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: HN1

Gene summary for HN1

Gene summary.

Gene information	Species	Human
	Gene symbol	HN1
	Gene ID	51155
	Gene name	Jupiter microtubule associated homolog 1
	Gene Alias	ARM2
	Cytomap	17q25.1
	Gene Type	protein-coding
	GO ID	GO:0005575
	UniProtAcc	Q9UK76

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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
51155	HN1	GSM4909281	Human	Breast	IDC	3.69e-10	-2.03e-01	0.21
51155	HN1	GSM4909282	Human	Breast	IDC	7.71e-11	-2.03e-01	-0.0288
51155	HN1	GSM4909285	Human	Breast	IDC	7.71e-11	-2.03e-01	0.21
51155	HN1	GSM4909286	Human	Breast	IDC	1.69e-10	-2.03e-01	0.1081
51155	HN1	GSM4909287	Human	Breast	IDC	5.04e-09	-2.03e-01	0.2057
51155	HN1	GSM4909290	Human	Breast	IDC	6.20e-06	-2.03e-01	0.2096
51155	HN1	GSM4909291	Human	Breast	IDC	1.86e-04	-2.03e-01	0.1753
51155	HN1	GSM4909293	Human	Breast	IDC	7.71e-11	-2.03e-01	0.1581
51155	HN1	GSM4909294	Human	Breast	IDC	3.52e-11	-2.03e-01	0.2022
51155	HN1	GSM4909295	Human	Breast	IDC	4.17e-03	-2.03e-01	0.0898
51155	HN1	GSM4909296	Human	Breast	IDC	1.69e-10	-2.03e-01	0.1524
51155	HN1	GSM4909297	Human	Breast	IDC	3.69e-10	-2.03e-01	0.1517
51155	HN1	GSM4909298	Human	Breast	IDC	1.69e-10	-2.03e-01	0.1551
51155	HN1	GSM4909299	Human	Breast	IDC	3.69e-10	-2.03e-01	0.035
51155	HN1	GSM4909300	Human	Breast	IDC	1.59e-02	-2.03e-01	0.0334
51155	HN1	GSM4909301	Human	Breast	IDC	3.30e-12	-2.03e-01	0.1577
51155	HN1	GSM4909302	Human	Breast	IDC	7.22e-09	-2.03e-01	0.1545
51155	HN1	GSM4909304	Human	Breast	IDC	1.60e-11	-2.03e-01	0.1636
51155	HN1	GSM4909305	Human	Breast	IDC	1.14e-05	-2.03e-01	0.0436
51155	HN1	GSM4909306	Human	Breast	IDC	7.71e-11	-2.03e-01	0.1564

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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
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
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

∗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:009950411	Lung	AIS	synaptic vesicle cycle	36/1849	181/18723	3.42e-05	1.05e-03	36
GO:003010012	Lung	AIS	regulation of endocytosis	40/1849	211/18723	4.10e-05	1.23e-03	40
GO:004848811	Lung	AIS	synaptic vesicle endocytosis	17/1849	62/18723	7.32e-05	1.91e-03	17
GO:014023811	Lung	AIS	presynaptic endocytosis	17/1849	62/18723	7.32e-05	1.91e-03	17
GO:004217713	Lung	AIS	negative regulation of protein catabolic process	26/1849	121/18723	1.09e-04	2.57e-03	26
GO:009016212	Lung	AIS	establishment of epithelial cell polarity	11/1849	31/18723	1.10e-04	2.57e-03	11
GO:000726612	Lung	AIS	Rho protein signal transduction	28/1849	137/18723	1.51e-04	3.22e-03	28
GO:004825912	Lung	AIS	regulation of receptor-mediated endocytosis	24/1849	110/18723	1.54e-04	3.26e-03	24
GO:004311212	Lung	AIS	receptor metabolic process	32/1849	166/18723	1.68e-04	3.53e-03	32
GO:00069291	Lung	AIS	substrate-dependent cell migration	9/1849	23/18723	1.98e-04	4.07e-03	9
GO:003150311	Lung	AIS	protein-containing complex localization	39/1849	220/18723	2.24e-04	4.51e-03	39
GO:000740911	Lung	AIS	axonogenesis	64/1849	418/18723	2.62e-04	5.04e-03	64
GO:003646511	Lung	AIS	synaptic vesicle recycling	18/1849	75/18723	2.89e-04	5.40e-03	18
GO:190336312	Lung	AIS	negative regulation of cellular protein catabolic process	18/1849	75/18723	2.89e-04	5.40e-03	18
GO:004586113	Lung	AIS	negative regulation of proteolysis	55/1849	351/18723	3.87e-04	6.72e-03	55
GO:006156411	Lung	AIS	axon development	69/1849	467/18723	4.37e-04	7.41e-03	69
GO:009917311	Lung	AIS	postsynapse organization	31/1849	168/18723	4.67e-04	7.79e-03	31
GO:004395411	Lung	AIS	cellular component maintenance	15/1849	61/18723	6.88e-04	1.02e-02	15
GO:003508811	Lung	AIS	establishment or maintenance of apical/basal cell polarity	13/1849	49/18723	7.13e-04	1.04e-02	13
GO:006124511	Lung	AIS	establishment or maintenance of bipolar cell polarity	13/1849	49/18723	7.13e-04	1.04e-02	13

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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

HN1

SNV

Missense_Mutation

rs765086350

c.194N>T

p.Ser65Leu

p.S65L

Q9UK76

protein_coding

deleterious(0.01)

benign(0.08)

TCGA-LP-A7HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HN1

SNV

Missense_Mutation

novel

c.70N>A

p.Pro24Thr

p.P24T

Q9UK76

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-LP-A7HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HN1

SNV

Missense_Mutation

c.464N>A

p.Arg155His

p.R155H

Q9UK76

protein_coding

tolerated_low_confidence(0.08)

benign(0.258)

TCGA-AA-A01D-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

capecitabine

HN1

SNV

Missense_Mutation

c.122N>A

p.Pro41His

p.P41H

Q9UK76

protein_coding

deleterious(0)

probably_damaging(0.925)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HN1

SNV

Missense_Mutation

rs758089157

c.361C>T

p.Arg121Cys

p.R121C

Q9UK76

protein_coding

deleterious_low_confidence(0.01)

benign(0.319)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

HN1

SNV

Missense_Mutation

c.275C>T

p.Ser92Phe

p.S92F

Q9UK76

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.471)

TCGA-D1-A103-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HN1

SNV

Missense_Mutation

rs371693377

c.419C>T

p.Ala140Val

p.A140V

Q9UK76

protein_coding

tolerated_low_confidence(0.32)

benign(0.003)

TCGA-D1-A175-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

HN1

SNV

Missense_Mutation

novel

c.73N>T

p.Gly25Cys

p.G25C

Q9UK76

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-DF-A2KN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

HN1

insertion

Frame_Shift_Ins

novel

c.415_416insC

p.Leu139ProfsTer11

p.L139Pfs*11

Q9UK76

protein_coding

TCGA-EO-A3AU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HN1

SNV

Missense_Mutation

rs868058942

c.64N>T

p.Arg22Trp

p.R22W

Q9UK76

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.958)

TCGA-BR-4370-01

Stomach

stomach adenocarcinoma

Female

>=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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