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: MICU1

Gene summary for MICU1

Gene summary.

Gene information	Species	Human
	Gene symbol	MICU1
	Gene ID	10367
	Gene name	mitochondrial calcium uptake 1
	Gene Alias	CALC
	Cytomap	10q22.1
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q9BPX6

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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
10367	MICU1	HTA11_3410_2000001011	Human	Colorectum	AD	1.70e-08	-2.47e-01	0.0155
10367	MICU1	HTA11_411_2000001011	Human	Colorectum	SER	2.84e-02	5.79e-01	-0.2602
10367	MICU1	HTA11_5212_2000001011	Human	Colorectum	AD	2.74e-02	-2.93e-01	-0.2061
10367	MICU1	HTA11_99999974143_84620	Human	Colorectum	MSS	6.28e-11	-4.82e-01	0.3005
10367	MICU1	A001-C-207	Human	Colorectum	FAP	2.32e-02	-1.87e-01	0.1278
10367	MICU1	A015-C-203	Human	Colorectum	FAP	2.32e-21	-3.39e-01	-0.1294
10367	MICU1	A015-C-204	Human	Colorectum	FAP	1.72e-06	-3.08e-01	-0.0228
10367	MICU1	A014-C-040	Human	Colorectum	FAP	3.96e-05	-2.56e-01	-0.1184
10367	MICU1	A002-C-201	Human	Colorectum	FAP	1.60e-11	-3.20e-01	0.0324
10367	MICU1	A002-C-203	Human	Colorectum	FAP	5.09e-03	-1.56e-01	0.2786
10367	MICU1	A001-C-119	Human	Colorectum	FAP	1.29e-04	-1.41e-01	-0.1557
10367	MICU1	A001-C-108	Human	Colorectum	FAP	9.89e-14	-2.22e-01	-0.0272
10367	MICU1	A002-C-205	Human	Colorectum	FAP	1.63e-19	-2.74e-01	-0.1236
10367	MICU1	A015-C-005	Human	Colorectum	FAP	1.31e-02	-1.37e-01	-0.0336
10367	MICU1	A015-C-006	Human	Colorectum	FAP	1.36e-14	-3.40e-01	-0.0994
10367	MICU1	A015-C-106	Human	Colorectum	FAP	6.73e-09	-2.19e-01	-0.0511
10367	MICU1	A002-C-114	Human	Colorectum	FAP	9.92e-18	-3.48e-01	-0.1561
10367	MICU1	A015-C-104	Human	Colorectum	FAP	1.68e-24	-2.16e-01	-0.1899
10367	MICU1	A001-C-014	Human	Colorectum	FAP	2.39e-14	-2.74e-01	0.0135
10367	MICU1	A002-C-016	Human	Colorectum	FAP	1.57e-20	-3.53e-01	0.0521

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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
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
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:00512592	Esophagus	ESCC	protein complex oligomerization	130/8552	238/18723	3.29e-03	1.36e-02	130
GO:00714724	Esophagus	ESCC	cellular response to salt stress	10/8552	12/18723	8.94e-03	3.12e-02	10
GO:00712145	Liver	NAFLD	cellular response to abiotic stimulus	56/1882	331/18723	7.01e-05	1.47e-03	56
GO:01040045	Liver	NAFLD	cellular response to environmental stimulus	56/1882	331/18723	7.01e-05	1.47e-03	56
GO:00069703	Liver	NAFLD	response to osmotic stress	20/1882	84/18723	1.95e-04	3.41e-03	20
GO:00621977	Liver	NAFLD	cellular response to chemical stress	54/1882	337/18723	3.83e-04	5.73e-03	54
GO:00515613	Liver	NAFLD	positive regulation of mitochondrial calcium ion concentration	5/1882	11/18723	2.81e-03	2.55e-02	5
GO:00515605	Liver	NAFLD	mitochondrial calcium ion homeostasis	8/1882	26/18723	3.06e-03	2.75e-02	8
GO:006219712	Liver	Cirrhotic	cellular response to chemical stress	147/4634	337/18723	1.84e-14	1.72e-12	147
GO:00068397	Liver	Cirrhotic	mitochondrial transport	112/4634	254/18723	1.03e-11	6.66e-10	112
GO:007121411	Liver	Cirrhotic	cellular response to abiotic stimulus	115/4634	331/18723	2.62e-05	3.38e-04	115
GO:010400411	Liver	Cirrhotic	cellular response to environmental stimulus	115/4634	331/18723	2.62e-05	3.38e-04	115
GO:005156011	Liver	Cirrhotic	mitochondrial calcium ion homeostasis	15/4634	26/18723	3.43e-04	2.93e-03	15
GO:19905425	Liver	Cirrhotic	mitochondrial transmembrane transport	41/4634	102/18723	4.08e-04	3.37e-03	41
GO:000697011	Liver	Cirrhotic	response to osmotic stress	34/4634	84/18723	1.06e-03	7.40e-03	34
GO:005156111	Liver	Cirrhotic	positive regulation of mitochondrial calcium ion concentration	8/4634	11/18723	1.10e-03	7.64e-03	8
GO:00364444	Liver	Cirrhotic	calcium import into the mitochondrion	8/4634	14/18723	9.65e-03	4.35e-02	8
GO:000683912	Liver	HCC	mitochondrial transport	184/7958	254/18723	2.30e-22	3.83e-20	184
GO:006219722	Liver	HCC	cellular response to chemical stress	216/7958	337/18723	6.86e-16	5.44e-14	216
GO:199054212	Liver	HCC	mitochondrial transmembrane transport	78/7958	102/18723	2.73e-12	1.26e-10	78

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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

MICU1

SNV

Missense_Mutation

novel

c.395N>A

p.Ala132Asp

p.A132D

Q9BPX6

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

MICU1

SNV

Missense_Mutation

novel

c.218N>C

p.Lys73Thr

p.K73T

Q9BPX6

protein_coding

tolerated_low_confidence(0.12)

benign(0.001)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MICU1

SNV

Missense_Mutation

rs754124319

c.523C>T

p.Arg175Cys

p.R175C

Q9BPX6

protein_coding

deleterious(0)

probably_damaging(0.917)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

MICU1

SNV

Missense_Mutation

c.232G>C

p.Asp78His

p.D78H

Q9BPX6

protein_coding

deleterious(0.03)

benign(0)

TCGA-EW-A6SD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

tch

MICU1

SNV

Missense_Mutation

novel

c.23N>T

p.Ser8Phe

p.S8F

Q9BPX6

protein_coding

deleterious_low_confidence(0.03)

benign(0.365)

TCGA-PE-A5DC-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

MICU1

deletion

Frame_Shift_Del

novel

c.721delN

p.Glu241LysfsTer47

p.E241Kfs*47

Q9BPX6

protein_coding

TCGA-BH-A1EN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MICU1

SNV

Missense_Mutation

rs367648335

c.775C>T

p.Arg259Cys

p.R259C

Q9BPX6

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-VS-A9UI-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

MICU1

SNV

Missense_Mutation

rs752729268

c.524N>A

p.Arg175His

p.R175H

Q9BPX6

protein_coding

deleterious(0.04)

benign(0.072)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

MICU1

SNV

Missense_Mutation

c.451N>T

p.Asp151Tyr

p.D151Y

Q9BPX6

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AZ-4616-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

MICU1

SNV

Missense_Mutation

rs750157034

c.776N>A

p.Arg259His

p.R259H

Q9BPX6

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-AZ-6601-01

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
10367	MICU1	TRANSPORTER		ALD-403	EPTINEZUMAB
10367	MICU1	TRANSPORTER		PF-4427429

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