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: TOM1L1

Gene summary for TOM1L1

Gene summary.

Gene information	Species	Human
	Gene symbol	TOM1L1
	Gene ID	10040
	Gene name	target of myb1 like 1 membrane trafficking protein
	Gene Alias	SRCASM
	Cytomap	17q22
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	O75674

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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
10040	TOM1L1	HTA11_866_3004761011	Human	Colorectum	AD	5.61e-04	-3.41e-01	0.096
10040	TOM1L1	HTA11_7696_3000711011	Human	Colorectum	AD	3.11e-06	-3.11e-01	0.0674
10040	TOM1L1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.46e-04	-2.97e-01	0.3859
10040	TOM1L1	HTA11_99999974143_84620	Human	Colorectum	MSS	2.79e-08	-3.18e-01	0.3005
10040	TOM1L1	F007	Human	Colorectum	FAP	6.40e-03	-2.59e-01	0.1176
10040	TOM1L1	A001-C-207	Human	Colorectum	FAP	1.20e-07	-3.92e-01	0.1278
10040	TOM1L1	A015-C-203	Human	Colorectum	FAP	1.68e-22	-4.26e-01	-0.1294
10040	TOM1L1	A015-C-204	Human	Colorectum	FAP	4.31e-11	-4.07e-01	-0.0228
10040	TOM1L1	A014-C-040	Human	Colorectum	FAP	6.92e-05	-4.40e-01	-0.1184
10040	TOM1L1	A002-C-201	Human	Colorectum	FAP	3.64e-15	-3.88e-01	0.0324
10040	TOM1L1	A002-C-203	Human	Colorectum	FAP	6.24e-07	-2.57e-01	0.2786
10040	TOM1L1	A001-C-119	Human	Colorectum	FAP	8.92e-07	-4.28e-01	-0.1557
10040	TOM1L1	A001-C-108	Human	Colorectum	FAP	2.96e-18	-3.83e-01	-0.0272
10040	TOM1L1	A002-C-205	Human	Colorectum	FAP	2.68e-23	-4.99e-01	-0.1236
10040	TOM1L1	A001-C-104	Human	Colorectum	FAP	4.46e-08	-3.15e-01	0.0184
10040	TOM1L1	A015-C-005	Human	Colorectum	FAP	5.31e-04	-2.13e-01	-0.0336
10040	TOM1L1	A015-C-006	Human	Colorectum	FAP	7.79e-13	-3.80e-01	-0.0994
10040	TOM1L1	A015-C-106	Human	Colorectum	FAP	2.75e-17	-3.55e-01	-0.0511
10040	TOM1L1	A002-C-114	Human	Colorectum	FAP	1.90e-18	-4.80e-01	-0.1561
10040	TOM1L1	A015-C-104	Human	Colorectum	FAP	2.65e-26	-4.60e-01	-0.1899

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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
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:00431621	Liver	HCC	ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	17/7958	23/18723	2.28e-03	1.13e-02	17
GO:0051784	Liver	HCC	negative regulation of nuclear division	34/7958	56/18723	4.54e-03	1.96e-02	34
GO:00321471	Liver	HCC	activation of protein kinase activity	72/7958	134/18723	5.61e-03	2.33e-02	72
GO:01400145	Oral cavity	OSCC	mitotic nuclear division	191/7305	287/18723	1.99e-21	3.70e-19	191
GO:00073469	Oral cavity	OSCC	regulation of mitotic cell cycle	266/7305	457/18723	3.87e-17	3.41e-15	266
GO:00482852	Oral cavity	OSCC	organelle fission	265/7305	488/18723	3.22e-12	1.27e-10	265
GO:00002801	Oral cavity	OSCC	nuclear division	237/7305	439/18723	9.62e-11	2.90e-09	237
GO:001063918	Oral cavity	OSCC	negative regulation of organelle organization	190/7305	348/18723	2.12e-09	4.97e-08	190
GO:00457864	Oral cavity	OSCC	negative regulation of cell cycle	206/7305	385/18723	4.28e-09	9.55e-08	206
GO:00459304	Oral cavity	OSCC	negative regulation of mitotic cell cycle	132/7305	235/18723	6.51e-08	1.16e-06	132
GO:00070882	Oral cavity	OSCC	regulation of mitotic nuclear division	68/7305	110/18723	1.05e-06	1.41e-05	68
GO:00109483	Oral cavity	OSCC	negative regulation of cell cycle process	155/7305	294/18723	1.11e-06	1.48e-05	155
GO:00467779	Oral cavity	OSCC	protein autophosphorylation	123/7305	227/18723	2.31e-06	2.93e-05	123
GO:004586016	Oral cavity	OSCC	positive regulation of protein kinase activity	194/7305	386/18723	3.90e-06	4.59e-05	194
GO:003367418	Oral cavity	OSCC	positive regulation of kinase activity	228/7305	467/18723	8.31e-06	8.90e-05	228
GO:0051783	Oral cavity	OSCC	regulation of nuclear division	78/7305	139/18723	3.13e-05	2.86e-04	78
GO:00458392	Oral cavity	OSCC	negative regulation of mitotic nuclear division	32/7305	48/18723	9.60e-05	7.25e-04	32
GO:00431622	Oral cavity	OSCC	ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	17/7305	23/18723	7.28e-04	3.98e-03	17
GO:00517842	Oral cavity	OSCC	negative regulation of nuclear division	34/7305	56/18723	8.17e-04	4.35e-03	34
GO:0031952	Oral cavity	OSCC	regulation of protein autophosphorylation	27/7305	43/18723	1.35e-03	6.62e-03	27

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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

TOM1L1

SNV

Missense_Mutation

c.592N>T

p.Val198Phe

p.V198F

O75674

protein_coding

deleterious(0)

probably_damaging(0.961)

TCGA-AR-A24H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

TOM1L1

SNV

Missense_Mutation

novel

c.1231N>G

p.Thr411Ala

p.T411A

O75674

protein_coding

tolerated(0.34)

benign(0.003)

TCGA-JL-A3YW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TOM1L1

insertion

Frame_Shift_Ins

novel

c.564_565insAGCTTAAGAATTGTGTTTTCGGCTGGGTGCGGTG

p.Ala189SerfsTer31

p.A189Sfs*31

O75674

protein_coding

TCGA-A8-A07U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

TOM1L1

deletion

Frame_Shift_Del

novel

c.970delN

p.Arg325GlyfsTer13

p.R325Gfs*13

O75674

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TOM1L1

SNV

Missense_Mutation

novel

c.1122N>T

p.Glu374Asp

p.E374D

O75674

protein_coding

tolerated(0.07)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TOM1L1

SNV

Missense_Mutation

c.1095N>C

p.Met365Ile

p.M365I

O75674

protein_coding

tolerated(0.09)

benign(0.01)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

TOM1L1

SNV

Missense_Mutation

c.820G>A

p.Glu274Lys

p.E274K

O75674

protein_coding

tolerated(0.08)

probably_damaging(0.969)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

TOM1L1

SNV

Missense_Mutation

novel

c.439G>T

p.Val147Phe

p.V147F

O75674

protein_coding

tolerated(0.09)

benign(0.026)

TCGA-VS-A9U6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TOM1L1

SNV

Missense_Mutation

c.286N>A

p.Phe96Ile

p.F96I

O75674

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TOM1L1

SNV

Missense_Mutation

novel

c.366N>A

p.Phe122Leu

p.F122L

O75674

protein_coding

tolerated(0.74)

benign(0.141)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<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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