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: TMCO1

Gene summary for TMCO1

Gene summary.

Gene information	Species	Human
	Gene symbol	TMCO1
	Gene ID	54499
	Gene name	transmembrane and coiled-coil domains 1
	Gene Alias	HP10122
	Cytomap	1q24.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	B7Z591

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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
54499	TMCO1	GSM4909282	Human	Breast	IDC	1.71e-15	5.65e-01	-0.0288
54499	TMCO1	GSM4909285	Human	Breast	IDC	9.23e-07	3.51e-01	0.21
54499	TMCO1	GSM4909286	Human	Breast	IDC	1.11e-05	-2.72e-01	0.1081
54499	TMCO1	GSM4909287	Human	Breast	IDC	7.29e-06	3.18e-01	0.2057
54499	TMCO1	GSM4909293	Human	Breast	IDC	4.92e-27	6.24e-01	0.1581
54499	TMCO1	GSM4909294	Human	Breast	IDC	6.89e-03	-1.18e-01	0.2022
54499	TMCO1	GSM4909296	Human	Breast	IDC	5.64e-12	-6.74e-02	0.1524
54499	TMCO1	GSM4909297	Human	Breast	IDC	4.08e-16	-1.47e-01	0.1517
54499	TMCO1	GSM4909298	Human	Breast	IDC	1.37e-07	4.17e-01	0.1551
54499	TMCO1	GSM4909301	Human	Breast	IDC	2.19e-100	1.17e+00	0.1577
54499	TMCO1	GSM4909302	Human	Breast	IDC	3.70e-06	3.34e-01	0.1545
54499	TMCO1	GSM4909306	Human	Breast	IDC	4.08e-21	5.83e-01	0.1564
54499	TMCO1	GSM4909307	Human	Breast	IDC	5.54e-15	5.24e-01	0.1569
54499	TMCO1	GSM4909308	Human	Breast	IDC	2.64e-31	6.78e-01	0.158
54499	TMCO1	GSM4909309	Human	Breast	IDC	1.65e-03	2.28e-01	0.0483
54499	TMCO1	GSM4909311	Human	Breast	IDC	1.51e-30	-5.23e-02	0.1534
54499	TMCO1	GSM4909312	Human	Breast	IDC	1.71e-13	3.04e-01	0.1552
54499	TMCO1	GSM4909313	Human	Breast	IDC	1.61e-09	3.87e-01	0.0391
54499	TMCO1	GSM4909317	Human	Breast	IDC	6.85e-36	7.78e-01	0.1355
54499	TMCO1	GSM4909318	Human	Breast	IDC	9.32e-04	3.41e-01	0.2031

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:00349769	Breast	Precancer	response to endoplasmic reticulum stress	38/1080	256/18723	7.89e-08	4.60e-06	38
GO:00712167	Breast	Precancer	cellular response to biotic stimulus	28/1080	246/18723	4.67e-04	6.14e-03	28
GO:00324697	Breast	Precancer	endoplasmic reticulum calcium ion homeostasis	6/1080	25/18723	2.49e-03	2.28e-02	6
GO:00069845	Breast	Precancer	ER-nucleus signaling pathway	8/1080	46/18723	4.40e-03	3.43e-02	8
GO:0072503	Breast	Precancer	cellular divalent inorganic cation homeostasis	42/1080	486/18723	5.91e-03	4.21e-02	42
GO:003497614	Breast	IDC	response to endoplasmic reticulum stress	43/1434	256/18723	8.42e-07	3.82e-05	43
GO:003246913	Breast	IDC	endoplasmic reticulum calcium ion homeostasis	8/1434	25/18723	3.85e-04	5.40e-03	8
GO:000698412	Breast	IDC	ER-nucleus signaling pathway	10/1434	46/18723	2.15e-03	2.00e-02	10
GO:007121611	Breast	IDC	cellular response to biotic stimulus	31/1434	246/18723	4.23e-03	3.31e-02	31
GO:003497622	Breast	DCIS	response to endoplasmic reticulum stress	43/1390	256/18723	3.65e-07	1.71e-05	43
GO:000698421	Breast	DCIS	ER-nucleus signaling pathway	10/1390	46/18723	1.70e-03	1.68e-02	10
GO:003246922	Breast	DCIS	endoplasmic reticulum calcium ion homeostasis	7/1390	25/18723	1.79e-03	1.73e-02	7
GO:007121621	Breast	DCIS	cellular response to biotic stimulus	30/1390	246/18723	4.99e-03	3.72e-02	30
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90
GO:0032469	Colorectum	AD	endoplasmic reticulum calcium ion homeostasis	16/3918	25/18723	3.80e-06	1.04e-04	16
GO:0006984	Colorectum	AD	ER-nucleus signaling pathway	21/3918	46/18723	1.47e-04	2.08e-03	21
GO:00349762	Colorectum	MSS	response to endoplasmic reticulum stress	81/3467	256/18723	2.65e-07	1.10e-05	81
GO:00324692	Colorectum	MSS	endoplasmic reticulum calcium ion homeostasis	16/3467	25/18723	6.86e-07	2.48e-05	16
GO:00069842	Colorectum	MSS	ER-nucleus signaling pathway	19/3467	46/18723	2.79e-04	3.69e-03	19
GO:0006983	Colorectum	MSS	ER overload response	7/3467	13/18723	4.46e-03	3.15e-02	7

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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

TMCO1

SNV

Missense_Mutation

c.354G>C

p.Lys118Asn

p.K118N

protein_coding

deleterious(0)

possibly_damaging(0.881)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMCO1

SNV

Missense_Mutation

novel

c.143N>A

p.Arg48Gln

p.R48Q

protein_coding

deleterious_low_confidence(0.03)

benign(0.034)

TCGA-BH-A0HB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

TMCO1

SNV

Missense_Mutation

c.442T>A

p.Cys148Ser

p.C148S

protein_coding

tolerated(0.34)

benign(0.006)

TCGA-D8-A146-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMCO1

SNV

Missense_Mutation

c.410N>C

p.Val137Ala

p.V137A

protein_coding

tolerated(0.19)

possibly_damaging(0.469)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

TMCO1

SNV

Missense_Mutation

c.332N>T

p.Ser111Leu

p.S111L

protein_coding

tolerated(0.11)

possibly_damaging(0.861)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TMCO1

SNV

Missense_Mutation

rs763875549

c.413G>A

p.Arg138Gln

p.R138Q

protein_coding

deleterious(0.01)

possibly_damaging(0.591)

TCGA-AA-3510-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TMCO1

SNV

Missense_Mutation

c.236T>A

p.Val79Asp

p.V79D

protein_coding

deleterious(0)

possibly_damaging(0.889)

TCGA-DM-A1HB-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

TMCO1

SNV

Missense_Mutation

novel

c.586N>G

p.Phe196Val

p.F196V

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TMCO1

SNV

Missense_Mutation

novel

c.527T>C

p.Ile176Thr

p.I176T

protein_coding

deleterious(0.03)

benign(0.041)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

TMCO1

SNV

Missense_Mutation

rs763875549

c.413G>A

p.Arg138Gln

p.R138Q

protein_coding

deleterious(0.01)

possibly_damaging(0.591)

TCGA-AP-A056-01

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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