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: EIF5

Gene summary for EIF5

Gene summary.

Gene information	Species	Human
	Gene symbol	EIF5
	Gene ID	1983
	Gene name	eukaryotic translation initiation factor 5
	Gene Alias	EIF-5
	Cytomap	14q32.32
	Gene Type	protein-coding
	GO ID	GO:0001731
	UniProtAcc	A0A024R6Q1

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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
1983	EIF5	GSM4909277	Human	Breast	Precancer	1.37e-05	5.06e-01	0.0177
1983	EIF5	GSM4909285	Human	Breast	IDC	3.38e-03	-2.66e-01	0.21
1983	EIF5	GSM4909286	Human	Breast	IDC	1.62e-05	-2.41e-01	0.1081
1983	EIF5	GSM4909287	Human	Breast	IDC	1.16e-03	-4.08e-01	0.2057
1983	EIF5	GSM4909293	Human	Breast	IDC	1.17e-03	-3.32e-01	0.1581
1983	EIF5	GSM4909294	Human	Breast	IDC	1.79e-04	-3.68e-01	0.2022
1983	EIF5	GSM4909296	Human	Breast	IDC	7.00e-10	-3.77e-01	0.1524
1983	EIF5	GSM4909297	Human	Breast	IDC	1.79e-15	-3.42e-01	0.1517
1983	EIF5	GSM4909301	Human	Breast	IDC	1.59e-03	-3.70e-01	0.1577
1983	EIF5	GSM4909302	Human	Breast	IDC	4.19e-11	-5.55e-01	0.1545
1983	EIF5	GSM4909311	Human	Breast	IDC	6.26e-37	-6.88e-01	0.1534
1983	EIF5	GSM4909312	Human	Breast	IDC	5.68e-15	-4.79e-01	0.1552
1983	EIF5	GSM4909313	Human	Breast	IDC	1.26e-06	-4.69e-01	0.0391
1983	EIF5	GSM4909319	Human	Breast	IDC	6.07e-43	-6.40e-01	0.1563
1983	EIF5	GSM4909320	Human	Breast	IDC	3.52e-04	-3.47e-01	0.1575
1983	EIF5	GSM4909321	Human	Breast	IDC	2.92e-11	-2.65e-01	0.1559
1983	EIF5	brca1	Human	Breast	Precancer	1.15e-14	4.19e-01	-0.0338
1983	EIF5	brca10	Human	Breast	Precancer	6.85e-05	-4.55e-01	-0.0029
1983	EIF5	NCCBC14	Human	Breast	DCIS	2.66e-07	-1.32e-01	0.2021
1983	EIF5	NCCBC5	Human	Breast	DCIS	1.01e-11	-3.84e-01	0.2046

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:000173216	Prostate	BPH	formation of cytoplasmic translation initiation complex	14/3107	16/18723	1.01e-09	4.58e-08	14
GO:002241117	Prostate	BPH	cellular component disassembly	121/3107	443/18723	6.34e-09	2.25e-07	121
GO:007233217	Prostate	BPH	intrinsic apoptotic signaling pathway by p53 class mediator	34/3107	76/18723	8.04e-09	2.77e-07	34
GO:190179618	Prostate	BPH	regulation of signal transduction by p53 class mediator	38/3107	93/18723	2.31e-08	6.99e-07	38
GO:000640316	Prostate	BPH	RNA localization	65/3107	201/18723	2.76e-08	8.13e-07	65
GO:190179818	Prostate	BPH	positive regulation of signal transduction by p53 class mediator	16/3107	25/18723	1.43e-07	3.36e-06	16
GO:000961510	Prostate	BPH	response to virus	99/3107	367/18723	2.82e-07	6.07e-06	99
GO:20012448	Prostate	BPH	positive regulation of intrinsic apoptotic signaling pathway	25/3107	58/18723	1.76e-06	2.94e-05	25
GO:00329849	Prostate	BPH	protein-containing complex disassembly	65/3107	224/18723	2.19e-06	3.60e-05	65
GO:00430879	Prostate	BPH	regulation of GTPase activity	88/3107	348/18723	2.04e-05	2.49e-04	88
GO:003461216	Prostate	BPH	response to tumor necrosis factor	68/3107	253/18723	2.22e-05	2.67e-04	68
GO:005123610	Prostate	BPH	establishment of RNA localization	49/3107	166/18723	2.26e-05	2.71e-04	49
GO:005065710	Prostate	BPH	nucleic acid transport	48/3107	163/18723	2.92e-05	3.34e-04	48
GO:005065810	Prostate	BPH	RNA transport	48/3107	163/18723	2.92e-05	3.34e-04	48
GO:190225310	Prostate	BPH	regulation of intrinsic apoptotic signaling pathway by p53 class mediator	14/3107	29/18723	7.48e-05	7.24e-04	14
GO:007135616	Prostate	BPH	cellular response to tumor necrosis factor	60/3107	229/18723	1.42e-04	1.26e-03	60
GO:000641410	Prostate	BPH	translational elongation	20/3107	55/18723	3.18e-04	2.43e-03	20
GO:00017317	Prostate	BPH	formation of translation preinitiation complex	7/3107	11/18723	6.10e-04	4.16e-03	7
GO:001593110	Prostate	BPH	nucleobase-containing compound transport	55/3107	222/18723	1.12e-03	6.97e-03	55
GO:00435478	Prostate	BPH	positive regulation of GTPase activity	61/3107	255/18723	1.58e-03	9.23e-03	61

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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

EIF5

SNV

Missense_Mutation

c.39C>G

p.Phe13Leu

p.F13L

P55010

protein_coding

deleterious(0.03)

possibly_damaging(0.558)

TCGA-A2-A0YL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

EIF5

SNV

Missense_Mutation

c.238C>T

p.His80Tyr

p.H80Y

P55010

protein_coding

deleterious(0)

benign(0.277)

TCGA-A2-A0YL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

EIF5

SNV

Missense_Mutation

rs779336285

c.124G>A

p.Val42Ile

p.V42I

P55010

protein_coding

tolerated(0.55)

benign(0.013)

TCGA-D8-A1JD-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EIF5

SNV

Missense_Mutation

c.33N>G

p.Asp11Glu

p.D11E

P55010

protein_coding

deleterious(0)

possibly_damaging(0.87)

TCGA-E2-A14O-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

EIF5

insertion

In_Frame_Ins

novel

c.321_322insTGTCTTGCAGCTTATTCGCCTCAT

p.Thr107_Asp108insCysLeuAlaAlaTyrSerProHis

p.T107_D108insCLAAYSPH

P55010

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

EIF5

insertion

Nonsense_Mutation

novel

c.507_508insCGAGGTCAGGAGTTCTAGACCAGCCTAGCCAACAT

p.Asn170ArgfsTer6

p.N170Rfs*6

P55010

protein_coding

TCGA-A8-A09W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

EIF5

insertion

Nonsense_Mutation

novel

c.311_312insCGTCTGATTGCCAAGGTAATAAACTGCTCTTCAATTTAGT

p.Pro105ValfsTer2

p.P105Vfs*2

P55010

protein_coding

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

EIF5

SNV

Missense_Mutation

novel

c.1204N>A

p.Glu402Lys

p.E402K

P55010

protein_coding

deleterious(0.02)

benign(0.173)

TCGA-C5-A1MN-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

EIF5

SNV

Missense_Mutation

novel

c.89N>G

p.Asn30Ser

p.N30S

P55010

protein_coding

deleterious(0)

probably_damaging(0.946)

TCGA-MA-AA3Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

EIF5

SNV

Missense_Mutation

novel

c.173N>T

p.Gly58Val

p.G58V

P55010

protein_coding

deleterious(0)

benign(0.267)

TCGA-VS-A9V5-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

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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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