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: SCO1

Gene summary for SCO1

Gene summary.

Gene information	Species	Human
	Gene symbol	SCO1
	Gene ID	6341
	Gene name	synthesis of cytochrome C oxidase 1
	Gene Alias	MC4DN4
	Cytomap	17p13.1
	Gene Type	protein-coding
	GO ID	GO:0006873
	UniProtAcc	O75880

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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
6341	SCO1	HTA11_347_2000001011	Human	Colorectum	AD	1.16e-10	3.28e-01	-0.1954
6341	SCO1	HTA11_1391_2000001011	Human	Colorectum	AD	1.76e-02	1.75e-01	-0.059
6341	SCO1	HTA11_10623_2000001011	Human	Colorectum	AD	1.51e-03	3.92e-01	-0.0177
6341	SCO1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.06e-07	3.92e-01	0.294
6341	SCO1	A015-C-203	Human	Colorectum	FAP	1.21e-02	-8.63e-02	-0.1294
6341	SCO1	LZE2T	Human	Esophagus	ESCC	1.53e-05	6.06e-01	0.082
6341	SCO1	LZE4T	Human	Esophagus	ESCC	1.69e-09	2.15e-01	0.0811
6341	SCO1	LZE7T	Human	Esophagus	ESCC	1.01e-14	4.30e-01	0.0667
6341	SCO1	LZE20T	Human	Esophagus	ESCC	3.83e-04	1.51e-01	0.0662
6341	SCO1	LZE24T	Human	Esophagus	ESCC	6.79e-12	3.57e-01	0.0596
6341	SCO1	LZE6T	Human	Esophagus	ESCC	3.23e-03	1.58e-01	0.0845
6341	SCO1	P1T-E	Human	Esophagus	ESCC	1.54e-06	3.69e-01	0.0875
6341	SCO1	P2T-E	Human	Esophagus	ESCC	3.27e-17	3.56e-01	0.1177
6341	SCO1	P4T-E	Human	Esophagus	ESCC	3.50e-21	5.74e-01	0.1323
6341	SCO1	P5T-E	Human	Esophagus	ESCC	2.58e-17	3.08e-01	0.1327
6341	SCO1	P8T-E	Human	Esophagus	ESCC	1.99e-16	3.64e-01	0.0889
6341	SCO1	P9T-E	Human	Esophagus	ESCC	1.29e-13	3.10e-01	0.1131
6341	SCO1	P10T-E	Human	Esophagus	ESCC	1.77e-18	3.58e-01	0.116
6341	SCO1	P11T-E	Human	Esophagus	ESCC	1.56e-14	5.04e-01	0.1426
6341	SCO1	P12T-E	Human	Esophagus	ESCC	1.80e-21	4.14e-01	0.1122

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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:0033108	Colorectum	AD	mitochondrial respiratory chain complex assembly	46/3918	93/18723	8.95e-10	6.91e-08	46
GO:0055076	Colorectum	AD	transition metal ion homeostasis	53/3918	138/18723	1.89e-06	5.65e-05	53
GO:0046916	Colorectum	AD	cellular transition metal ion homeostasis	43/3918	115/18723	3.62e-05	6.56e-04	43
GO:00331082	Colorectum	MSS	mitochondrial respiratory chain complex assembly	44/3467	93/18723	2.17e-10	2.09e-08	44
GO:00550762	Colorectum	MSS	transition metal ion homeostasis	45/3467	138/18723	4.99e-05	9.02e-04	45
GO:00469162	Colorectum	MSS	cellular transition metal ion homeostasis	35/3467	115/18723	1.33e-03	1.26e-02	35
GO:00550764	Colorectum	FAP	transition metal ion homeostasis	33/2622	138/18723	1.22e-03	1.14e-02	33
GO:00008194	Esophagus	ESCC	sister chromatid segregation	157/8552	202/18723	8.41e-21	1.33e-18	157
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:0033108110	Esophagus	ESCC	mitochondrial respiratory chain complex assembly	83/8552	93/18723	9.56e-19	1.05e-16	83
GO:000705911	Esophagus	ESCC	chromosome segregation	238/8552	346/18723	1.72e-18	1.82e-16	238
GO:00062604	Esophagus	ESCC	DNA replication	181/8552	260/18723	3.55e-15	2.05e-13	181
GO:001839413	Esophagus	ESCC	peptidyl-lysine acetylation	123/8552	169/18723	6.58e-13	2.94e-11	123
GO:00988133	Esophagus	ESCC	nuclear chromosome segregation	187/8552	281/18723	1.00e-12	4.36e-11	187
GO:004354313	Esophagus	ESCC	protein acylation	165/8552	243/18723	1.69e-12	7.14e-11	165
GO:000647313	Esophagus	ESCC	protein acetylation	140/8552	201/18723	4.37e-12	1.69e-10	140
GO:001700413	Esophagus	ESCC	cytochrome complex assembly	34/8552	36/18723	5.08e-10	1.31e-08	34
GO:000853512	Esophagus	ESCC	respiratory chain complex IV assembly	24/8552	26/18723	6.87e-07	8.99e-06	24
GO:003361712	Esophagus	ESCC	mitochondrial cytochrome c oxidase assembly	21/8552	22/18723	8.75e-07	1.13e-05	21
GO:00062754	Esophagus	ESCC	regulation of DNA replication	73/8552	107/18723	1.97e-06	2.28e-05	73

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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

SCO1

SNV

Missense_Mutation

novel

c.742N>T

p.Gly248Cys

p.G248C

O75880

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SCO1

SNV

Missense_Mutation

c.73C>G

p.Arg25Gly

p.R25G

O75880

protein_coding

deleterious_low_confidence(0.01)

benign(0.07)

TCGA-FU-A23K-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

SCO1

SNV

Missense_Mutation

rs776887702

c.100G>A

p.Glu34Lys

p.E34K

O75880

protein_coding

tolerated_low_confidence(0.27)

benign(0)

TCGA-Q1-A6DT-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

SCO1

SNV

Missense_Mutation

c.616N>A

p.Glu206Lys

p.E206K

O75880

protein_coding

deleterious(0)

possibly_damaging(0.763)

TCGA-AA-3952-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

SCO1

SNV

Missense_Mutation

novel

c.358N>A

p.Ala120Thr

p.A120T

O75880

protein_coding

tolerated(0.58)

benign(0.003)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

SCO1

SNV

Missense_Mutation

novel

c.626N>T

p.Thr209Ile

p.T209I

O75880

protein_coding

deleterious(0.03)

possibly_damaging(0.724)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

SCO1

SNV

Missense_Mutation

novel

c.244G>A

p.Gly82Arg

p.G82R

O75880

protein_coding

tolerated(0.68)

benign(0)

TCGA-AJ-A3OJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

SCO1

SNV

Missense_Mutation

rs145764824

c.640N>A

p.Ala214Thr

p.A214T

O75880

protein_coding

deleterious(0.01)

possibly_damaging(0.861)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SCO1

SNV

Missense_Mutation

novel

c.11T>A

p.Leu4Gln

p.L4Q

O75880

protein_coding

deleterious_low_confidence(0.01)

benign(0.083)

TCGA-B5-A11P-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SCO1

SNV

Missense_Mutation

rs774730754

c.620G>A

p.Arg207Lys

p.R207K

O75880

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B5-A3FC-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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