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: GNL1

Gene summary for GNL1

Gene summary.

Gene information	Species	Human
	Gene symbol	GNL1
	Gene ID	2794
	Gene name	G protein nucleolar 1 (putative)
	Gene Alias	HSR1
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0002250
	UniProtAcc	A0A024RCR2

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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
2794	GNL1	LZE4T	Human	Esophagus	ESCC	1.00e-14	3.29e-01	0.0811
2794	GNL1	LZE5T	Human	Esophagus	ESCC	4.85e-04	6.03e-02	0.0514
2794	GNL1	LZE7T	Human	Esophagus	ESCC	8.79e-05	3.02e-01	0.0667
2794	GNL1	LZE8T	Human	Esophagus	ESCC	1.45e-08	1.95e-01	0.067
2794	GNL1	LZE20T	Human	Esophagus	ESCC	1.83e-09	3.37e-02	0.0662
2794	GNL1	LZE22D1	Human	Esophagus	HGIN	7.09e-06	1.29e-01	0.0595
2794	GNL1	LZE22T	Human	Esophagus	ESCC	3.05e-03	5.50e-01	0.068
2794	GNL1	LZE24T	Human	Esophagus	ESCC	6.24e-22	6.59e-01	0.0596
2794	GNL1	LZE21T	Human	Esophagus	ESCC	3.21e-05	3.00e-01	0.0655
2794	GNL1	LZE6T	Human	Esophagus	ESCC	3.53e-07	2.69e-01	0.0845
2794	GNL1	P1T-E	Human	Esophagus	ESCC	3.10e-08	6.85e-01	0.0875
2794	GNL1	P2T-E	Human	Esophagus	ESCC	1.17e-49	9.18e-01	0.1177
2794	GNL1	P4T-E	Human	Esophagus	ESCC	1.88e-26	7.26e-01	0.1323
2794	GNL1	P5T-E	Human	Esophagus	ESCC	1.45e-12	2.09e-01	0.1327
2794	GNL1	P8T-E	Human	Esophagus	ESCC	6.16e-29	4.74e-01	0.0889
2794	GNL1	P9T-E	Human	Esophagus	ESCC	2.40e-12	3.64e-01	0.1131
2794	GNL1	P10T-E	Human	Esophagus	ESCC	7.22e-16	3.84e-01	0.116
2794	GNL1	P11T-E	Human	Esophagus	ESCC	7.84e-17	7.26e-01	0.1426
2794	GNL1	P12T-E	Human	Esophagus	ESCC	9.69e-31	5.84e-01	0.1122
2794	GNL1	P15T-E	Human	Esophagus	ESCC	7.54e-22	5.12e-01	0.1149

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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:00070157	Liver	NAFLD	actin filament organization	78/1882	442/18723	5.44e-07	3.21e-05	78
GO:00310326	Liver	NAFLD	actomyosin structure organization	41/1882	196/18723	4.26e-06	1.66e-04	41
GO:00510564	Liver	NAFLD	regulation of small GTPase mediated signal transduction	56/1882	302/18723	4.62e-06	1.75e-04	56
GO:19029037	Liver	NAFLD	regulation of supramolecular fiber organization	66/1882	383/18723	8.97e-06	2.96e-04	66
GO:00329707	Liver	NAFLD	regulation of actin filament-based process	66/1882	397/18723	2.92e-05	7.72e-04	66
GO:00329567	Liver	NAFLD	regulation of actin cytoskeleton organization	60/1882	358/18723	5.20e-05	1.20e-03	60
GO:01100537	Liver	NAFLD	regulation of actin filament organization	49/1882	278/18723	6.88e-05	1.46e-03	49
GO:00510583	Liver	NAFLD	negative regulation of small GTPase mediated signal transduction	16/1882	56/18723	8.53e-05	1.72e-03	16
GO:00300387	Liver	NAFLD	contractile actin filament bundle assembly	24/1882	106/18723	1.10e-04	2.13e-03	24
GO:00431497	Liver	NAFLD	stress fiber assembly	24/1882	106/18723	1.10e-04	2.13e-03	24
GO:01100207	Liver	NAFLD	regulation of actomyosin structure organization	22/1882	100/18723	3.22e-04	4.98e-03	22
GO:00514927	Liver	NAFLD	regulation of stress fiber assembly	20/1882	91/18723	5.98e-04	7.95e-03	20
GO:00615727	Liver	NAFLD	actin filament bundle organization	29/1882	161/18723	1.37e-03	1.54e-02	29
GO:00322317	Liver	NAFLD	regulation of actin filament bundle assembly	21/1882	105/18723	1.60e-03	1.71e-02	21
GO:00510177	Liver	NAFLD	actin filament bundle assembly	28/1882	157/18723	1.91e-03	1.93e-02	28
GO:000701512	Liver	Cirrhotic	actin filament organization	171/4634	442/18723	3.93e-11	2.30e-09	171
GO:190290312	Liver	Cirrhotic	regulation of supramolecular fiber organization	148/4634	383/18723	8.85e-10	4.08e-08	148
GO:003297012	Liver	Cirrhotic	regulation of actin filament-based process	152/4634	397/18723	1.12e-09	5.00e-08	152
GO:003295612	Liver	Cirrhotic	regulation of actin cytoskeleton organization	136/4634	358/18723	1.47e-08	5.49e-07	136
GO:005101712	Liver	Cirrhotic	actin filament bundle assembly	69/4634	157/18723	1.06e-07	3.05e-06	69

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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

GNL1

SNV

Missense_Mutation

novel

c.775N>T

p.Arg259Trp

p.R259W

P36915

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

GNL1

insertion

In_Frame_Ins

novel

c.1469_1470insTTCTCTCCTCTTCTCCCTTCTTTTTTCATGCATTCT

p.Thr490_Ala491insSerLeuLeuPheSerLeuLeuPheSerCysIleLeu

p.T490_A491insSLLFSLLFSCIL

P36915

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

GNL1

insertion

Nonsense_Mutation

novel

c.1381_1382insTGTTCAGCAATCTGCACATAGGAAGTTGAATGAATGGATGAATG

p.His461LeufsTer10

p.H461Lfs*10

P36915

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

GNL1

insertion

Frame_Shift_Ins

novel

c.540_541insGGACCGAGACATCCAGAGCAATC

p.Leu181GlyfsTer13

p.L181Gfs*13

P36915

protein_coding

TCGA-A8-A08B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

GNL1

SNV

Missense_Mutation

rs758752898

c.904G>A

p.Val302Met

p.V302M

P36915

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GNL1

SNV

Missense_Mutation

novel

c.775C>T

p.Arg259Trp

p.R259W

P36915

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GNL1

SNV

Missense_Mutation

c.1438N>A

p.Glu480Lys

p.E480K

P36915

protein_coding

deleterious(0.01)

benign(0.054)

TCGA-C5-A7CM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GNL1

SNV

Missense_Mutation

c.494C>T

p.Ser165Phe

p.S165F

P36915

protein_coding

deleterious(0.04)

benign(0.037)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

GNL1

SNV

Missense_Mutation

c.449G>A

p.Arg150Gln

p.R150Q

P36915

protein_coding

tolerated(0.18)

benign(0.029)

TCGA-AA-3494-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folinic

GNL1

SNV

Missense_Mutation

rs757866378

c.824N>A

p.Arg275Gln

p.R275Q

P36915

protein_coding

deleterious(0.01)

benign(0.278)

TCGA-AA-3966-01

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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