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: NOA1

Gene summary for NOA1

Gene summary.

Gene information	Species	Human
	Gene symbol	NOA1
	Gene ID	84273
	Gene name	nitric oxide associated 1
	Gene Alias	C4orf14
	Cytomap	4q12
	Gene Type	protein-coding
	GO ID	GO:0006091
	UniProtAcc	Q8NC60

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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
84273	NOA1	HTA11_1938_2000001011	Human	Colorectum	AD	3.10e-03	3.24e-01	-0.0811
84273	NOA1	HTA11_347_2000001011	Human	Colorectum	AD	1.35e-09	4.02e-01	-0.1954
84273	NOA1	HTA11_1391_2000001011	Human	Colorectum	AD	4.62e-06	4.16e-01	-0.059
84273	NOA1	HTA11_7862_2000001011	Human	Colorectum	AD	1.15e-02	3.95e-01	-0.0179
84273	NOA1	HTA11_866_3004761011	Human	Colorectum	AD	4.47e-05	3.61e-01	0.096
84273	NOA1	HTA11_4255_2000001011	Human	Colorectum	SER	4.35e-02	3.78e-01	0.0446
84273	NOA1	HTA11_7696_3000711011	Human	Colorectum	AD	6.45e-07	2.89e-01	0.0674
84273	NOA1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.34e-17	5.10e-01	0.294
84273	NOA1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.52e-09	4.26e-01	0.3859
84273	NOA1	LZE4T	Human	Esophagus	ESCC	1.57e-02	9.66e-02	0.0811
84273	NOA1	LZE5T	Human	Esophagus	ESCC	1.91e-02	9.66e-02	0.0514
84273	NOA1	LZE24T	Human	Esophagus	ESCC	2.59e-07	1.56e-01	0.0596
84273	NOA1	LZE21T	Human	Esophagus	ESCC	3.79e-02	9.88e-02	0.0655
84273	NOA1	P1T-E	Human	Esophagus	ESCC	1.02e-05	3.55e-01	0.0875
84273	NOA1	P2T-E	Human	Esophagus	ESCC	5.94e-28	5.00e-01	0.1177
84273	NOA1	P4T-E	Human	Esophagus	ESCC	1.97e-18	3.79e-01	0.1323
84273	NOA1	P5T-E	Human	Esophagus	ESCC	6.64e-13	1.30e-01	0.1327
84273	NOA1	P8T-E	Human	Esophagus	ESCC	4.60e-13	2.93e-01	0.0889
84273	NOA1	P9T-E	Human	Esophagus	ESCC	2.46e-14	2.18e-01	0.1131
84273	NOA1	P10T-E	Human	Esophagus	ESCC	6.29e-14	2.08e-01	0.116

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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
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:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0045333	Colorectum	AD	cellular respiration	119/3918	230/18723	3.21e-25	4.02e-22	119
GO:0015980	Colorectum	AD	energy derivation by oxidation of organic compounds	143/3918	318/18723	2.78e-22	2.49e-19	143
GO:0043467	Colorectum	AD	regulation of generation of precursor metabolites and energy	49/3918	130/18723	8.33e-06	1.99e-04	49
GO:0043457	Colorectum	AD	regulation of cellular respiration	20/3918	49/18723	1.23e-03	1.09e-02	20
GO:00453331	Colorectum	SER	cellular respiration	103/2897	230/18723	2.35e-26	3.61e-23	103
GO:00060911	Colorectum	SER	generation of precursor metabolites and energy	168/2897	490/18723	1.39e-25	1.70e-22	168
GO:00159801	Colorectum	SER	energy derivation by oxidation of organic compounds	119/2897	318/18723	5.28e-22	4.62e-19	119
GO:00434671	Colorectum	SER	regulation of generation of precursor metabolites and energy	38/2897	130/18723	4.94e-05	1.21e-03	38
GO:00434571	Colorectum	SER	regulation of cellular respiration	16/2897	49/18723	2.11e-03	2.06e-02	16
GO:00060912	Colorectum	MSS	generation of precursor metabolites and energy	186/3467	490/18723	1.14e-24	2.15e-21	186
GO:00453332	Colorectum	MSS	cellular respiration	107/3467	230/18723	1.64e-22	2.05e-19	107
GO:00159802	Colorectum	MSS	energy derivation by oxidation of organic compounds	131/3467	318/18723	2.60e-21	2.70e-18	131
GO:00434672	Colorectum	MSS	regulation of generation of precursor metabolites and energy	47/3467	130/18723	1.47e-06	4.85e-05	47
GO:00434572	Colorectum	MSS	regulation of cellular respiration	19/3467	49/18723	7.20e-04	7.70e-03	19
GO:0006091110	Esophagus	ESCC	generation of precursor metabolites and energy	331/8552	490/18723	3.86e-23	8.45e-21	331
GO:0045333110	Esophagus	ESCC	cellular respiration	173/8552	230/18723	4.53e-20	5.99e-18	173
GO:014005313	Esophagus	ESCC	mitochondrial gene expression	93/8552	108/18723	1.96e-18	2.03e-16	93
GO:0015980110	Esophagus	ESCC	energy derivation by oxidation of organic compounds	220/8552	318/18723	1.20e-17	1.09e-15	220
GO:003254314	Esophagus	ESCC	mitochondrial translation	68/8552	76/18723	1.02e-15	6.86e-14	68

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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

NOA1

SNV

Missense_Mutation

rs772975026

c.1630C>T

p.Arg544Cys

p.R544C

Q8NC60

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NOA1

SNV

Missense_Mutation

novel

c.1420A>G

p.Thr474Ala

p.T474A

Q8NC60

protein_coding

tolerated(1)

benign(0.001)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NOA1

SNV

Missense_Mutation

rs150082024

c.1931N>A

p.Arg644Gln

p.R644Q

Q8NC60

protein_coding

deleterious(0.03)

probably_damaging(0.965)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NOA1

SNV

Missense_Mutation

c.1007N>A

p.Arg336His

p.R336H

Q8NC60

protein_coding

deleterious(0)

probably_damaging(0.945)

TCGA-AO-A0J3-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

NOA1

SNV

Missense_Mutation

c.976G>A

p.Glu326Lys

p.E326K

Q8NC60

protein_coding

tolerated(0.22)

possibly_damaging(0.467)

TCGA-BH-A1EN-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NOA1

SNV

Missense_Mutation

novel

c.163G>C

p.Asp55His

p.D55H

Q8NC60

protein_coding

tolerated_low_confidence(0.07)

benign(0.137)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NOA1

insertion

Nonsense_Mutation

novel

c.1310-1_1310insACTCAGTTCTGATTCATTCATGAAAGCTGTTTAGGGGTGAAT

p.Gly437delinsAspSerValLeuIleHisSerTerLysLeuPheArgGlyGluTer

p.G437delinsDSVLIHS*KLFRGE*

Q8NC60

protein_coding

TCGA-A8-A07P-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

NOA1

insertion

Frame_Shift_Ins

novel

c.1146_1147insGGAA

p.Thr383GlyfsTer21

p.T383Gfs*21

Q8NC60

protein_coding

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NOA1

insertion

In_Frame_Ins

novel

c.1145_1146insCCCTTTAGCGATAAGGCTACTGTT

p.Gly382_Thr383insProLeuAlaIleArgLeuLeuPhe

p.G382_T383insPLAIRLLF

Q8NC60

protein_coding

TCGA-B6-A0I5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NOA1

deletion

Frame_Shift_Del

novel

c.1720delN

p.Ala574GlnfsTer37

p.A574Qfs*37

Q8NC60

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

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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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