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: HECTD1

Gene summary for HECTD1

Gene summary.

Gene information	Species	Human
	Gene symbol	HECTD1
	Gene ID	25831
	Gene name	HECT domain E3 ubiquitin protein ligase 1
	Gene Alias	EULIR
	Cytomap	14q12
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q9ULT8

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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
25831	HECTD1	HTA11_3410_2000001011	Human	Colorectum	AD	1.06e-19	-5.59e-01	0.0155
25831	HECTD1	HTA11_347_2000001011	Human	Colorectum	AD	1.18e-05	4.85e-01	-0.1954
25831	HECTD1	HTA11_3361_2000001011	Human	Colorectum	AD	4.17e-09	-5.29e-01	-0.1207
25831	HECTD1	HTA11_5212_2000001011	Human	Colorectum	AD	6.67e-03	-5.25e-01	-0.2061
25831	HECTD1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.99e-06	-4.19e-01	0.3859
25831	HECTD1	HTA11_99999973899_84307	Human	Colorectum	MSS	1.98e-03	-5.06e-01	0.2585
25831	HECTD1	HTA11_99999974143_84620	Human	Colorectum	MSS	5.90e-08	-4.61e-01	0.3005
25831	HECTD1	F007	Human	Colorectum	FAP	3.76e-04	-3.83e-01	0.1176
25831	HECTD1	A001-C-207	Human	Colorectum	FAP	1.15e-03	-1.84e-01	0.1278
25831	HECTD1	A015-C-203	Human	Colorectum	FAP	3.58e-31	-3.49e-01	-0.1294
25831	HECTD1	A015-C-204	Human	Colorectum	FAP	9.65e-05	-2.46e-01	-0.0228
25831	HECTD1	A014-C-040	Human	Colorectum	FAP	6.94e-05	-3.05e-01	-0.1184
25831	HECTD1	A002-C-201	Human	Colorectum	FAP	1.46e-15	-3.66e-01	0.0324
25831	HECTD1	A002-C-203	Human	Colorectum	FAP	1.05e-06	-1.69e-01	0.2786
25831	HECTD1	A001-C-119	Human	Colorectum	FAP	2.16e-05	-1.45e-01	-0.1557
25831	HECTD1	A001-C-108	Human	Colorectum	FAP	1.47e-19	-1.75e-01	-0.0272
25831	HECTD1	A002-C-205	Human	Colorectum	FAP	6.00e-25	-1.93e-01	-0.1236
25831	HECTD1	A001-C-104	Human	Colorectum	FAP	1.80e-02	-7.51e-02	0.0184
25831	HECTD1	A015-C-005	Human	Colorectum	FAP	1.02e-09	-4.07e-01	-0.0336
25831	HECTD1	A015-C-006	Human	Colorectum	FAP	3.28e-16	-4.08e-01	-0.0994

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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:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:0072659	Colorectum	AD	protein localization to plasma membrane	122/3918	284/18723	2.86e-17	1.49e-14	122
GO:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:1903362	Colorectum	AD	regulation of cellular protein catabolic process	109/3918	255/18723	2.14e-15	6.08e-13	109
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0031331	Colorectum	AD	positive regulation of cellular catabolic process	156/3918	427/18723	4.68e-14	1.05e-11	156
GO:1990778	Colorectum	AD	protein localization to cell periphery	129/3918	333/18723	5.51e-14	1.15e-11	129
GO:1903050	Colorectum	AD	regulation of proteolysis involved in cellular protein catabolic process	92/3918	221/18723	2.04e-12	3.19e-10	92
GO:0045732	Colorectum	AD	positive regulation of protein catabolic process	92/3918	231/18723	3.85e-11	4.47e-09	92
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:1905475	Colorectum	AD	regulation of protein localization to membrane	73/3918	175/18723	3.37e-10	2.93e-08	73
GO:0045862	Colorectum	AD	positive regulation of proteolysis	129/3918	372/18723	4.04e-10	3.46e-08	129
GO:0061136	Colorectum	AD	regulation of proteasomal protein catabolic process	75/3918	187/18723	1.65e-09	1.20e-07	75
GO:2000058	Colorectum	AD	regulation of ubiquitin-dependent protein catabolic process	68/3918	164/18723	1.82e-09	1.31e-07	68
GO:1903076	Colorectum	AD	regulation of protein localization to plasma membrane	48/3918	104/18723	7.17e-09	4.36e-07	48
GO:1904375	Colorectum	AD	regulation of protein localization to cell periphery	54/3918	125/18723	1.52e-08	9.00e-07	54
GO:1903364	Colorectum	AD	positive regulation of cellular protein catabolic process	62/3918	155/18723	4.66e-08	2.51e-06	62
GO:0032434	Colorectum	AD	regulation of proteasomal ubiquitin-dependent protein catabolic process	54/3918	134/18723	2.51e-07	1.02e-05	54
GO:1903052	Colorectum	AD	positive regulation of proteolysis involved in cellular protein catabolic process	53/3918	133/18723	4.93e-07	1.85e-05	53
GO:2000060	Colorectum	AD	positive regulation of ubiquitin-dependent protein catabolic process	44/3918	107/18723	1.65e-06	5.03e-05	44

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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

HECTD1

SNV

Missense_Mutation

c.6715N>A

p.Glu2239Lys

p.E2239K

Q9ULT8

protein_coding

tolerated(0.11)

probably_damaging(0.973)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

HECTD1

SNV

Missense_Mutation

c.140N>G

p.Thr47Arg

p.T47R

Q9ULT8

protein_coding

deleterious(0.01)

benign(0.148)

TCGA-A2-A0YM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HECTD1

SNV

Missense_Mutation

c.2228N>G

p.Pro743Arg

p.P743R

Q9ULT8

protein_coding

deleterious(0)

possibly_damaging(0.896)

TCGA-A8-A08P-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

HECTD1

SNV

Missense_Mutation

c.5992G>C

p.Glu1998Gln

p.E1998Q

Q9ULT8

protein_coding

deleterious(0.01)

benign(0.115)

TCGA-A8-A095-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

HECTD1

SNV

Missense_Mutation

rs755152978

c.3005N>A

p.Arg1002Gln

p.R1002Q

Q9ULT8

protein_coding

deleterious(0)

probably_damaging(0.916)

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

HECTD1

SNV

Missense_Mutation

rs748524391

c.4411N>T

p.Arg1471Cys

p.R1471C

Q9ULT8

protein_coding

deleterious(0.02)

benign(0.336)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HECTD1

SNV

Missense_Mutation

c.1259N>T

p.Ala420Val

p.A420V

Q9ULT8

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-AO-A0J9-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

HECTD1

SNV

Missense_Mutation

c.1510G>A

p.Glu504Lys

p.E504K

Q9ULT8

protein_coding

tolerated(0.26)

benign(0.009)

TCGA-AR-A0TP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

HECTD1

SNV

Missense_Mutation

c.4696C>G

p.Leu1566Val

p.L1566V

Q9ULT8

protein_coding

tolerated(0.29)

probably_damaging(0.931)

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HECTD1

SNV

Missense_Mutation

novel

c.3858N>T

p.Trp1286Cys

p.W1286C

Q9ULT8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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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