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: AGO3

Gene summary for AGO3

Gene summary.

Gene information	Species	Human
	Gene symbol	AGO3
	Gene ID	192669
	Gene name	argonaute RISC catalytic component 3
	Gene Alias	EIF2C3
	Cytomap	1p34.3
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	B4E1P5

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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
192669	AGO3	CA_HPV_1	Human	Cervix	CC	1.40e-02	-6.35e-02	0.0264
192669	AGO3	CCI_1	Human	Cervix	CC	1.95e-02	4.52e-01	0.528
192669	AGO3	CCI_2	Human	Cervix	CC	3.13e-05	6.07e-01	0.5249
192669	AGO3	CCI_3	Human	Cervix	CC	2.36e-06	6.09e-01	0.516
192669	AGO3	HTA11_3410_2000001011	Human	Colorectum	AD	5.66e-07	-4.03e-01	0.0155
192669	AGO3	HTA11_3361_2000001011	Human	Colorectum	AD	3.08e-02	-4.29e-01	-0.1207
192669	AGO3	HTA11_696_2000001011	Human	Colorectum	AD	1.51e-02	-2.60e-01	-0.1464
192669	AGO3	HTA11_866_2000001011	Human	Colorectum	AD	2.26e-02	-2.99e-01	-0.1001
192669	AGO3	HTA11_866_3004761011	Human	Colorectum	AD	1.33e-05	-3.37e-01	0.096
192669	AGO3	HTA11_6818_2000001021	Human	Colorectum	AD	4.27e-04	-4.39e-01	0.0588
192669	AGO3	HTA11_99999970781_79442	Human	Colorectum	MSS	3.72e-07	-3.47e-01	0.294
192669	AGO3	HTA11_99999974143_84620	Human	Colorectum	MSS	2.46e-08	-3.52e-01	0.3005
192669	AGO3	A002-C-010	Human	Colorectum	FAP	3.44e-02	-1.32e-01	0.242
192669	AGO3	A001-C-207	Human	Colorectum	FAP	3.35e-07	-3.88e-01	0.1278
192669	AGO3	A015-C-203	Human	Colorectum	FAP	1.94e-29	-4.25e-01	-0.1294
192669	AGO3	A015-C-204	Human	Colorectum	FAP	5.79e-06	-3.13e-01	-0.0228
192669	AGO3	A014-C-040	Human	Colorectum	FAP	2.37e-04	-4.67e-01	-0.1184
192669	AGO3	A002-C-201	Human	Colorectum	FAP	2.88e-14	-3.64e-01	0.0324
192669	AGO3	A002-C-203	Human	Colorectum	FAP	5.36e-03	-2.10e-01	0.2786
192669	AGO3	A001-C-119	Human	Colorectum	FAP	1.62e-07	-3.70e-01	-0.1557

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00064029	Cervix	CC	mRNA catabolic process	56/2311	232/18723	4.81e-07	1.83e-05	56
GO:00064019	Cervix	CC	RNA catabolic process	62/2311	278/18723	2.18e-06	6.56e-05	62
GO:000641710	Cervix	CC	regulation of translation	89/2311	468/18723	1.86e-05	3.46e-04	89
GO:002261310	Cervix	CC	ribonucleoprotein complex biogenesis	88/2311	463/18723	2.11e-05	3.82e-04	88
GO:002261810	Cervix	CC	ribonucleoprotein complex assembly	49/2311	220/18723	2.52e-05	4.29e-04	49
GO:007182610	Cervix	CC	ribonucleoprotein complex subunit organization	49/2311	227/18723	5.91e-05	8.54e-04	49
GO:00467008	Cervix	CC	heterocycle catabolic process	80/2311	445/18723	3.23e-04	3.42e-03	80
GO:00346559	Cervix	CC	nucleobase-containing compound catabolic process	74/2311	407/18723	3.77e-04	3.88e-03	74
GO:00442709	Cervix	CC	cellular nitrogen compound catabolic process	79/2311	451/18723	7.80e-04	6.91e-03	79
GO:00194398	Cervix	CC	aromatic compound catabolic process	79/2311	467/18723	2.14e-03	1.54e-02	79
GO:19013618	Cervix	CC	organic cyclic compound catabolic process	80/2311	495/18723	6.77e-03	3.72e-02	80
GO:00351966	Cervix	CC	production of miRNAs involved in gene silencing by miRNA	13/2311	52/18723	9.09e-03	4.60e-02	13
GO:0022618	Colorectum	AD	ribonucleoprotein complex assembly	92/3918	220/18723	1.49e-12	2.60e-10	92
GO:0071826	Colorectum	AD	ribonucleoprotein complex subunit organization	94/3918	227/18723	1.70e-12	2.87e-10	94
GO:0006401	Colorectum	AD	RNA catabolic process	102/3918	278/18723	8.64e-10	6.76e-08	102
GO:0022613	Colorectum	AD	ribonucleoprotein complex biogenesis	151/3918	463/18723	1.96e-09	1.39e-07	151
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0006402	Colorectum	AD	mRNA catabolic process	87/3918	232/18723	4.40e-09	2.84e-07	87
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133

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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

AGO3

SNV

Missense_Mutation

c.59N>T

p.Arg20Ile

p.R20I

Q9H9G7

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-A7-A0DA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

AGO3

SNV

Missense_Mutation

novel

c.868N>T

p.Ala290Ser

p.A290S

Q9H9G7

protein_coding

tolerated(0.1)

possibly_damaging(0.562)

TCGA-A7-A13F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

AGO3

SNV

Missense_Mutation

c.1207C>T

p.Arg403Trp

p.R403W

Q9H9G7

protein_coding

deleterious(0)

possibly_damaging(0.462)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AGO3

SNV

Missense_Mutation

c.1396G>C

p.Glu466Gln

p.E466Q

Q9H9G7

protein_coding

tolerated(0.33)

benign(0.001)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

AGO3

SNV

Missense_Mutation

c.2507N>T

p.Asn836Ile

p.N836I

Q9H9G7

protein_coding

tolerated(0.19)

benign(0.129)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

AGO3

SNV

Missense_Mutation

c.2423A>G

p.His808Arg

p.H808R

Q9H9G7

protein_coding

tolerated(0.08)

benign(0.424)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

AGO3

insertion

Frame_Shift_Ins

novel

c.1985_1986insCTCCTGCCTCAGCT

p.Thr663SerfsTer29

p.T663Sfs*29

Q9H9G7

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AGO3

deletion

Frame_Shift_Del

c.269_273delNNNNN

p.Arg90ThrfsTer47

p.R90Tfs*47

Q9H9G7

protein_coding

TCGA-BH-A0BW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

AGO3

SNV

Missense_Mutation

novel

c.722T>C

p.Ile241Thr

p.I241T

Q9H9G7

protein_coding

tolerated(0.1)

benign(0.047)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AGO3

SNV

Missense_Mutation

c.1820G>A

p.Gly607Glu

p.G607E

Q9H9G7

protein_coding

tolerated(0.15)

benign(0.012)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

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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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