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: ALKBH7

Gene summary for ALKBH7

Gene summary.

Gene information	Species	Human
	Gene symbol	ALKBH7
	Gene ID	84266
	Gene name	alkB homolog 7
	Gene Alias	ABH7
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	Q9BT30

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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
84266	ALKBH7	CA_HPV_1	Human	Cervix	CC	1.31e-07	-3.82e-01	0.0264
84266	ALKBH7	CA_HPV_2	Human	Cervix	CC	9.02e-04	-3.08e-01	0.0391
84266	ALKBH7	CA_HPV_3	Human	Cervix	CC	2.73e-02	8.79e-02	0.0414
84266	ALKBH7	N_HPV_2	Human	Cervix	N_HPV	1.20e-02	-3.27e-02	-0.0131
84266	ALKBH7	CCI_1	Human	Cervix	CC	3.04e-11	-6.67e-01	0.528
84266	ALKBH7	CCI_2	Human	Cervix	CC	8.67e-08	-6.45e-01	0.5249
84266	ALKBH7	CCI_3	Human	Cervix	CC	6.03e-15	-6.67e-01	0.516
84266	ALKBH7	CCII_1	Human	Cervix	CC	1.35e-20	-6.67e-01	0.3249
84266	ALKBH7	Tumor	Human	Cervix	CC	1.30e-03	-3.48e-01	0.1241
84266	ALKBH7	sample3	Human	Cervix	CC	9.98e-06	-3.65e-01	0.1387
84266	ALKBH7	H2	Human	Cervix	HSIL_HPV	8.16e-04	-3.40e-01	0.0632
84266	ALKBH7	L1	Human	Cervix	CC	3.83e-07	-4.01e-01	0.0802
84266	ALKBH7	T3	Human	Cervix	CC	9.85e-11	-3.78e-01	0.1389
84266	ALKBH7	HTA11_3410_2000001011	Human	Colorectum	AD	5.28e-15	4.07e-01	0.0155
84266	ALKBH7	HTA11_2487_2000001011	Human	Colorectum	SER	2.29e-35	9.10e-01	-0.1808
84266	ALKBH7	HTA11_2951_2000001011	Human	Colorectum	AD	1.86e-06	4.65e-01	0.0216
84266	ALKBH7	HTA11_1938_2000001011	Human	Colorectum	AD	8.37e-22	6.58e-01	-0.0811
84266	ALKBH7	HTA11_78_2000001011	Human	Colorectum	AD	6.55e-05	2.62e-01	-0.1088
84266	ALKBH7	HTA11_347_2000001011	Human	Colorectum	AD	1.30e-49	8.74e-01	-0.1954
84266	ALKBH7	HTA11_411_2000001011	Human	Colorectum	SER	3.66e-14	1.24e+00	-0.2602

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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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:000683919	Oral cavity	LP	mitochondrial transport	119/4623	254/18723	1.06e-14	1.33e-12	119
GO:000700617	Oral cavity	LP	mitochondrial membrane organization	61/4623	116/18723	9.44e-11	5.63e-09	61
GO:004690216	Oral cavity	LP	regulation of mitochondrial membrane permeability	31/4623	63/18723	2.20e-05	3.58e-04	31
GO:009055916	Oral cavity	LP	regulation of membrane permeability	35/4623	78/18723	7.85e-05	1.02e-03	35
GO:005123519	Oral cavity	LP	maintenance of location	111/4623	327/18723	9.62e-05	1.20e-03	111
GO:000683916	Prostate	BPH	mitochondrial transport	79/3107	254/18723	6.77e-09	2.38e-07	79
GO:005123516	Prostate	BPH	maintenance of location	80/3107	327/18723	1.55e-04	1.36e-03	80
GO:00070069	Prostate	BPH	mitochondrial membrane organization	35/3107	116/18723	1.98e-04	1.63e-03	35
GO:00905597	Prostate	BPH	regulation of membrane permeability	25/3107	78/18723	5.74e-04	3.99e-03	25
GO:00469027	Prostate	BPH	regulation of mitochondrial membrane permeability	19/3107	63/18723	5.36e-03	2.49e-02	19
GO:000683917	Prostate	Tumor	mitochondrial transport	84/3246	254/18723	7.17e-10	3.57e-08	84
GO:000700616	Prostate	Tumor	mitochondrial membrane organization	35/3246	116/18723	4.65e-04	3.48e-03	35
GO:009055915	Prostate	Tumor	regulation of membrane permeability	25/3246	78/18723	1.11e-03	7.12e-03	25
GO:005123517	Prostate	Tumor	maintenance of location	78/3246	327/18723	1.56e-03	9.55e-03	78
GO:004690215	Prostate	Tumor	regulation of mitochondrial membrane permeability	19/3246	63/18723	8.63e-03	3.75e-02	19
GO:000683927	Skin	cSCC	mitochondrial transport	124/4864	254/18723	3.54e-15	2.81e-13	124
GO:0007006110	Skin	cSCC	mitochondrial membrane organization	64/4864	116/18723	2.16e-11	1.08e-09	64
GO:004690218	Skin	cSCC	regulation of mitochondrial membrane permeability	30/4864	63/18723	1.76e-04	1.50e-03	30
GO:009055917	Skin	cSCC	regulation of membrane permeability	35/4864	78/18723	2.32e-04	1.91e-03	35
GO:005123527	Skin	cSCC	maintenance of location	106/4864	327/18723	5.17e-03	2.61e-02	106

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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

ALKBH7

SNV

Missense_Mutation

novel

c.218N>C

p.Phe73Ser

p.F73S

Q9BT30

protein_coding

deleterious(0)

probably_damaging(0.912)

TCGA-A8-A09T-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ALKBH7

SNV

Missense_Mutation

c.429G>A

p.Met143Ile

p.M143I

Q9BT30

protein_coding

deleterious(0)

probably_damaging(0.97)

TCGA-AR-A0U3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ALKBH7

SNV

Missense_Mutation

novel

c.367N>T

p.Asp123Tyr

p.D123Y

Q9BT30

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

ALKBH7

SNV

Missense_Mutation

rs756913702

c.607N>T

p.Arg203Cys

p.R203C

Q9BT30

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

ALKBH7

insertion

Nonsense_Mutation

novel

c.365_366insTCTTCTGCACTGTAACTGCTAGCAGC

p.Asp123LeufsTer7

p.D123Lfs*7

Q9BT30

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

ALKBH7

SNV

Missense_Mutation

rs755922067

c.590N>A

p.Arg197His

p.R197H

Q9BT30

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ALKBH7

SNV

Missense_Mutation

rs147538989

c.586N>T

p.Arg196Trp

p.R196W

Q9BT30

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B5-A5OC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

cisplatin

ALKBH7

SNV

Missense_Mutation

novel

c.364N>A

p.Val122Met

p.V122M

Q9BT30

protein_coding

deleterious(0)

probably_damaging(0.979)

TCGA-E6-A2P8-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

ALKBH7

SNV

Missense_Mutation

rs199888358

c.271N>T

p.Arg91Cys

p.R91C

Q9BT30

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-EY-A1H0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

taxol

ALKBH7

SNV

Missense_Mutation

c.496N>C

p.Ile166Leu

p.I166L

Q9BT30

protein_coding

deleterious(0.01)

probably_damaging(0.947)

TCGA-BC-A69H-01

Liver

liver hepatocellular carcinoma

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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