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: YTHDC1

Gene summary for YTHDC1

Gene summary.

Gene information	Species	Human
	Gene symbol	YTHDC1
	Gene ID	91746
	Gene name	YTH domain containing 1
	Gene Alias	YT521
	Cytomap	4q13.2
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q96MU7

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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
91746	YTHDC1	LZE4T	Human	Esophagus	ESCC	1.17e-23	6.48e-01	0.0811
91746	YTHDC1	LZE7T	Human	Esophagus	ESCC	9.51e-07	7.92e-01	0.0667
91746	YTHDC1	LZE8T	Human	Esophagus	ESCC	1.52e-12	3.57e-01	0.067
91746	YTHDC1	LZE20T	Human	Esophagus	ESCC	5.53e-06	5.02e-01	0.0662
91746	YTHDC1	LZE24T	Human	Esophagus	ESCC	1.74e-14	5.77e-01	0.0596
91746	YTHDC1	LZE21T	Human	Esophagus	ESCC	1.38e-05	7.44e-01	0.0655
91746	YTHDC1	LZE6T	Human	Esophagus	ESCC	5.29e-10	1.41e-01	0.0845
91746	YTHDC1	P1T-E	Human	Esophagus	ESCC	1.68e-17	9.90e-01	0.0875
91746	YTHDC1	P2T-E	Human	Esophagus	ESCC	1.05e-51	9.08e-01	0.1177
91746	YTHDC1	P4T-E	Human	Esophagus	ESCC	1.20e-28	8.49e-01	0.1323
91746	YTHDC1	P5T-E	Human	Esophagus	ESCC	1.18e-21	4.85e-01	0.1327
91746	YTHDC1	P8T-E	Human	Esophagus	ESCC	3.82e-44	7.93e-01	0.0889
91746	YTHDC1	P9T-E	Human	Esophagus	ESCC	4.11e-14	5.30e-01	0.1131
91746	YTHDC1	P10T-E	Human	Esophagus	ESCC	2.53e-39	8.01e-01	0.116
91746	YTHDC1	P11T-E	Human	Esophagus	ESCC	2.08e-12	8.46e-01	0.1426
91746	YTHDC1	P12T-E	Human	Esophagus	ESCC	5.35e-40	7.66e-01	0.1122
91746	YTHDC1	P15T-E	Human	Esophagus	ESCC	2.21e-31	8.24e-01	0.1149
91746	YTHDC1	P16T-E	Human	Esophagus	ESCC	1.66e-40	7.08e-01	0.1153
91746	YTHDC1	P17T-E	Human	Esophagus	ESCC	3.48e-09	6.15e-01	0.1278
91746	YTHDC1	P19T-E	Human	Esophagus	ESCC	4.16e-07	6.50e-01	0.1662

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:000838033	Oral cavity	NEOLP	RNA splicing	110/2005	434/18723	2.29e-18	2.72e-15	110
GO:004802433	Oral cavity	NEOLP	regulation of mRNA splicing, via spliceosome	44/2005	101/18723	2.43e-17	2.06e-14	44
GO:000037733	Oral cavity	NEOLP	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	81/2005	320/18723	7.96e-14	2.63e-11	81
GO:000039833	Oral cavity	NEOLP	mRNA splicing, via spliceosome	81/2005	320/18723	7.96e-14	2.63e-11	81
GO:000037533	Oral cavity	NEOLP	RNA splicing, via transesterification reactions	81/2005	324/18723	1.64e-13	5.13e-11	81
GO:000691331	Oral cavity	NEOLP	nucleocytoplasmic transport	75/2005	301/18723	1.56e-12	3.20e-10	75
GO:005116931	Oral cavity	NEOLP	nuclear transport	75/2005	301/18723	1.56e-12	3.20e-10	75
GO:007182634	Oral cavity	NEOLP	ribonucleoprotein complex subunit organization	60/2005	227/18723	1.98e-11	2.81e-09	60
GO:000038031	Oral cavity	NEOLP	alternative mRNA splicing, via spliceosome	30/2005	77/18723	8.63e-11	9.32e-09	30
GO:002261834	Oral cavity	NEOLP	ribonucleoprotein complex assembly	57/2005	220/18723	1.46e-10	1.43e-08	57
GO:002261333	Oral cavity	NEOLP	ribonucleoprotein complex biogenesis	93/2005	463/18723	1.34e-09	9.49e-08	93
GO:000038132	Oral cavity	NEOLP	regulation of alternative mRNA splicing, via spliceosome	24/2005	60/18723	3.51e-09	2.04e-07	24
GO:000640331	Oral cavity	NEOLP	RNA localization	50/2005	201/18723	8.49e-09	4.39e-07	50
GO:000170132	Oral cavity	NEOLP	in utero embryonic development	76/2005	367/18723	1.11e-08	5.44e-07	76
GO:005116832	Oral cavity	NEOLP	nuclear export	41/2005	154/18723	2.35e-08	1.03e-06	41
GO:005065731	Oral cavity	NEOLP	nucleic acid transport	40/2005	163/18723	3.74e-07	1.15e-05	40
GO:005065831	Oral cavity	NEOLP	RNA transport	40/2005	163/18723	3.74e-07	1.15e-05	40
GO:005123631	Oral cavity	NEOLP	establishment of RNA localization	40/2005	166/18723	6.24e-07	1.82e-05	40
GO:001593131	Oral cavity	NEOLP	nucleobase-containing compound transport	48/2005	222/18723	1.51e-06	3.77e-05	48
GO:005102831	Oral cavity	NEOLP	mRNA transport	31/2005	130/18723	1.38e-05	2.43e-04	31

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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

YTHDC1

SNV

Missense_Mutation

novel

c.1038N>A

p.Ser346Arg

p.S346R

protein_coding

tolerated(0.3)

benign(0.157)

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

YTHDC1

SNV

Missense_Mutation

c.485N>A

p.Arg162His

p.R162H

protein_coding

tolerated_low_confidence(0.08)

benign(0.361)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

YTHDC1

SNV

Missense_Mutation

c.937N>T

p.Asp313Tyr

p.D313Y

protein_coding

deleterious(0)

probably_damaging(0.947)

TCGA-AQ-A1H2-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

herceptin

YTHDC1

SNV

Missense_Mutation

rs766073192

c.561N>G

p.Ser187Arg

p.S187R

protein_coding

deleterious_low_confidence(0)

benign(0.191)

TCGA-AQ-A1H3-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

YTHDC1

SNV

Missense_Mutation

c.92A>G

p.Tyr31Cys

p.Y31C

protein_coding

tolerated_low_confidence(0.26)

probably_damaging(0.996)

TCGA-AR-A2LQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

YTHDC1

SNV

Missense_Mutation

c.1165N>A

p.Leu389Ile

p.L389I

protein_coding

deleterious(0.05)

benign(0.174)

TCGA-D8-A1JG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

YTHDC1

SNV

Missense_Mutation

rs756562328

c.2044N>T

p.Arg682Trp

p.R682W

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.649)

TCGA-E2-A1LA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

YTHDC1

SNV

Missense_Mutation

novel

c.713A>T

p.Glu238Val

p.E238V

protein_coding

tolerated_low_confidence(0.08)

benign(0.006)

TCGA-E9-A243-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

YTHDC1

insertion

Nonsense_Mutation

novel

c.260_261insCCAATTCTCTGATGTTTAAAGA

p.Lys88GlnfsTer6

p.K88Qfs*6

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

YTHDC1

SNV

Missense_Mutation

novel

c.280G>A

p.Glu94Lys

p.E94K

protein_coding

deleterious_low_confidence(0.01)

benign(0.051)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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