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: TOM1

Gene summary for TOM1

Gene summary.

Gene information	Species	Human
	Gene symbol	TOM1
	Gene ID	10043
	Gene name	target of myb1 membrane trafficking protein
	Gene Alias	IMD85
	Cytomap	22q12.3
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	B3KUF5

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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
10043	TOM1	P2T-E	Human	Esophagus	ESCC	1.94e-26	3.99e-01	0.1177
10043	TOM1	P4T-E	Human	Esophagus	ESCC	1.17e-16	4.55e-01	0.1323
10043	TOM1	P5T-E	Human	Esophagus	ESCC	2.97e-04	1.15e-01	0.1327
10043	TOM1	P8T-E	Human	Esophagus	ESCC	1.24e-22	4.10e-01	0.0889
10043	TOM1	P9T-E	Human	Esophagus	ESCC	7.57e-13	2.75e-01	0.1131
10043	TOM1	P10T-E	Human	Esophagus	ESCC	4.74e-26	2.94e-01	0.116
10043	TOM1	P11T-E	Human	Esophagus	ESCC	4.96e-23	9.11e-01	0.1426
10043	TOM1	P12T-E	Human	Esophagus	ESCC	2.01e-25	3.75e-01	0.1122
10043	TOM1	P15T-E	Human	Esophagus	ESCC	6.26e-25	5.37e-01	0.1149
10043	TOM1	P16T-E	Human	Esophagus	ESCC	1.70e-28	4.59e-01	0.1153
10043	TOM1	P17T-E	Human	Esophagus	ESCC	2.01e-13	6.40e-01	0.1278
10043	TOM1	P19T-E	Human	Esophagus	ESCC	1.67e-05	4.00e-01	0.1662
10043	TOM1	P20T-E	Human	Esophagus	ESCC	3.45e-10	3.69e-01	0.1124
10043	TOM1	P21T-E	Human	Esophagus	ESCC	1.43e-31	5.50e-01	0.1617
10043	TOM1	P22T-E	Human	Esophagus	ESCC	4.94e-18	3.54e-01	0.1236
10043	TOM1	P23T-E	Human	Esophagus	ESCC	3.23e-35	8.56e-01	0.108
10043	TOM1	P24T-E	Human	Esophagus	ESCC	1.44e-22	4.13e-01	0.1287
10043	TOM1	P26T-E	Human	Esophagus	ESCC	2.34e-21	4.98e-01	0.1276
10043	TOM1	P27T-E	Human	Esophagus	ESCC	8.64e-30	5.10e-01	0.1055
10043	TOM1	P28T-E	Human	Esophagus	ESCC	4.70e-13	3.28e-01	0.1149

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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

∗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:00073466	Cervix	CC	regulation of mitotic cell cycle	88/2311	457/18723	1.26e-05	2.60e-04	88
GO:00106399	Cervix	CC	negative regulation of organelle organization	68/2311	348/18723	7.40e-05	1.03e-03	68
GO:00457862	Cervix	CC	negative regulation of cell cycle	67/2311	385/18723	2.21e-03	1.59e-02	67
GO:00459302	Cervix	CC	negative regulation of mitotic cell cycle	44/2311	235/18723	3.02e-03	1.99e-02	44
GO:01400143	Cervix	CC	mitotic nuclear division	50/2311	287/18723	7.27e-03	3.91e-02	50
GO:00109482	Cervix	CC	negative regulation of cell cycle process	51/2311	294/18723	7.35e-03	3.94e-02	51
GO:00482851	Cervix	CC	organelle fission	78/2311	488/18723	9.70e-03	4.79e-02	78
GO:0016197	Colorectum	AD	endosomal transport	90/3918	230/18723	1.88e-10	1.73e-08	90
GO:0010639	Colorectum	AD	negative regulation of organelle organization	114/3918	348/18723	1.41e-07	6.49e-06	114
GO:0046777	Colorectum	AD	protein autophosphorylation	74/3918	227/18723	2.48e-05	4.76e-04	74
GO:0033674	Colorectum	AD	positive regulation of kinase activity	131/3918	467/18723	1.28e-04	1.85e-03	131
GO:0045860	Colorectum	AD	positive regulation of protein kinase activity	107/3918	386/18723	8.01e-04	7.92e-03	107
GO:0007346	Colorectum	AD	regulation of mitotic cell cycle	119/3918	457/18723	4.60e-03	3.14e-02	119
GO:0140014	Colorectum	AD	mitotic nuclear division	78/3918	287/18723	6.48e-03	4.05e-02	78
GO:00106391	Colorectum	SER	negative regulation of organelle organization	90/2897	348/18723	3.14e-07	1.69e-05	90
GO:00161971	Colorectum	SER	endosomal transport	61/2897	230/18723	1.03e-05	3.35e-04	61
GO:00161972	Colorectum	MSS	endosomal transport	79/3467	230/18723	7.04e-09	4.39e-07	79
GO:00106392	Colorectum	MSS	negative regulation of organelle organization	102/3467	348/18723	5.36e-07	2.05e-05	102
GO:00336742	Colorectum	MSS	positive regulation of kinase activity	122/3467	467/18723	2.50e-05	5.21e-04	122
GO:00458602	Colorectum	MSS	positive regulation of protein kinase activity	102/3467	386/18723	6.93e-05	1.20e-03	102

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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

TOM1

SNV

Missense_Mutation

rs201539247

c.128N>T

p.Thr43Met

p.T43M

O60784

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A7-A26E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cytoxan

TOM1

SNV

Missense_Mutation

novel

c.5N>G

p.Asp2Gly

p.D2G

O60784

protein_coding

deleterious(0)

possibly_damaging(0.461)

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

TOM1

SNV

Missense_Mutation

c.1163C>T

p.Ala388Val

p.A388V

O60784

protein_coding

deleterious(0.01)

benign(0.234)

TCGA-EW-A1P8-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

fluorouracil

TOM1

insertion

Frame_Shift_Ins

novel

c.566_567insAGGGAAG

p.Asp190GlyfsTer20

p.D190Gfs*20

O60784

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

TOM1

insertion

Frame_Shift_Ins

novel

c.794_795insAAAATTAGCCAGGCGTGGTG

p.Gln266LysfsTer22

p.Q266Kfs*22

O60784

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TOM1

insertion

Frame_Shift_Ins

novel

c.1132_1133insGAGGGTACATTATGGTACTGTGGGCACCC

p.Ala378GlyfsTer17

p.A378Gfs*17

O60784

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TOM1

insertion

Nonsense_Mutation

novel

c.1123_1124insCTTCCCCAGCAGAATCAATGGATAGCGTTTTGACTGTTCTCTAAC

p.Ser375delinsThrSerProAlaGluSerMetAspSerValLeuThrValLeuTerArg

p.S375delinsTSPAESMDSVLTVL*R

O60784

protein_coding

TCGA-AQ-A04J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TOM1

SNV

Missense_Mutation

novel

c.784C>G

p.Arg262Gly

p.R262G

O60784

protein_coding

deleterious(0)

possibly_damaging(0.551)

TCGA-EK-A2R9-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TOM1

SNV

Missense_Mutation

rs371088274

c.505N>A

p.Val169Met

p.V169M

O60784

protein_coding

deleterious(0.05)

possibly_damaging(0.872)

TCGA-EK-A2RL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

taxol

TOM1

SNV

Missense_Mutation

rs371791801

c.283N>A

p.Val95Met

p.V95M

O60784

protein_coding

deleterious(0.03)

probably_damaging(0.993)

TCGA-VS-A958-01

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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