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: YTHDF1

Gene summary for YTHDF1

Gene summary.

Gene information	Species	Human
	Gene symbol	YTHDF1
	Gene ID	54915
	Gene name	YTH N6-methyladenosine RNA binding protein 1
	Gene Alias	C20orf21
	Cytomap	20q13.33
	Gene Type	protein-coding
	GO ID	GO:0000902
	UniProtAcc	Q9BYJ9

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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
54915	YTHDF1	S027	Human	Liver	HCC	6.02e-06	6.38e-01	0.2446
54915	YTHDF1	S028	Human	Liver	HCC	1.34e-19	8.38e-01	0.2503
54915	YTHDF1	S029	Human	Liver	HCC	1.68e-12	6.23e-01	0.2581
54915	YTHDF1	C04	Human	Oral cavity	OSCC	1.20e-04	3.38e-01	0.2633
54915	YTHDF1	C21	Human	Oral cavity	OSCC	6.12e-26	8.05e-01	0.2678
54915	YTHDF1	C30	Human	Oral cavity	OSCC	2.35e-34	1.42e+00	0.3055
54915	YTHDF1	C43	Human	Oral cavity	OSCC	1.23e-03	1.73e-01	0.1704
54915	YTHDF1	C51	Human	Oral cavity	OSCC	1.71e-08	5.26e-01	0.2674
54915	YTHDF1	C57	Human	Oral cavity	OSCC	2.19e-05	2.54e-01	0.1679
54915	YTHDF1	C06	Human	Oral cavity	OSCC	1.12e-03	5.69e-01	0.2699
54915	YTHDF1	C08	Human	Oral cavity	OSCC	2.16e-18	4.61e-01	0.1919
54915	YTHDF1	C09	Human	Oral cavity	OSCC	4.97e-06	3.62e-01	0.1431
54915	YTHDF1	LN46	Human	Oral cavity	OSCC	1.22e-06	3.33e-01	0.1666
54915	YTHDF1	SYSMH1	Human	Oral cavity	OSCC	2.47e-09	3.56e-01	0.1127
54915	YTHDF1	SYSMH2	Human	Oral cavity	OSCC	1.39e-11	3.39e-01	0.2326
54915	YTHDF1	SYSMH3	Human	Oral cavity	OSCC	3.36e-16	4.44e-01	0.2442
54915	YTHDF1	SYSMH5	Human	Oral cavity	OSCC	5.64e-05	2.00e-01	0.0647
54915	YTHDF1	SYSMH6	Human	Oral cavity	OSCC	9.38e-04	1.81e-01	0.1275
54915	YTHDF1	P4_S8_cSCC	Human	Skin	cSCC	6.44e-03	1.43e-01	-0.3095
54915	YTHDF1	P5_S10_cSCC	Human	Skin	cSCC	3.84e-03	9.65e-02	-0.299

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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

∗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:0009896111	Esophagus	ESCC	positive regulation of catabolic process	332/8552	492/18723	4.36e-23	9.22e-21	332
GO:0031331111	Esophagus	ESCC	positive regulation of cellular catabolic process	292/8552	427/18723	8.67e-22	1.53e-19	292
GO:1903311110	Esophagus	ESCC	regulation of mRNA metabolic process	210/8552	288/18723	3.25e-21	5.56e-19	210
GO:0006401110	Esophagus	ESCC	RNA catabolic process	204/8552	278/18723	3.39e-21	5.66e-19	204
GO:0006413110	Esophagus	ESCC	translational initiation	100/8552	118/18723	1.16e-18	1.25e-16	100
GO:0034655110	Esophagus	ESCC	nucleobase-containing compound catabolic process	272/8552	407/18723	2.92e-18	2.90e-16	272
GO:0006402110	Esophagus	ESCC	mRNA catabolic process	170/8552	232/18723	8.70e-18	8.00e-16	170
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304
GO:004670018	Esophagus	ESCC	heterocycle catabolic process	286/8552	445/18723	1.12e-15	7.47e-14	286
GO:0045727111	Esophagus	ESCC	positive regulation of translation	107/8552	136/18723	2.79e-15	1.68e-13	107
GO:004427019	Esophagus	ESCC	cellular nitrogen compound catabolic process	288/8552	451/18723	3.03e-15	1.79e-13	288
GO:0034250111	Esophagus	ESCC	positive regulation of cellular amide metabolic process	123/8552	162/18723	3.32e-15	1.93e-13	123
GO:001943918	Esophagus	ESCC	aromatic compound catabolic process	295/8552	467/18723	1.09e-14	5.98e-13	295
GO:190136118	Esophagus	ESCC	organic cyclic compound catabolic process	307/8552	495/18723	9.99e-14	4.80e-12	307
GO:000644617	Esophagus	ESCC	regulation of translational initiation	65/8552	79/18723	2.04e-11	7.07e-10	65
GO:190331316	Esophagus	ESCC	positive regulation of mRNA metabolic process	87/8552	118/18723	5.10e-10	1.32e-08	87
GO:006101319	Esophagus	ESCC	regulation of mRNA catabolic process	115/8552	166/18723	5.90e-10	1.49e-08	115
GO:004348719	Esophagus	ESCC	regulation of RNA stability	117/8552	170/18723	7.91e-10	1.94e-08	117
GO:004348819	Esophagus	ESCC	regulation of mRNA stability	109/8552	158/18723	2.40e-09	5.35e-08	109
GO:006101416	Esophagus	ESCC	positive regulation of mRNA catabolic process	63/8552	87/18723	3.70e-07	5.15e-06	63

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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

YTHDF1

SNV

Missense_Mutation

c.75G>C

p.Gln25His

p.Q25H

Q9BYJ9

protein_coding

deleterious(0.03)

probably_damaging(0.94)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

YTHDF1

SNV

Missense_Mutation

novel

c.1399N>A

p.Gln467Lys

p.Q467K

Q9BYJ9

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

YTHDF1

SNV

Missense_Mutation

c.385N>C

p.Phe129Leu

p.F129L

Q9BYJ9

protein_coding

deleterious(0)

possibly_damaging(0.828)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

YTHDF1

SNV

Missense_Mutation

c.737C>A

p.Pro246His

p.P246H

Q9BYJ9

protein_coding

deleterious(0.04)

possibly_damaging(0.873)

TCGA-D8-A1XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin+cyclophosphamide

YTHDF1

SNV

Missense_Mutation

c.1351N>A

p.Glu451Lys

p.E451K

Q9BYJ9

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

YTHDF1

SNV

Missense_Mutation

novel

c.431N>A

p.Ser144Asn

p.S144N

Q9BYJ9

protein_coding

tolerated(0.13)

benign(0.011)

TCGA-D8-A3Z6-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphane

YTHDF1

insertion

Frame_Shift_Ins

novel

c.486_487insCCGAAGG

p.Val163ProfsTer4

p.V163Pfs*4

Q9BYJ9

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

YTHDF1

insertion

In_Frame_Ins

novel

c.484_485insACATTGGCACCTGGGATAACAAGGGGCCTG

p.Thr161_Val162insAspIleGlyThrTrpAspAsnLysGlyPro

p.T161_V162insDIGTWDNKGP

Q9BYJ9

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

YTHDF1

insertion

In_Frame_Ins

novel

c.1408_1409insCCTGGGTTGATACATTTTTTGGTTTTA

p.Trp470delinsSerTrpValAspThrPhePheGlyPheArg

p.W470delinsSWVDTFFGFR

Q9BYJ9

protein_coding

TCGA-A8-A09D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

YTHDF1

insertion

Frame_Shift_Ins

novel

c.1400_1401insCTTTCTCCTCTCCTTTTTGAATTGTGATACTTTCTGGAAC

p.Gln467HisfsTer22

p.Q467Hfs*22

Q9BYJ9

protein_coding

TCGA-AN-A0FN-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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