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: ATL2

Gene summary for ATL2

Gene summary.

Gene information	Species	Human
	Gene symbol	ATL2
	Gene ID	64225
	Gene name	atlastin GTPase 2
	Gene Alias	ARL3IP2
	Cytomap	2p22.2-p22.1
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	Q8NHH9

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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
64225	ATL2	CCI_2	Human	Cervix	CC	4.95e-07	8.04e-01	0.5249
64225	ATL2	CCI_3	Human	Cervix	CC	6.04e-08	6.12e-01	0.516
64225	ATL2	HTA11_3410_2000001011	Human	Colorectum	AD	1.31e-29	8.93e-01	0.0155
64225	ATL2	HTA11_2487_2000001011	Human	Colorectum	SER	7.30e-04	4.39e-01	-0.1808
64225	ATL2	HTA11_2951_2000001011	Human	Colorectum	AD	4.18e-03	5.85e-01	0.0216
64225	ATL2	HTA11_1938_2000001011	Human	Colorectum	AD	1.07e-22	1.09e+00	-0.0811
64225	ATL2	HTA11_347_2000001011	Human	Colorectum	AD	5.74e-31	9.20e-01	-0.1954
64225	ATL2	HTA11_411_2000001011	Human	Colorectum	SER	1.83e-08	1.13e+00	-0.2602
64225	ATL2	HTA11_3361_2000001011	Human	Colorectum	AD	9.76e-09	7.20e-01	-0.1207
64225	ATL2	HTA11_83_2000001011	Human	Colorectum	SER	1.20e-04	6.57e-01	-0.1526
64225	ATL2	HTA11_696_2000001011	Human	Colorectum	AD	8.41e-26	1.17e+00	-0.1464
64225	ATL2	HTA11_866_2000001011	Human	Colorectum	AD	9.65e-04	3.39e-01	-0.1001
64225	ATL2	HTA11_1391_2000001011	Human	Colorectum	AD	1.59e-03	4.20e-01	-0.059
64225	ATL2	HTA11_2992_2000001011	Human	Colorectum	SER	1.42e-14	1.31e+00	-0.1706
64225	ATL2	HTA11_5212_2000001011	Human	Colorectum	AD	2.73e-11	1.04e+00	-0.2061
64225	ATL2	HTA11_5216_2000001011	Human	Colorectum	SER	7.21e-17	1.42e+00	-0.1462
64225	ATL2	HTA11_546_2000001011	Human	Colorectum	AD	9.91e-14	1.12e+00	-0.0842
64225	ATL2	HTA11_99999965104_69814	Human	Colorectum	MSS	1.20e-12	7.95e-01	0.281
64225	ATL2	A001-C-207	Human	Colorectum	FAP	6.78e-04	-2.97e-01	0.1278
64225	ATL2	A015-C-203	Human	Colorectum	FAP	1.67e-19	-2.91e-01	-0.1294

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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
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
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:00070304	Cervix	CC	Golgi organization	32/2311	157/18723	2.78e-03	1.87e-02	32
GO:0007029	Colorectum	AD	endoplasmic reticulum organization	31/3918	87/18723	1.08e-03	1.00e-02	31
GO:0071786	Colorectum	AD	endoplasmic reticulum tubular network organization	9/3918	18/18723	5.82e-03	3.67e-02	9
GO:00070291	Colorectum	SER	endoplasmic reticulum organization	23/2897	87/18723	5.77e-03	4.23e-02	23
GO:00070305	Endometrium	AEH	Golgi organization	32/2100	157/18723	5.73e-04	5.69e-03	32
GO:000703012	Endometrium	EEC	Golgi organization	32/2168	157/18723	9.87e-04	8.76e-03	32
GO:00070295	Esophagus	HGIN	endoplasmic reticulum organization	22/2587	87/18723	3.07e-03	2.90e-02	22
GO:000702914	Esophagus	ESCC	endoplasmic reticulum organization	65/8552	87/18723	3.28e-08	6.08e-07	65
GO:00070308	Esophagus	ESCC	Golgi organization	101/8552	157/18723	1.78e-06	2.10e-05	101
GO:00717865	Esophagus	ESCC	endoplasmic reticulum tubular network organization	15/8552	18/18723	1.20e-03	5.88e-03	15
GO:00512592	Esophagus	ESCC	protein complex oligomerization	130/8552	238/18723	3.29e-03	1.36e-02	130
GO:0007030	Liver	NAFLD	Golgi organization	36/1882	157/18723	1.76e-06	7.68e-05	36
GO:00717863	Liver	NAFLD	endoplasmic reticulum tubular network organization	6/1882	18/18723	6.55e-03	4.69e-02	6
GO:00070301	Liver	Cirrhotic	Golgi organization	68/4634	157/18723	2.57e-07	6.41e-06	68
GO:00070292	Liver	Cirrhotic	endoplasmic reticulum organization	42/4634	87/18723	1.67e-06	3.22e-05	42
GO:00717861	Liver	Cirrhotic	endoplasmic reticulum tubular network organization	11/4634	18/18723	1.13e-03	7.73e-03	11
GO:000702911	Liver	HCC	endoplasmic reticulum organization	64/7958	87/18723	3.92e-09	1.04e-07	64
GO:00070302	Liver	HCC	Golgi organization	99/7958	157/18723	1.54e-07	2.85e-06	99
GO:00717862	Liver	HCC	endoplasmic reticulum tubular network organization	15/7958	18/18723	4.74e-04	3.12e-03	15
GO:0090158	Liver	HCC	endoplasmic reticulum membrane organization	10/7958	13/18723	1.28e-02	4.61e-02	10

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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

ATL2

SNV

Missense_Mutation

c.1480N>G

p.Phe494Val

p.F494V

Q8NHH9

protein_coding

tolerated(0.08)

benign(0.04)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATL2

SNV

Missense_Mutation

c.932N>A

p.Gly311Glu

p.G311E

Q8NHH9

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATL2

SNV

Missense_Mutation

rs760807574

c.1659N>C

p.Leu553Phe

p.L553F

Q8NHH9

protein_coding

tolerated(0.33)

benign(0)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATL2

SNV

Missense_Mutation

c.193N>G

p.Leu65Val

p.L65V

Q8NHH9

protein_coding

tolerated(0.36)

benign(0.001)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATL2

insertion

In_Frame_Ins

novel

c.516_517insAAGGGAAAAAAAAGGAAGCTATTTACATTTCTTGAGAGC

p.Met172_Asp173insLysGlyLysLysArgLysLeuPheThrPheLeuGluSer

p.M172_D173insKGKKRKLFTFLES

Q8NHH9

protein_coding

TCGA-A8-A0A1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

ATL2

insertion

Frame_Shift_Ins

novel

c.1297_1298insGATTAGTCACTAAAAAACC

p.Lys433ArgfsTer13

p.K433Rfs*13

Q8NHH9

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATL2

insertion

Frame_Shift_Ins

novel

c.1297_1298insGATTAGTCACTAAAAAACC

p.Lys433ArgfsTer13

p.K433Rfs*13

Q8NHH9

protein_coding

TCGA-AR-A0U2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

tamoxiphen

ATL2

SNV

Missense_Mutation

c.874N>C

p.Gly292Arg

p.G292R

Q8NHH9

protein_coding

tolerated(0.14)

benign(0.014)

TCGA-EA-A1QT-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ATL2

SNV

Missense_Mutation

c.979N>A

p.Leu327Met

p.L327M

Q8NHH9

protein_coding

deleterious(0.04)

possibly_damaging(0.903)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

ATL2

SNV

Missense_Mutation

c.1288N>T

p.Arg430Cys

p.R430C

Q8NHH9

protein_coding

tolerated(0.09)

benign(0.031)

TCGA-AZ-4315-01

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

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