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: SEL1L

Gene summary for SEL1L

Gene summary.

Gene information	Species	Human
	Gene symbol	SEL1L
	Gene ID	6400
	Gene name	SEL1L adaptor subunit of ERAD E3 ubiquitin ligase
	Gene Alias	Hrd3
	Cytomap	14q31.1
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q9UBV2

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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
6400	SEL1L	LZE2T	Human	Esophagus	ESCC	5.31e-07	8.52e-01	0.082
6400	SEL1L	LZE4T	Human	Esophagus	ESCC	3.04e-17	4.69e-01	0.0811
6400	SEL1L	LZE5T	Human	Esophagus	ESCC	2.22e-05	5.75e-01	0.0514
6400	SEL1L	LZE7T	Human	Esophagus	ESCC	2.73e-03	2.07e-01	0.0667
6400	SEL1L	LZE8T	Human	Esophagus	ESCC	9.93e-05	1.67e-01	0.067
6400	SEL1L	LZE22T	Human	Esophagus	ESCC	3.63e-14	8.70e-01	0.068
6400	SEL1L	LZE24T	Human	Esophagus	ESCC	4.91e-17	3.67e-01	0.0596
6400	SEL1L	LZE21T	Human	Esophagus	ESCC	2.31e-03	3.10e-01	0.0655
6400	SEL1L	LZE6T	Human	Esophagus	ESCC	7.18e-06	2.04e-01	0.0845
6400	SEL1L	P1T-E	Human	Esophagus	ESCC	2.37e-11	4.78e-01	0.0875
6400	SEL1L	P2T-E	Human	Esophagus	ESCC	2.03e-21	3.86e-01	0.1177
6400	SEL1L	P4T-E	Human	Esophagus	ESCC	4.25e-20	4.62e-01	0.1323
6400	SEL1L	P5T-E	Human	Esophagus	ESCC	8.04e-21	3.15e-01	0.1327
6400	SEL1L	P8T-E	Human	Esophagus	ESCC	1.40e-30	5.56e-01	0.0889
6400	SEL1L	P9T-E	Human	Esophagus	ESCC	1.11e-08	1.69e-01	0.1131
6400	SEL1L	P10T-E	Human	Esophagus	ESCC	6.69e-38	7.68e-01	0.116
6400	SEL1L	P11T-E	Human	Esophagus	ESCC	1.10e-16	9.05e-01	0.1426
6400	SEL1L	P12T-E	Human	Esophagus	ESCC	8.10e-29	7.52e-01	0.1122
6400	SEL1L	P15T-E	Human	Esophagus	ESCC	5.27e-46	1.12e+00	0.1149
6400	SEL1L	P16T-E	Human	Esophagus	ESCC	2.41e-24	4.95e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:0031647111	Esophagus	ESCC	regulation of protein stability	223/8552	298/18723	5.76e-25	1.52e-22	223
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:0050821111	Esophagus	ESCC	protein stabilization	140/8552	191/18723	6.50e-15	3.61e-13	140
GO:003650315	Esophagus	ESCC	ERAD pathway	82/8552	107/18723	5.80e-11	1.84e-09	82
GO:003043314	Esophagus	ESCC	ubiquitin-dependent ERAD pathway	66/8552	85/18723	1.64e-09	3.78e-08	66
GO:003252714	Esophagus	ESCC	protein exit from endoplasmic reticulum	37/8552	48/18723	8.99e-06	8.65e-05	37
GO:00072197	Esophagus	ESCC	Notch signaling pathway	106/8552	172/18723	1.74e-05	1.55e-04	106
GO:003097014	Esophagus	ESCC	retrograde protein transport, ER to cytosol	23/8552	29/18723	2.25e-04	1.40e-03	23
GO:190351314	Esophagus	ESCC	endoplasmic reticulum to cytosol transport	23/8552	29/18723	2.25e-04	1.40e-03	23
GO:00464864	Esophagus	ESCC	glycerolipid metabolic process	211/8552	392/18723	6.51e-04	3.46e-03	211
GO:000930617	Esophagus	ESCC	protein secretion	190/8552	359/18723	3.22e-03	1.34e-02	190
GO:003559217	Esophagus	ESCC	establishment of protein localization to extracellular region	190/8552	360/18723	3.77e-03	1.53e-02	190
GO:007169210	Esophagus	ESCC	protein localization to extracellular region	193/8552	368/18723	5.01e-03	1.92e-02	193
GO:00431617	Liver	NAFLD	proteasome-mediated ubiquitin-dependent protein catabolic process	91/1882	412/18723	3.00e-13	1.75e-10	91
GO:00104987	Liver	NAFLD	proteasomal protein catabolic process	101/1882	490/18723	1.35e-12	6.09e-10	101
GO:00316477	Liver	NAFLD	regulation of protein stability	61/1882	298/18723	5.00e-08	4.71e-06	61
GO:00066413	Liver	NAFLD	triglyceride metabolic process	29/1882	100/18723	9.51e-08	7.62e-06	29
GO:00066392	Liver	NAFLD	acylglycerol metabolic process	32/1882	128/18723	8.82e-07	4.60e-05	32

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141210	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113
hsa0414138	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113
hsa0414128	Prostate	BPH	Protein processing in endoplasmic reticulum	97/1718	174/8465	2.37e-25	1.30e-23	8.07e-24	97
hsa04141112	Prostate	BPH	Protein processing in endoplasmic reticulum	97/1718	174/8465	2.37e-25	1.30e-23	8.07e-24	97
hsa0414129	Prostate	Tumor	Protein processing in endoplasmic reticulum	99/1791	174/8465	2.58e-25	1.71e-23	1.06e-23	99
hsa0414137	Prostate	Tumor	Protein processing in endoplasmic reticulum	99/1791	174/8465	2.58e-25	1.71e-23	1.06e-23	99

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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

SEL1L

SNV

Missense_Mutation

c.1324N>A

p.Ala442Thr

p.A442T

Q9UBV2

protein_coding

deleterious(0.02)

possibly_damaging(0.765)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEL1L

SNV

Missense_Mutation

c.950N>G

p.His317Arg

p.H317R

Q9UBV2

protein_coding

deleterious(0.01)

possibly_damaging(0.811)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

SEL1L

SNV

Missense_Mutation

c.247G>C

p.Glu83Gln

p.E83Q

Q9UBV2

protein_coding

tolerated_low_confidence(0.09)

benign(0.039)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SEL1L

insertion

In_Frame_Ins

novel

c.2199_2200insAAAACAGTGTGTGCC

p.Leu733_Asp734insLysThrValCysAla

p.L733_D734insKTVCA

Q9UBV2

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SEL1L

insertion

Nonsense_Mutation

novel

c.2197_2198insATTGAGTACGTGCTTTGAGAAAACATTTC

p.Leu733HisfsTer2

p.L733Hfs*2

Q9UBV2

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

SEL1L

insertion

Nonsense_Mutation

novel

c.1261_1262insAAAGGGTTAATCATAACCAACTCATGCTATA

p.Ser421Ter

p.S421*

Q9UBV2

protein_coding

TCGA-AO-A03O-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

SEL1L

SNV

Missense_Mutation

novel

c.361N>G

p.Thr121Ala

p.T121A

Q9UBV2

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.97)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SEL1L

SNV

Missense_Mutation

c.967A>G

p.Asn323Asp

p.N323D

Q9UBV2

protein_coding

tolerated(0.27)

benign(0.079)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

SEL1L

SNV

Missense_Mutation

c.102T>G

p.Asp34Glu

p.D34E

Q9UBV2

protein_coding

tolerated_low_confidence(0.74)

benign(0)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

SEL1L

SNV

Missense_Mutation

c.1576G>A

p.Ala526Thr

p.A526T

Q9UBV2

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-AA-3710-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

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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