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: IARS

Gene summary for IARS

Gene summary.

Gene information	Species	Human
	Gene symbol	IARS
	Gene ID	3376
	Gene name	isoleucyl-tRNA synthetase 1
	Gene Alias	GRIDHH
	Cytomap	9q22.31
	Gene Type	protein-coding
	GO ID	GO:0001503
	UniProtAcc	P41252

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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
3376	IARS	CCI_1	Human	Cervix	CC	2.31e-12	5.29e-01	0.528
3376	IARS	CCI_2	Human	Cervix	CC	2.27e-22	1.01e+00	0.5249
3376	IARS	CCI_3	Human	Cervix	CC	1.09e-21	6.82e-01	0.516
3376	IARS	CCII_1	Human	Cervix	CC	9.25e-04	1.62e-01	0.3249
3376	IARS	Tumor	Human	Cervix	CC	8.49e-22	3.48e-01	0.1241
3376	IARS	sample3	Human	Cervix	CC	1.78e-27	4.05e-01	0.1387
3376	IARS	H2	Human	Cervix	HSIL_HPV	4.00e-05	1.67e-01	0.0632
3376	IARS	T1	Human	Cervix	CC	2.20e-03	1.24e-01	0.0918
3376	IARS	T2	Human	Cervix	CC	8.72e-04	1.78e-01	0.0709
3376	IARS	T3	Human	Cervix	CC	7.90e-34	4.62e-01	0.1389
3376	IARS	HTA11_3410_2000001011	Human	Colorectum	AD	3.12e-20	-5.02e-01	0.0155
3376	IARS	HTA11_2487_2000001011	Human	Colorectum	SER	1.15e-11	-5.02e-01	-0.1808
3376	IARS	HTA11_1938_2000001011	Human	Colorectum	AD	1.20e-08	-5.02e-01	-0.0811
3376	IARS	HTA11_78_2000001011	Human	Colorectum	AD	6.98e-14	-5.02e-01	-0.1088
3376	IARS	HTA11_347_2000001011	Human	Colorectum	AD	8.95e-22	-5.02e-01	-0.1954
3376	IARS	HTA11_3361_2000001011	Human	Colorectum	AD	5.14e-09	-5.02e-01	-0.1207
3376	IARS	HTA11_83_2000001011	Human	Colorectum	SER	5.03e-07	-5.02e-01	-0.1526
3376	IARS	HTA11_696_2000001011	Human	Colorectum	AD	3.49e-32	-5.02e-01	-0.1464
3376	IARS	HTA11_866_2000001011	Human	Colorectum	AD	2.12e-29	-5.02e-01	-0.1001
3376	IARS	HTA11_1391_2000001011	Human	Colorectum	AD	2.93e-16	-5.02e-01	-0.059

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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:0006418	Colorectum	AD	tRNA aminoacylation for protein translation	19/3918	41/18723	2.37e-04	3.03e-03	19
GO:0001649	Colorectum	AD	osteoblast differentiation	70/3918	229/18723	3.59e-04	4.18e-03	70
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:0001503	Colorectum	AD	ossification	106/3918	408/18723	7.68e-03	4.64e-02	106
GO:00064181	Colorectum	SER	tRNA aminoacylation for protein translation	17/2897	41/18723	5.75e-05	1.35e-03	17
GO:00430391	Colorectum	SER	tRNA aminoacylation	17/2897	44/18723	1.64e-04	3.12e-03	17
GO:00430381	Colorectum	SER	amino acid activation	17/2897	45/18723	2.25e-04	3.91e-03	17
GO:00016491	Colorectum	SER	osteoblast differentiation	56/2897	229/18723	2.49e-04	4.21e-03	56
GO:00065201	Colorectum	SER	cellular amino acid metabolic process	61/2897	284/18723	4.20e-03	3.41e-02	61
GO:00015031	Colorectum	SER	ossification	82/2897	408/18723	6.76e-03	4.78e-02	82
GO:003466012	Esophagus	ESCC	ncRNA metabolic process	346/8552	485/18723	4.35e-31	2.51e-28	346
GO:014005313	Esophagus	ESCC	mitochondrial gene expression	93/8552	108/18723	1.96e-18	2.03e-16	93
GO:003254314	Esophagus	ESCC	mitochondrial translation	68/8552	76/18723	1.02e-15	6.86e-14	68
GO:00063992	Esophagus	ESCC	tRNA metabolic process	122/8552	179/18723	9.03e-10	2.19e-08	122
GO:00346603	Liver	Cirrhotic	ncRNA metabolic process	173/4634	485/18723	3.64e-08	1.21e-06	173
GO:0032543	Liver	Cirrhotic	mitochondrial translation	40/4634	76/18723	1.61e-07	4.29e-06	40
GO:0140053	Liver	Cirrhotic	mitochondrial gene expression	49/4634	108/18723	2.35e-06	4.31e-05	49
GO:000652011	Liver	Cirrhotic	cellular amino acid metabolic process	103/4634	284/18723	8.88e-06	1.30e-04	103

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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

IARS

SNV

Missense_Mutation

c.712G>A

p.Val238Ile

p.V238I

P41252

protein_coding

deleterious(0.02)

probably_damaging(0.919)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

IARS

SNV

Missense_Mutation

c.1143N>C

p.Leu381Phe

p.L381F

P41252

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

IARS

SNV

Missense_Mutation

c.2864C>G

p.Thr955Arg

p.T955R

P41252

protein_coding

tolerated(0.44)

benign(0)

TCGA-AO-A03P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

IARS

SNV

Missense_Mutation

c.3661N>G

p.Arg1221Gly

p.R1221G

P41252

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.721)

TCGA-B6-A1KN-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

IARS

SNV

Missense_Mutation

rs367830465

c.2423N>A

p.Arg808His

p.R808H

P41252

protein_coding

tolerated(0.14)

benign(0)

TCGA-BH-A18N-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IARS

SNV

Missense_Mutation

c.3282A>T

p.Gln1094His

p.Q1094H

P41252

protein_coding

tolerated(0.11)

benign(0.001)

TCGA-C8-A132-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

IARS

SNV

Missense_Mutation

novel

c.2329A>G

p.Thr777Ala

p.T777A

P41252

protein_coding

tolerated(0.13)

benign(0.196)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

IARS

insertion

Nonsense_Mutation

novel

c.3345_3346insTGCTGCAAATTTTTGTGATTTCCTGTCTCCATATTCCAGAATTTAT

p.Ser1116CysfsTer6

p.S1116Cfs*6

P41252

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IARS

insertion

Nonsense_Mutation

novel

c.782_783insTATCAAATAAT

p.Arg262IlefsTer3

p.R262Ifs*3

P41252

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IARS

insertion

Frame_Shift_Ins

novel

c.3184_3185insT

p.Gly1062ValfsTer3

p.G1062Vfs*3

P41252

protein_coding

TCGA-B6-A0IM-01

Breast

breast invasive carcinoma

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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