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: ATF7IP

Gene summary for ATF7IP

Gene summary.

Gene information	Species	Human
	Gene symbol	ATF7IP
	Gene ID	55729
	Gene name	activating transcription factor 7 interacting protein
	Gene Alias	AM
	Cytomap	12p13.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q6VMQ6

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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
55729	ATF7IP	CA_HPV_1	Human	Cervix	CC	2.60e-02	-6.49e-02	0.0264
55729	ATF7IP	CCI_2	Human	Cervix	CC	1.50e-07	1.15e+00	0.5249
55729	ATF7IP	CCI_3	Human	Cervix	CC	1.32e-11	1.18e+00	0.516
55729	ATF7IP	LZE4T	Human	Esophagus	ESCC	1.52e-26	6.99e-01	0.0811
55729	ATF7IP	LZE5T	Human	Esophagus	ESCC	1.38e-10	7.95e-01	0.0514
55729	ATF7IP	LZE7T	Human	Esophagus	ESCC	2.48e-17	7.12e-01	0.0667
55729	ATF7IP	LZE8T	Human	Esophagus	ESCC	2.76e-18	6.23e-01	0.067
55729	ATF7IP	LZE20T	Human	Esophagus	ESCC	1.73e-09	3.84e-01	0.0662
55729	ATF7IP	LZE22T	Human	Esophagus	ESCC	1.06e-02	1.82e-01	0.068
55729	ATF7IP	LZE24T	Human	Esophagus	ESCC	1.38e-15	5.46e-01	0.0596
55729	ATF7IP	LZE21T	Human	Esophagus	ESCC	2.46e-07	3.91e-01	0.0655
55729	ATF7IP	LZE6T	Human	Esophagus	ESCC	2.49e-08	2.84e-01	0.0845
55729	ATF7IP	P1T-E	Human	Esophagus	ESCC	3.95e-11	7.15e-01	0.0875
55729	ATF7IP	P2T-E	Human	Esophagus	ESCC	2.63e-70	1.34e+00	0.1177
55729	ATF7IP	P4T-E	Human	Esophagus	ESCC	3.12e-16	3.83e-01	0.1323
55729	ATF7IP	P5T-E	Human	Esophagus	ESCC	2.00e-12	2.83e-01	0.1327
55729	ATF7IP	P8T-E	Human	Esophagus	ESCC	2.23e-38	6.94e-01	0.0889
55729	ATF7IP	P9T-E	Human	Esophagus	ESCC	6.54e-07	1.61e-01	0.1131
55729	ATF7IP	P10T-E	Human	Esophagus	ESCC	2.07e-22	4.05e-01	0.116
55729	ATF7IP	P11T-E	Human	Esophagus	ESCC	1.83e-19	6.69e-01	0.1426

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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
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
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:2001252110	Skin	cSCC	positive regulation of chromosome organization	45/4864	82/18723	2.47e-08	6.89e-07	45
GO:000632519	Skin	cSCC	chromatin organization	147/4864	409/18723	4.41e-06	6.52e-05	147
GO:000635212	Skin	cSCC	DNA-templated transcription, initiation	57/4864	130/18723	7.28e-06	1.01e-04	57
GO:00063674	Skin	cSCC	transcription initiation from RNA polymerase II promoter	37/4864	77/18723	2.53e-05	2.87e-04	37
GO:00708974	Skin	cSCC	transcription preinitiation complex assembly	21/4864	36/18723	3.98e-05	4.26e-04	21
GO:00718241	Skin	cSCC	protein-DNA complex subunit organization	87/4864	241/18723	3.09e-04	2.47e-03	87
GO:00511233	Skin	cSCC	RNA polymerase II preinitiation complex assembly	14/4864	24/18723	7.90e-04	5.47e-03	14
GO:004341411	Skin	cSCC	macromolecule methylation	107/4864	316/18723	1.03e-03	6.94e-03	107
GO:00322593	Skin	cSCC	methylation	120/4864	364/18723	1.61e-03	9.93e-03	120
GO:006096814	Skin	cSCC	regulation of gene silencing	33/4864	81/18723	2.59e-03	1.47e-02	33
GO:20001425	Skin	cSCC	regulation of DNA-templated transcription, initiation	18/4864	40/18723	7.10e-03	3.40e-02	18
GO:004002912	Skin	cSCC	regulation of gene expression, epigenetic	39/4864	105/18723	7.56e-03	3.53e-02	39
GO:0031647113	Thyroid	PTC	regulation of protein stability	174/5968	298/18723	2.05e-21	4.05e-19	174
GO:0050821113	Thyroid	PTC	protein stabilization	115/5968	191/18723	5.67e-16	4.31e-14	115
GO:0043254113	Thyroid	PTC	regulation of protein-containing complex assembly	215/5968	428/18723	1.23e-15	9.09e-14	215
GO:003304419	Thyroid	PTC	regulation of chromosome organization	102/5968	187/18723	1.04e-10	3.58e-09	102
GO:000632520	Thyroid	PTC	chromatin organization	183/5968	409/18723	2.55e-08	5.70e-07	183
GO:2001252111	Thyroid	PTC	positive regulation of chromosome organization	48/5968	82/18723	5.65e-07	9.04e-06	48
GO:00400297	Thyroid	PTC	regulation of gene expression, epigenetic	57/5968	105/18723	1.60e-06	2.25e-05	57
GO:00063675	Thyroid	PTC	transcription initiation from RNA polymerase II promoter	44/5968	77/18723	4.04e-06	5.05e-05	44

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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

ATF7IP

SNV

Missense_Mutation

rs770349087

c.3026G>A

p.Arg1009Gln

p.R1009Q

Q6VMQ6

protein_coding

deleterious_low_confidence(0.02)

benign(0.267)

TCGA-A8-A08O-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

ATF7IP

SNV

Missense_Mutation

c.2681G>T

p.Arg894Met

p.R894M

Q6VMQ6

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATF7IP

SNV

Missense_Mutation

c.3730N>A

p.Gly1244Ser

p.G1244S

Q6VMQ6

protein_coding

tolerated_low_confidence(0.09)

probably_damaging(0.999)

TCGA-BH-A18S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ATF7IP

SNV

Missense_Mutation

c.2791N>A

p.Glu931Lys

p.E931K

Q6VMQ6

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.783)

TCGA-D8-A1J9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ATF7IP

insertion

Frame_Shift_Ins

novel

c.2342_2343insACAAAAATTATCCAGGCATGATGGCTGGT

p.Pro782GlnfsTer20

p.P782Qfs*20

Q6VMQ6

protein_coding

TCGA-BH-A0HK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

ATF7IP

deletion

Frame_Shift_Del

c.2834_2835delNN

p.Asn945LysfsTer9

p.N945Kfs*9

Q6VMQ6

protein_coding

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

ATF7IP

SNV

Missense_Mutation

rs774984681

c.55N>A

p.Val19Ile

p.V19I

Q6VMQ6

protein_coding

tolerated_low_confidence(0.08)

benign(0.015)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ATF7IP

SNV

Missense_Mutation

novel

c.1140N>T

p.Glu380Asp

p.E380D

Q6VMQ6

protein_coding

tolerated_low_confidence(0.11)

benign(0.003)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

ATF7IP

SNV

Missense_Mutation

c.1273N>C

p.Asp425His

p.D425H

Q6VMQ6

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.661)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

ATF7IP

SNV

Missense_Mutation

novel

c.2218G>C

p.Val740Leu

p.V740L

Q6VMQ6

protein_coding

deleterious_low_confidence(0.05)

benign(0.007)

TCGA-C5-A7CK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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