated(0.07)

possibly_damaging(0.726)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

THRAP3

SNV

Missense_Mutation

c.880N>G

p.Gln294Glu

p.Q294E

Q9Y2W1

protein_coding

tolerated(0.12)

possibly_damaging(0.79)

TCGA-BH-A1EV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

THRAP3

SNV

Missense_Mutation

c.144N>C

p.Arg48Ser

p.R48S

Q9Y2W1

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.994)

TCGA-BH-A1FU-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

THRAP3

SNV

Missense_Mutation

rs749716914

c.2080G>A

p.Asp694Asn

p.D694N

Q9Y2W1

protein_coding

deleterious(0.02)

possibly_damaging(0.709)

TCGA-C8-A131-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

THRAP3

SNV

Missense_Mutation

c.2081A>T

p.Asp694Val

p.D694V

Q9Y2W1

protein_coding

deleterious(0)

possibly_damaging(0.848)

TCGA-C8-A131-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

THRAP3

SNV

Missense_Mutation

c.302N>C

p.Arg101Pro

p.R101P

Q9Y2W1

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

THRAP3

SNV

Missense_Mutation

c.1403N>T

p.Ser468Leu

p.S468L

Q9Y2W1

protein_coding

tolerated(0.67)

benign(0.15)

TCGA-E2-A9RU-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

THRAP3

SNV

Missense_Mutation

c.320A>C

p.Tyr107Ser

p.Y107S

Q9Y2W1

protein_coding

deleterious(0.01)

probably_damaging(0.918)

TCGA-E9-A1N8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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