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: UFL1

Gene summary for UFL1

Gene summary.

Gene information	Species	Human
	Gene symbol	UFL1
	Gene ID	23376
	Gene name	UFM1 specific ligase 1
	Gene Alias	KIAA0776
	Cytomap	6q16.1
	Gene Type	protein-coding
	GO ID	GO:0001101
	UniProtAcc	O94874

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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
23376	UFL1	LZE4T	Human	Esophagus	ESCC	1.27e-15	5.12e-01	0.0811
23376	UFL1	LZE7T	Human	Esophagus	ESCC	2.77e-02	4.03e-01	0.0667
23376	UFL1	LZE8T	Human	Esophagus	ESCC	6.64e-07	2.02e-01	0.067
23376	UFL1	LZE20T	Human	Esophagus	ESCC	1.17e-03	1.98e-01	0.0662
23376	UFL1	LZE24T	Human	Esophagus	ESCC	1.36e-11	4.11e-01	0.0596
23376	UFL1	LZE21T	Human	Esophagus	ESCC	2.69e-04	3.14e-01	0.0655
23376	UFL1	P1T-E	Human	Esophagus	ESCC	1.97e-08	5.40e-01	0.0875
23376	UFL1	P2T-E	Human	Esophagus	ESCC	1.54e-39	8.06e-01	0.1177
23376	UFL1	P4T-E	Human	Esophagus	ESCC	4.33e-29	6.27e-01	0.1323
23376	UFL1	P5T-E	Human	Esophagus	ESCC	1.08e-20	4.64e-01	0.1327
23376	UFL1	P8T-E	Human	Esophagus	ESCC	3.25e-32	5.92e-01	0.0889
23376	UFL1	P9T-E	Human	Esophagus	ESCC	1.72e-08	2.53e-01	0.1131
23376	UFL1	P10T-E	Human	Esophagus	ESCC	5.17e-30	5.84e-01	0.116
23376	UFL1	P11T-E	Human	Esophagus	ESCC	3.79e-17	7.24e-01	0.1426
23376	UFL1	P12T-E	Human	Esophagus	ESCC	5.28e-38	7.66e-01	0.1122
23376	UFL1	P15T-E	Human	Esophagus	ESCC	1.26e-14	3.98e-01	0.1149
23376	UFL1	P16T-E	Human	Esophagus	ESCC	1.92e-55	9.89e-01	0.1153
23376	UFL1	P17T-E	Human	Esophagus	ESCC	2.87e-04	3.69e-01	0.1278
23376	UFL1	P20T-E	Human	Esophagus	ESCC	2.38e-17	3.49e-01	0.1124
23376	UFL1	P21T-E	Human	Esophagus	ESCC	1.48e-35	6.85e-01	0.1617

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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
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:001657015	Esophagus	ESCC	histone modification	323/8552	463/18723	2.61e-26	7.88e-24	323
GO:0042176111	Esophagus	ESCC	regulation of protein catabolic process	280/8552	391/18723	8.65e-26	2.39e-23	280
GO:001623617	Esophagus	ESCC	macroautophagy	216/8552	291/18723	1.94e-23	4.57e-21	216
GO:0022411111	Esophagus	ESCC	cellular component disassembly	305/8552	443/18723	1.94e-23	4.57e-21	305
GO:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:1903320111	Esophagus	ESCC	regulation of protein modification by small protein conjugation or removal	181/8552	242/18723	1.80e-20	2.60e-18	181
GO:1903362111	Esophagus	ESCC	regulation of cellular protein catabolic process	188/8552	255/18723	5.12e-20	6.62e-18	188
GO:001050617	Esophagus	ESCC	regulation of autophagy	220/8552	317/18723	6.72e-18	6.36e-16	220
GO:0035966111	Esophagus	ESCC	response to topologically incorrect protein	125/8552	159/18723	1.44e-17	1.27e-15	125
GO:1903050111	Esophagus	ESCC	regulation of proteolysis involved in cellular protein catabolic process	163/8552	221/18723	1.44e-17	1.27e-15	163
GO:0061136111	Esophagus	ESCC	regulation of proteasomal protein catabolic process	142/8552	187/18723	2.40e-17	2.00e-15	142
GO:0031396111	Esophagus	ESCC	regulation of protein ubiquitination	154/8552	210/18723	2.70e-16	2.04e-14	154
GO:0032434111	Esophagus	ESCC	regulation of proteasomal ubiquitin-dependent protein catabolic process	107/8552	134/18723	4.06e-16	2.93e-14	107
GO:2000058111	Esophagus	ESCC	regulation of ubiquitin-dependent protein catabolic process	125/8552	164/18723	1.17e-15	7.76e-14	125
GO:0006986111	Esophagus	ESCC	response to unfolded protein	107/8552	137/18723	7.01e-15	3.87e-13	107
GO:190300816	Esophagus	ESCC	organelle disassembly	89/8552	114/18723	1.36e-12	5.80e-11	89

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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

UFL1

SNV

Missense_Mutation

rs749425862

c.1609N>G

p.Ile537Val

p.I537V

O94874

protein_coding

tolerated(0.53)

benign(0.024)

TCGA-A2-A04P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxol

UFL1

SNV

Missense_Mutation

c.1139T>C

p.Met380Thr

p.M380T

O94874

protein_coding

deleterious(0)

possibly_damaging(0.526)

TCGA-A2-A1FV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

UFL1

SNV

Missense_Mutation

c.2232N>C

p.Lys744Asn

p.K744N

O94874

protein_coding

deleterious(0.05)

benign(0.185)

TCGA-AR-A1AI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

UFL1

SNV

Missense_Mutation

c.1525N>G

p.Leu509Val

p.L509V

O94874

protein_coding

deleterious(0)

possibly_damaging(0.784)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

UFL1

SNV

Missense_Mutation

c.1884C>G

p.Asn628Lys

p.N628K

O94874

protein_coding

tolerated(0.64)

benign(0.003)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

UFL1

SNV

Missense_Mutation

c.1309N>A

p.Gly437Arg

p.G437R

O94874

protein_coding

deleterious(0.01)

possibly_damaging(0.804)

TCGA-E9-A22H-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

UFL1

SNV

Missense_Mutation

rs777997396

c.2375N>T

p.Thr792Met

p.T792M

O94874

protein_coding

deleterious(0.01)

possibly_damaging(0.791)

TCGA-EW-A1IZ-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

UFL1

insertion

In_Frame_Ins

rs775473285

c.1752_1753insGAG

p.Leu584_Ile585insGlu

p.L584_I585insE

O94874

protein_coding

TCGA-BH-A0HN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

UFL1

insertion

In_Frame_Ins

rs762826701

c.1754_1755insAAG

p.Ile585_Phe586insSer

p.I585_F586insS

O94874

protein_coding

TCGA-BH-A0HN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

UFL1

SNV

Missense_Mutation

c.1507G>C

p.Glu503Gln

p.E503Q

O94874

protein_coding

tolerated(0.2)

benign(0.1)

TCGA-UC-A7PF-01

Cervix

cervical & endocervical cancer

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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