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: YARS

Gene summary for YARS

Gene summary.

Gene information	Species	Human
	Gene symbol	YARS
	Gene ID	8565
	Gene name	tyrosyl-tRNA synthetase 1
	Gene Alias	CMTDIC
	Cytomap	1p35.1
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	A0A0S2Z4R1

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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
8565	YARS	P8T-E	Human	Esophagus	ESCC	3.10e-20	3.03e-01	0.0889
8565	YARS	P9T-E	Human	Esophagus	ESCC	2.03e-18	1.78e-01	0.1131
8565	YARS	P10T-E	Human	Esophagus	ESCC	3.51e-47	8.11e-01	0.116
8565	YARS	P11T-E	Human	Esophagus	ESCC	2.13e-05	4.64e-01	0.1426
8565	YARS	P12T-E	Human	Esophagus	ESCC	7.60e-28	4.69e-01	0.1122
8565	YARS	P15T-E	Human	Esophagus	ESCC	8.07e-21	5.32e-01	0.1149
8565	YARS	P16T-E	Human	Esophagus	ESCC	1.61e-22	4.95e-01	0.1153
8565	YARS	P17T-E	Human	Esophagus	ESCC	2.44e-11	7.18e-01	0.1278
8565	YARS	P19T-E	Human	Esophagus	ESCC	9.32e-04	7.74e-01	0.1662
8565	YARS	P20T-E	Human	Esophagus	ESCC	7.86e-20	4.37e-01	0.1124
8565	YARS	P21T-E	Human	Esophagus	ESCC	9.43e-51	1.13e+00	0.1617
8565	YARS	P22T-E	Human	Esophagus	ESCC	1.56e-17	2.09e-01	0.1236
8565	YARS	P23T-E	Human	Esophagus	ESCC	1.59e-32	9.86e-01	0.108
8565	YARS	P24T-E	Human	Esophagus	ESCC	7.12e-25	6.17e-01	0.1287
8565	YARS	P26T-E	Human	Esophagus	ESCC	7.94e-36	6.69e-01	0.1276
8565	YARS	P27T-E	Human	Esophagus	ESCC	1.41e-22	4.80e-01	0.1055
8565	YARS	P28T-E	Human	Esophagus	ESCC	6.71e-17	3.39e-01	0.1149
8565	YARS	P30T-E	Human	Esophagus	ESCC	4.85e-12	6.87e-01	0.137
8565	YARS	P31T-E	Human	Esophagus	ESCC	1.08e-33	6.77e-01	0.1251
8565	YARS	P32T-E	Human	Esophagus	ESCC	2.36e-54	1.18e+00	0.1666

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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
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:0006418	Colorectum	AD	tRNA aminoacylation for protein translation	19/3918	41/18723	2.37e-04	3.03e-03	19
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: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:00065201	Colorectum	SER	cellular amino acid metabolic process	61/2897	284/18723	4.20e-03	3.41e-02	61
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:00009592	Esophagus	ESCC	mitochondrial RNA metabolic process	39/8552	49/18723	1.20e-06	1.49e-05	39
GO:00346605	Oral cavity	OSCC	ncRNA metabolic process	296/7305	485/18723	2.94e-23	6.65e-21	296
GO:01400533	Oral cavity	OSCC	mitochondrial gene expression	78/7305	108/18723	2.37e-12	9.86e-11	78
GO:00325434	Oral cavity	OSCC	mitochondrial translation	59/7305	76/18723	7.21e-12	2.70e-10	59
GO:00063991	Oral cavity	OSCC	tRNA metabolic process	101/7305	179/18723	1.65e-06	2.15e-05	101
GO:00009591	Oral cavity	OSCC	mitochondrial RNA metabolic process	29/7305	49/18723	3.33e-03	1.42e-02	29
GO:003466011	Oral cavity	LP	ncRNA metabolic process	205/4623	485/18723	6.46e-18	1.09e-15	205
GO:003254313	Oral cavity	LP	mitochondrial translation	43/4623	76/18723	2.85e-09	1.26e-07	43

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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

YARS

SNV

Missense_Mutation

novel

c.967N>T

p.Pro323Ser

p.P323S

P54577

protein_coding

deleterious(0.01)

possibly_damaging(0.615)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

YARS

SNV

Missense_Mutation

c.988N>G

p.Thr330Ala

p.T330A

P54577

protein_coding

tolerated(0.34)

benign(0)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

YARS

SNV

Missense_Mutation

rs752992202

c.973N>T

p.Arg325Trp

p.R325W

P54577

protein_coding

deleterious(0.01)

probably_damaging(0.994)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

YARS

insertion

Frame_Shift_Ins

novel

c.951_952insTCTCAAAA

p.Asn318SerfsTer19

p.N318Sfs*19

P54577

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

YARS

insertion

Frame_Shift_Ins

novel

c.950_951insCCAGCCTGGGCAACAGAGTGAGACTCTAT

p.Asn318GlnfsTer10

p.N318Qfs*10

P54577

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

YARS

insertion

Frame_Shift_Ins

novel

c.1188_1189insAAGAAAAGAAATGATGAGGCCAGGATTG

p.Ala397LysfsTer11

p.A397Kfs*11

P54577

protein_coding

TCGA-A8-A099-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

YARS

SNV

Missense_Mutation

c.1455G>C

p.Lys485Asn

p.K485N

P54577

protein_coding

deleterious(0.03)

probably_damaging(0.923)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

YARS

SNV

Missense_Mutation

novel

c.1417G>A

p.Glu473Lys

p.E473K

P54577

protein_coding

tolerated_low_confidence(0.06)

benign(0.036)

TCGA-UC-A7PG-06

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

YARS

insertion

In_Frame_Ins

novel

c.1490_1491insGATCCTGGG

p.Ile497delinsMetIleLeuGly

p.I497delinsMILG

P54577

protein_coding

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

YARS

SNV

Missense_Mutation

novel

c.79N>A

p.Leu27Met

p.L27M

P54577

protein_coding

tolerated(0.19)

benign(0.063)

TCGA-AA-3870-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

folinic

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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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