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: TMEM98

Gene summary for TMEM98

Gene summary.

Gene information	Species	Human
	Gene symbol	TMEM98
	Gene ID	26022
	Gene name	transmembrane protein 98
	Gene Alias	TADA1
	Cytomap	17q11.2
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q9Y2Y6

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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
26022	TMEM98	P22T-E	Human	Esophagus	ESCC	6.67e-59	9.48e-01	0.1236
26022	TMEM98	P24T-E	Human	Esophagus	ESCC	1.85e-02	1.35e-01	0.1287
26022	TMEM98	P26T-E	Human	Esophagus	ESCC	2.27e-25	5.20e-01	0.1276
26022	TMEM98	P27T-E	Human	Esophagus	ESCC	2.88e-18	5.22e-01	0.1055
26022	TMEM98	P28T-E	Human	Esophagus	ESCC	3.36e-11	1.47e-01	0.1149
26022	TMEM98	P30T-E	Human	Esophagus	ESCC	2.58e-34	1.15e+00	0.137
26022	TMEM98	P31T-E	Human	Esophagus	ESCC	2.14e-12	3.77e-01	0.1251
26022	TMEM98	P32T-E	Human	Esophagus	ESCC	2.22e-22	6.02e-01	0.1666
26022	TMEM98	P36T-E	Human	Esophagus	ESCC	2.66e-12	4.66e-01	0.1187
26022	TMEM98	P37T-E	Human	Esophagus	ESCC	3.02e-19	4.65e-01	0.1371
26022	TMEM98	P40T-E	Human	Esophagus	ESCC	3.56e-14	3.49e-01	0.109
26022	TMEM98	P42T-E	Human	Esophagus	ESCC	4.70e-25	6.51e-01	0.1175
26022	TMEM98	P44T-E	Human	Esophagus	ESCC	7.29e-10	5.26e-01	0.1096
26022	TMEM98	P47T-E	Human	Esophagus	ESCC	1.02e-10	4.56e-01	0.1067
26022	TMEM98	P48T-E	Human	Esophagus	ESCC	1.82e-04	2.80e-01	0.0959
26022	TMEM98	P49T-E	Human	Esophagus	ESCC	7.21e-03	6.39e-01	0.1768
26022	TMEM98	P52T-E	Human	Esophagus	ESCC	1.47e-11	5.03e-01	0.1555
26022	TMEM98	P56T-E	Human	Esophagus	ESCC	3.09e-14	1.80e+00	0.1613
26022	TMEM98	P57T-E	Human	Esophagus	ESCC	8.98e-33	7.52e-01	0.0926
26022	TMEM98	P61T-E	Human	Esophagus	ESCC	7.86e-15	6.48e-01	0.099

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:1900180	Colorectum	AD	regulation of protein localization to nucleus	55/3918	136/18723	1.70e-07	7.34e-06	55
GO:0034504	Colorectum	AD	protein localization to nucleus	94/3918	290/18723	2.83e-06	8.09e-05	94
GO:0045861	Colorectum	AD	negative regulation of proteolysis	106/3918	351/18723	2.33e-05	4.57e-04	106
GO:0051604	Colorectum	AD	protein maturation	85/3918	294/18723	6.73e-04	6.91e-03	85
GO:1903828	Colorectum	AD	negative regulation of cellular protein localization	39/3918	117/18723	1.18e-03	1.06e-02	39
GO:0050767	Colorectum	AD	regulation of neurogenesis	99/3918	364/18723	2.35e-03	1.82e-02	99
GO:0016485	Colorectum	AD	protein processing	63/3918	225/18723	6.77e-03	4.19e-02	63
GO:19001801	Colorectum	SER	regulation of protein localization to nucleus	46/2897	136/18723	8.50e-08	5.27e-06	46
GO:00458611	Colorectum	SER	negative regulation of proteolysis	88/2897	351/18723	1.74e-06	7.50e-05	88
GO:00345041	Colorectum	SER	protein localization to nucleus	74/2897	290/18723	5.74e-06	2.05e-04	74
GO:00516041	Colorectum	SER	protein maturation	73/2897	294/18723	1.82e-05	5.38e-04	73
GO:00164851	Colorectum	SER	protein processing	55/2897	225/18723	2.84e-04	4.67e-03	55
GO:19038281	Colorectum	SER	negative regulation of cellular protein localization	30/2897	117/18723	2.96e-03	2.62e-02	30
GO:19001802	Colorectum	MSS	regulation of protein localization to nucleus	54/3467	136/18723	6.20e-09	3.95e-07	54
GO:00345042	Colorectum	MSS	protein localization to nucleus	92/3467	290/18723	3.66e-08	1.98e-06	92
GO:00458612	Colorectum	MSS	negative regulation of proteolysis	97/3467	351/18723	1.57e-05	3.54e-04	97
GO:00507671	Colorectum	MSS	regulation of neurogenesis	94/3467	364/18723	3.12e-04	4.06e-03	94
GO:19038282	Colorectum	MSS	negative regulation of cellular protein localization	36/3467	117/18723	9.19e-04	9.34e-03	36
GO:00516042	Colorectum	MSS	protein maturation	75/3467	294/18723	1.70e-03	1.53e-02	75
GO:0050768	Colorectum	MSS	negative regulation of neurogenesis	39/3467	140/18723	4.30e-03	3.07e-02	39

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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

TMEM98

SNV

Missense_Mutation

novel

c.176N>A

p.Pro59His

p.P59H

Q9Y2Y6

protein_coding

tolerated(0.12)

benign(0.232)

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMEM98

insertion

Nonsense_Mutation

novel

c.610_611insGCTTCAGTTAACTATGTTTAA

p.Ala204delinsGlyPheSerTerLeuCysLeuThr

p.A204delinsGFS*LCLT

Q9Y2Y6

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMEM98

insertion

Frame_Shift_Ins

novel

c.535_536insAATCCAACAATCCCACTCCTTGGTATTTATCCAAA

p.Leu179GlnfsTer13

p.L179Qfs*13

Q9Y2Y6

protein_coding

TCGA-AN-A0XW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TMEM98

SNV

Missense_Mutation

c.196N>A

p.Asp66Asn

p.D66N

Q9Y2Y6

protein_coding

tolerated(0.07)

benign(0.094)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TMEM98

SNV

Missense_Mutation

c.506N>C

p.Leu169Pro

p.L169P

Q9Y2Y6

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AA-3815-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TMEM98

SNV

Missense_Mutation

novel

c.578N>A

p.Ala193Asp

p.A193D

Q9Y2Y6

protein_coding

deleterious(0.01)

possibly_damaging(0.675)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

TMEM98

SNV

Missense_Mutation

novel

c.268N>A

p.Leu90Ile

p.L90I

Q9Y2Y6

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TMEM98

SNV

Missense_Mutation

rs753209256

c.379N>A

p.Asp127Asn

p.D127N

Q9Y2Y6

protein_coding

deleterious(0.03)

possibly_damaging(0.555)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TMEM98

SNV

Missense_Mutation

c.544N>A

p.Gly182Ser

p.G182S

Q9Y2Y6

protein_coding

tolerated(1)

benign(0)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMEM98

SNV

Missense_Mutation

novel

c.254N>G

p.Glu85Gly

p.E85G

Q9Y2Y6

protein_coding

tolerated(0.18)

benign(0.266)

TCGA-AX-A2H2-01

Endometrium

uterine corpus endometrioid 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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