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:004325410	Cervix	CC	regulation of protein-containing complex assembly	96/2311	428/18723	2.91e-09	3.05e-07	96
GO:003164710	Cervix	CC	regulation of protein stability	63/2311	298/18723	1.14e-05	2.45e-04	63
GO:00063257	Cervix	CC	chromatin organization	78/2311	409/18723	5.40e-05	8.02e-04	78
GO:005082110	Cervix	CC	protein stabilization	43/2311	191/18723	5.90e-05	8.54e-04	43
GO:0031647111	Esophagus	ESCC	regulation of protein stability	223/8552	298/18723	5.76e-25	1.52e-22	223
GO:003304416	Esophagus	ESCC	regulation of chromosome organization	145/8552	187/18723	3.80e-19	4.31e-17	145
GO:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:0050821111	Esophagus	ESCC	protein stabilization	140/8552	191/18723	6.50e-15	3.61e-13	140
GO:00434143	Esophagus	ESCC	macromolecule methylation	199/8552	316/18723	3.44e-10	9.57e-09	199
GO:200125219	Esophagus	ESCC	positive regulation of chromosome organization	64/8552	82/18723	1.98e-09	4.52e-08	64
GO:00322592	Esophagus	ESCC	methylation	222/8552	364/18723	2.26e-09	5.09e-08	222
GO:000632517	Esophagus	ESCC	chromatin organization	240/8552	409/18723	6.52e-08	1.14e-06	240
GO:00400295	Esophagus	ESCC	regulation of gene expression, epigenetic	74/8552	105/18723	2.24e-07	3.42e-06	74
GO:00063673	Esophagus	ESCC	transcription initiation from RNA polymerase II promoter	56/8552	77/18723	1.30e-06	1.59e-05	56
GO:000635211	Esophagus	ESCC	DNA-templated transcription, initiation	86/8552	130/18723	1.88e-06	2.19e-05	86
GO:00708973	Esophagus	ESCC	transcription preinitiation complex assembly	30/8552	36/18723	3.60e-06	3.95e-05	30
GO:00602603	Esophagus	ESCC	regulation of transcription initiation from RNA polymerase II promoter	25/8552	33/18723	4.30e-04	2.43e-03	25
GO:200014212	Esophagus	ESCC	regulation of DNA-templated transcription, initiation	29/8552	40/18723	5.32e-04	2.93e-03	29
GO:00708281	Esophagus	ESCC	heterochromatin organization	31/8552	46/18723	2.42e-03	1.06e-02	31
GO:00511232	Esophagus	ESCC	RNA polymerase II preinitiation complex assembly	18/8552	24/18723	3.43e-03	1.41e-02	18

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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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