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: QARS

Gene summary for QARS

Gene summary.

Gene information	Species	Human
	Gene symbol	QARS
	Gene ID	5859
	Gene name	glutaminyl-tRNA synthetase 1
	Gene Alias	GLNRS
	Cytomap	3p21.31
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	B7Z840

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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
5859	QARS	HTA11_99999970781_79442	Human	Colorectum	MSS	9.24e-45	9.16e-01	0.294
5859	QARS	HTA11_99999965062_69753	Human	Colorectum	MSI-H	4.28e-12	1.65e+00	0.3487
5859	QARS	HTA11_99999965104_69814	Human	Colorectum	MSS	1.46e-35	1.36e+00	0.281
5859	QARS	HTA11_99999971662_82457	Human	Colorectum	MSS	1.98e-95	1.94e+00	0.3859
5859	QARS	HTA11_99999973899_84307	Human	Colorectum	MSS	1.00e-23	1.01e+00	0.2585
5859	QARS	HTA11_99999974143_84620	Human	Colorectum	MSS	1.12e-51	1.10e+00	0.3005
5859	QARS	LZE2T	Human	Esophagus	ESCC	1.39e-04	1.70e-01	0.082
5859	QARS	LZE4T	Human	Esophagus	ESCC	1.45e-07	-1.81e-02	0.0811
5859	QARS	LZE5T	Human	Esophagus	ESCC	7.39e-07	4.45e-02	0.0514
5859	QARS	LZE7T	Human	Esophagus	ESCC	8.55e-09	8.61e-02	0.0667
5859	QARS	LZE8T	Human	Esophagus	ESCC	6.35e-08	-1.11e-01	0.067
5859	QARS	LZE20T	Human	Esophagus	ESCC	1.80e-06	-1.69e-01	0.0662
5859	QARS	LZE22D1	Human	Esophagus	HGIN	3.68e-06	-7.08e-02	0.0595
5859	QARS	LZE24T	Human	Esophagus	ESCC	7.47e-16	1.62e-01	0.0596
5859	QARS	LZE6T	Human	Esophagus	ESCC	2.09e-04	-1.09e-01	0.0845
5859	QARS	P1T-E	Human	Esophagus	ESCC	3.62e-05	1.96e-01	0.0875
5859	QARS	P2T-E	Human	Esophagus	ESCC	3.47e-33	2.65e-01	0.1177
5859	QARS	P4T-E	Human	Esophagus	ESCC	1.62e-15	2.99e-01	0.1323
5859	QARS	P5T-E	Human	Esophagus	ESCC	3.09e-13	-1.04e-01	0.1327
5859	QARS	P8T-E	Human	Esophagus	ESCC	1.23e-10	1.80e-01	0.0889

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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
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:2001233	Colorectum	AD	regulation of apoptotic signaling pathway	119/3918	356/18723	2.14e-08	1.21e-06	119
GO:0010563	Colorectum	AD	negative regulation of phosphorus metabolic process	130/3918	442/18723	1.26e-05	2.76e-04	130
GO:2001234	Colorectum	AD	negative regulation of apoptotic signaling pathway	74/3918	224/18723	1.49e-05	3.18e-04	74
GO:0045936	Colorectum	AD	negative regulation of phosphate metabolic process	129/3918	441/18723	1.81e-05	3.76e-04	129
GO:0051348	Colorectum	AD	negative regulation of transferase activity	85/3918	268/18723	2.07e-05	4.19e-04	85
GO:0042326	Colorectum	AD	negative regulation of phosphorylation	112/3918	385/18723	8.02e-05	1.27e-03	112
GO:0001933	Colorectum	AD	negative regulation of protein phosphorylation	101/3918	342/18723	9.39e-05	1.42e-03	101
GO:0006418	Colorectum	AD	tRNA aminoacylation for protein translation	19/3918	41/18723	2.37e-04	3.03e-03	19
GO:0043409	Colorectum	AD	negative regulation of MAPK cascade	57/3918	180/18723	4.61e-04	5.14e-03	57
GO:0051403	Colorectum	AD	stress-activated MAPK cascade	72/3918	239/18723	4.77e-04	5.25e-03	72
GO:0031098	Colorectum	AD	stress-activated protein kinase signaling cascade	74/3918	247/18723	4.80e-04	5.27e-03	74
GO:0006469	Colorectum	AD	negative regulation of protein kinase activity	65/3918	212/18723	5.21e-04	5.62e-03	65
GO:0033673	Colorectum	AD	negative regulation of kinase activity	71/3918	237/18723	6.18e-04	6.47e-03	71
GO:0043039	Colorectum	AD	tRNA aminoacylation	19/3918	44/18723	7.13e-04	7.21e-03	19
GO:0043038	Colorectum	AD	amino acid activation	19/3918	45/18723	9.94e-04	9.28e-03	19
GO:0006520	Colorectum	AD	cellular amino acid metabolic process	81/3918	284/18723	1.37e-03	1.19e-02	81
GO:0070302	Colorectum	AD	regulation of stress-activated protein kinase signaling cascade	58/3918	195/18723	2.21e-03	1.74e-02	58
GO:0032872	Colorectum	AD	regulation of stress-activated MAPK cascade	57/3918	192/18723	2.51e-03	1.92e-02	57
GO:0032873	Colorectum	AD	negative regulation of stress-activated MAPK cascade	19/3918	51/18723	5.44e-03	3.55e-02	19
GO:0070303	Colorectum	AD	negative regulation of stress-activated protein kinase signaling cascade	19/3918	51/18723	5.44e-03	3.55e-02	19

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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

QARS

SNV

Missense_Mutation

c.2311N>C

p.Asp771His

p.D771H

P47897

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

QARS

SNV

Missense_Mutation

c.2236N>G

p.Leu746Val

p.L746V

P47897

protein_coding

tolerated(0.56)

benign(0.006)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

QARS

SNV

Missense_Mutation

c.852N>G

p.Ile284Met

p.I284M

P47897

protein_coding

tolerated(0.31)

probably_damaging(1)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

QARS

SNV

Missense_Mutation

c.494T>G

p.Ile165Ser

p.I165S

P47897

protein_coding

deleterious(0)

possibly_damaging(0.841)

TCGA-AO-A03P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

QARS

SNV

Missense_Mutation

c.1885N>T

p.Arg629Cys

p.R629C

P47897

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-AR-A24H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

QARS

SNV

Missense_Mutation

rs201359259

c.321N>A

p.Phe107Leu

p.F107L

P47897

protein_coding

tolerated(0.08)

possibly_damaging(0.674)

TCGA-GM-A4E0-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

QARS

insertion

Frame_Shift_Ins

rs772343264

c.679_680insG

p.Glu227GlyfsTer4

p.E227Gfs*4

P47897

protein_coding

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

QARS

insertion

Frame_Shift_Ins

novel

c.1696_1697insGAAAGATATTATTTTTAATATCTTTCGTTAAG

p.Pro566ArgfsTer84

p.P566Rfs*84

P47897

protein_coding

TCGA-AO-A0JE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

QARS

SNV

Missense_Mutation

rs370681625

c.1208N>A

p.Arg403Gln

p.R403Q

P47897

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

QARS

SNV

Missense_Mutation

rs766000850

c.460C>T

p.Arg154Trp

p.R154W

P47897

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

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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