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: SMG1

Gene summary for SMG1

Gene summary.

Gene information	Species	Human
	Gene symbol	SMG1
	Gene ID	23049
	Gene name	SMG1 nonsense mediated mRNA decay associated PI3K related kinase
	Gene Alias	61E3.4
	Cytomap	16p12.3
	Gene Type	protein-coding
	GO ID	GO:0000184
	UniProtAcc	Q96Q15

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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
23049	SMG1	CA_HPV_1	Human	Cervix	CC	6.90e-07	1.84e-01	0.0264
23049	SMG1	CCI_2	Human	Cervix	CC	5.93e-14	1.40e+00	0.5249
23049	SMG1	CCI_3	Human	Cervix	CC	7.78e-07	8.77e-01	0.516
23049	SMG1	HTA11_3410_2000001011	Human	Colorectum	AD	5.34e-19	-7.29e-01	0.0155
23049	SMG1	HTA11_2487_2000001011	Human	Colorectum	SER	7.99e-05	-4.43e-01	-0.1808
23049	SMG1	HTA11_3361_2000001011	Human	Colorectum	AD	3.80e-03	-5.47e-01	-0.1207
23049	SMG1	HTA11_696_2000001011	Human	Colorectum	AD	1.73e-09	-3.82e-01	-0.1464
23049	SMG1	HTA11_866_2000001011	Human	Colorectum	AD	1.09e-02	-3.12e-01	-0.1001
23049	SMG1	HTA11_5212_2000001011	Human	Colorectum	AD	5.80e-03	-6.25e-01	-0.2061
23049	SMG1	HTA11_9341_2000001011	Human	Colorectum	SER	2.68e-02	-8.29e-01	-0.00410000000000005
23049	SMG1	HTA11_866_3004761011	Human	Colorectum	AD	1.23e-10	-6.40e-01	0.096
23049	SMG1	HTA11_8622_2000001021	Human	Colorectum	SER	1.86e-06	-8.79e-01	0.0528
23049	SMG1	HTA11_10711_2000001011	Human	Colorectum	AD	5.36e-03	-4.39e-01	0.0338
23049	SMG1	HTA11_7696_3000711011	Human	Colorectum	AD	1.00e-22	-6.37e-01	0.0674
23049	SMG1	HTA11_11156_2000001011	Human	Colorectum	AD	2.62e-03	-1.04e+00	0.0397
23049	SMG1	HTA11_6818_2000001021	Human	Colorectum	AD	4.05e-09	-6.25e-01	0.0588
23049	SMG1	HTA11_99999970781_79442	Human	Colorectum	MSS	2.00e-14	-4.25e-01	0.294
23049	SMG1	HTA11_99999971662_82457	Human	Colorectum	MSS	5.36e-08	-3.68e-01	0.3859
23049	SMG1	HTA11_99999974143_84620	Human	Colorectum	MSS	5.32e-32	-6.88e-01	0.3005
23049	SMG1	F007	Human	Colorectum	FAP	2.94e-02	-2.93e-01	0.1176

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:00069139	Cervix	CC	nucleocytoplasmic transport	71/2311	301/18723	4.04e-08	2.54e-06	71
GO:00511699	Cervix	CC	nuclear transport	71/2311	301/18723	4.04e-08	2.54e-06	71
GO:003133010	Cervix	CC	negative regulation of cellular catabolic process	63/2311	262/18723	1.10e-07	5.68e-06	63
GO:00064029	Cervix	CC	mRNA catabolic process	56/2311	232/18723	4.81e-07	1.83e-05	56
GO:000989510	Cervix	CC	negative regulation of catabolic process	69/2311	320/18723	2.15e-06	6.55e-05	69
GO:00064019	Cervix	CC	RNA catabolic process	62/2311	278/18723	2.18e-06	6.56e-05	62
GO:00511689	Cervix	CC	nuclear export	38/2311	154/18723	1.86e-05	3.46e-04	38
GO:00009567	Cervix	CC	nuclear-transcribed mRNA catabolic process	30/2311	112/18723	2.60e-05	4.37e-04	30
GO:00512368	Cervix	CC	establishment of RNA localization	39/2311	166/18723	4.76e-05	7.25e-04	39
GO:00181057	Cervix	CC	peptidyl-serine phosphorylation	63/2311	315/18723	6.65e-05	9.47e-04	63
GO:00506578	Cervix	CC	nucleic acid transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:00506588	Cervix	CC	RNA transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:00182096	Cervix	CC	peptidyl-serine modification	66/2311	338/18723	9.58e-05	1.25e-03	66
GO:00162367	Cervix	CC	macroautophagy	58/2311	291/18723	1.40e-04	1.70e-03	58
GO:20010209	Cervix	CC	regulation of response to DNA damage stimulus	46/2311	219/18723	1.92e-04	2.23e-03	46
GO:000640310	Cervix	CC	RNA localization	43/2311	201/18723	2.00e-04	2.29e-03	43
GO:00510284	Cervix	CC	mRNA transport	31/2311	130/18723	2.05e-04	2.33e-03	31
GO:00105067	Cervix	CC	regulation of autophagy	61/2311	317/18723	2.61e-04	2.87e-03	61
GO:00467008	Cervix	CC	heterocycle catabolic process	80/2311	445/18723	3.23e-04	3.42e-03	80
GO:00346559	Cervix	CC	nucleobase-containing compound catabolic process	74/2311	407/18723	3.77e-04	3.88e-03	74

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa03015	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030151	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-02	35
hsa030152	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030153	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030159	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301514	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301541	Oral cavity	EOLP	mRNA surveillance pathway	30/1218	97/8465	2.26e-05	1.20e-04	7.07e-05	30
hsa0301551	Oral cavity	EOLP	mRNA surveillance pathway	30/1218	97/8465	2.26e-05	1.20e-04	7.07e-05	30
hsa030156	Oral cavity	NEOLP	mRNA surveillance pathway	25/1112	97/8465	5.70e-04	3.18e-03	2.00e-03	25
hsa030157	Oral cavity	NEOLP	mRNA surveillance pathway	25/1112	97/8465	5.70e-04	3.18e-03	2.00e-03	25
hsa030155	Prostate	BPH	mRNA surveillance pathway	32/1718	97/8465	2.20e-03	8.63e-03	5.34e-03	32
hsa0301512	Prostate	BPH	mRNA surveillance pathway	32/1718	97/8465	2.20e-03	8.63e-03	5.34e-03	32

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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

SMG1

SNV

Missense_Mutation

rs765439624

c.9530N>A

p.Arg3177Gln

p.R3177Q

Q96Q15

protein_coding

deleterious(0.04)

probably_damaging(0.968)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

SMG1

SNV

Missense_Mutation

c.4179N>T

p.Trp1393Cys

p.W1393C

Q96Q15

protein_coding

tolerated(0.13)

possibly_damaging(0.57)

TCGA-A2-A0T0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

SMG1

SNV

Missense_Mutation

novel

c.1085G>T

p.Gly362Val

p.G362V

Q96Q15

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

SMG1

SNV

Missense_Mutation

c.8098N>C

p.Cys2700Arg

p.C2700R

Q96Q15

protein_coding

deleterious(0.03)

probably_damaging(0.986)

TCGA-A8-A08R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

SMG1

SNV

Missense_Mutation

c.10651N>G

p.Gln3551Glu

p.Q3551E

Q96Q15

protein_coding

tolerated(0.63)

benign(0.351)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMG1

SNV

Missense_Mutation

c.8524N>A

p.Glu2842Lys

p.E2842K

Q96Q15

protein_coding

tolerated(0.52)

benign(0.017)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMG1

SNV

Missense_Mutation

novel

c.6106N>T

p.His2036Tyr

p.H2036Y

Q96Q15

protein_coding

deleterious(0)

probably_damaging(0.954)

TCGA-AC-A6IW-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMG1

SNV

Missense_Mutation

novel

c.7979G>A

p.Arg2660Gln

p.R2660Q

Q96Q15

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMG1

SNV

Missense_Mutation

novel

c.4614G>T

p.Glu1538Asp

p.E1538D

Q96Q15

protein_coding

tolerated(0.99)

benign(0)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SMG1

SNV

Missense_Mutation

novel

c.5767N>A

p.Gln1923Lys

p.Q1923K

Q96Q15

protein_coding

tolerated(0.1)

possibly_damaging(0.9)

TCGA-BH-A0BG-01

Breast

breast invasive 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
23049	SMG1	DRUGGABLE GENOME, ENZYME, KINASE, SERINE THREONINE KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, DNA REPAIR		ApoC-III
23049	SMG1	DRUGGABLE GENOME, ENZYME, KINASE, SERINE THREONINE KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, DNA REPAIR	inhibitor	252827484
23049	SMG1	DRUGGABLE GENOME, ENZYME, KINASE, SERINE THREONINE KINASE, PHOSPHATIDYLINOSITOL 3 KINASE, DNA REPAIR		Bisquaternary salt

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