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:001943921	Liver	HCC	aromatic compound catabolic process	309/7958	467/18723	1.56e-25	4.94e-23	309
GO:000037522	Liver	HCC	RNA splicing, via transesterification reactions	228/7958	324/18723	1.47e-24	4.06e-22	228
GO:000640121	Liver	HCC	RNA catabolic process	201/7958	278/18723	3.88e-24	1.02e-21	201
GO:003465521	Liver	HCC	nucleobase-containing compound catabolic process	273/7958	407/18723	4.84e-24	1.23e-21	273
GO:000037722	Liver	HCC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	224/7958	320/18723	1.16e-23	2.62e-21	224
GO:000039822	Liver	HCC	mRNA splicing, via spliceosome	224/7958	320/18723	1.16e-23	2.62e-21	224
GO:190331121	Liver	HCC	regulation of mRNA metabolic process	205/7958	288/18723	3.38e-23	6.90e-21	205
GO:000640221	Liver	HCC	mRNA catabolic process	169/7958	232/18723	4.50e-21	6.96e-19	169
GO:004348422	Liver	HCC	regulation of RNA splicing	113/7958	148/18723	4.32e-17	4.15e-15	113
GO:005068421	Liver	HCC	regulation of mRNA processing	106/7958	137/18723	7.64e-17	7.12e-15	106
GO:004348721	Liver	HCC	regulation of RNA stability	119/7958	170/18723	3.20e-13	1.71e-11	119
GO:000095621	Liver	HCC	nuclear-transcribed mRNA catabolic process	84/7958	112/18723	2.54e-12	1.18e-10	84
GO:004348821	Liver	HCC	regulation of mRNA stability	110/7958	158/18723	4.36e-12	1.93e-10	110
GO:006101321	Liver	HCC	regulation of mRNA catabolic process	114/7958	166/18723	7.38e-12	3.12e-10	114
GO:000989522	Liver	HCC	negative regulation of catabolic process	196/7958	320/18723	7.98e-12	3.35e-10	196
GO:003133022	Liver	HCC	negative regulation of cellular catabolic process	164/7958	262/18723	3.52e-11	1.35e-09	164
GO:190331321	Liver	HCC	positive regulation of mRNA metabolic process	85/7958	118/18723	7.10e-11	2.56e-09	85
GO:004802422	Liver	HCC	regulation of mRNA splicing, via spliceosome	74/7958	101/18723	3.29e-10	1.10e-08	74
GO:190331222	Liver	HCC	negative regulation of mRNA metabolic process	63/7958	92/18723	4.14e-07	6.97e-06	63
GO:000038021	Liver	HCC	alternative mRNA splicing, via spliceosome	52/7958	77/18723	7.87e-06	9.27e-05	52

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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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