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: HP1BP3

Gene summary for HP1BP3

Gene summary.

Gene information	Species	Human
	Gene symbol	HP1BP3
	Gene ID	50809
	Gene name	heterochromatin protein 1 binding protein 3
	Gene Alias	HP1-BP74
	Cytomap	1p36.12
	Gene Type	protein-coding
	GO ID	GO:0001666
	UniProtAcc	Q5SSJ5

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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
50809	HP1BP3	GSM4909285	Human	Breast	IDC	4.41e-04	-2.62e-01	0.21
50809	HP1BP3	GSM4909294	Human	Breast	IDC	2.85e-02	-8.09e-02	0.2022
50809	HP1BP3	GSM4909296	Human	Breast	IDC	4.07e-12	-1.91e-01	0.1524
50809	HP1BP3	GSM4909297	Human	Breast	IDC	6.91e-15	-1.23e-01	0.1517
50809	HP1BP3	GSM4909301	Human	Breast	IDC	1.68e-02	1.84e-01	0.1577
50809	HP1BP3	GSM4909311	Human	Breast	IDC	3.98e-27	-3.81e-01	0.1534
50809	HP1BP3	GSM4909312	Human	Breast	IDC	1.26e-13	-3.43e-01	0.1552
50809	HP1BP3	GSM4909316	Human	Breast	IDC	2.65e-03	-2.54e-01	0.21
50809	HP1BP3	GSM4909319	Human	Breast	IDC	6.68e-31	-2.39e-01	0.1563
50809	HP1BP3	GSM4909320	Human	Breast	IDC	5.93e-05	-3.32e-01	0.1575
50809	HP1BP3	GSM4909321	Human	Breast	IDC	2.09e-12	-1.88e-01	0.1559
50809	HP1BP3	brca10	Human	Breast	Precancer	1.12e-02	-2.59e-01	-0.0029
50809	HP1BP3	M2	Human	Breast	IDC	5.73e-03	4.83e-02	0.21
50809	HP1BP3	NCCBC14	Human	Breast	DCIS	1.24e-08	-4.39e-02	0.2021
50809	HP1BP3	NCCBC3	Human	Breast	DCIS	2.86e-02	9.73e-02	0.1198
50809	HP1BP3	NCCBC5	Human	Breast	DCIS	1.05e-09	-1.93e-01	0.2046
50809	HP1BP3	P1	Human	Breast	IDC	7.86e-21	-2.57e-02	0.1527
50809	HP1BP3	P2	Human	Breast	IDC	3.82e-04	2.05e-01	0.21
50809	HP1BP3	P3	Human	Breast	IDC	1.93e-02	5.51e-01	0.1542
50809	HP1BP3	DCIS2	Human	Breast	DCIS	1.31e-56	3.92e-01	0.0085

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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
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:00362939	Breast	Precancer	response to decreased oxygen levels	53/1080	322/18723	4.09e-12	6.84e-10	53
GO:00016669	Breast	Precancer	response to hypoxia	51/1080	307/18723	7.33e-12	1.11e-09	51
GO:00704829	Breast	Precancer	response to oxygen levels	55/1080	347/18723	7.47e-12	1.11e-09	55
GO:00362948	Breast	Precancer	cellular response to decreased oxygen levels	31/1080	161/18723	2.61e-09	2.11e-07	31
GO:00714538	Breast	Precancer	cellular response to oxygen levels	32/1080	177/18723	7.32e-09	5.52e-07	32
GO:00714565	Breast	Precancer	cellular response to hypoxia	29/1080	151/18723	8.98e-09	6.50e-07	29
GO:007048214	Breast	IDC	response to oxygen levels	64/1434	347/18723	3.45e-11	5.57e-09	64
GO:003629314	Breast	IDC	response to decreased oxygen levels	60/1434	322/18723	9.26e-11	1.25e-08	60
GO:000166614	Breast	IDC	response to hypoxia	58/1434	307/18723	1.09e-10	1.38e-08	58
GO:003629413	Breast	IDC	cellular response to decreased oxygen levels	34/1434	161/18723	4.73e-08	3.02e-06	34
GO:007145613	Breast	IDC	cellular response to hypoxia	32/1434	151/18723	1.07e-07	6.26e-06	32
GO:007145313	Breast	IDC	cellular response to oxygen levels	35/1434	177/18723	1.68e-07	9.10e-06	35
GO:00325358	Breast	IDC	regulation of cellular component size	45/1434	383/18723	2.72e-03	2.41e-02	45
GO:003629323	Breast	DCIS	response to decreased oxygen levels	60/1390	322/18723	2.64e-11	4.56e-09	60
GO:007048223	Breast	DCIS	response to oxygen levels	63/1390	347/18723	2.66e-11	4.56e-09	63
GO:000166623	Breast	DCIS	response to hypoxia	58/1390	307/18723	3.19e-11	5.16e-09	58
GO:003629422	Breast	DCIS	cellular response to decreased oxygen levels	34/1390	161/18723	2.21e-08	1.49e-06	34
GO:007145622	Breast	DCIS	cellular response to hypoxia	32/1390	151/18723	5.21e-08	3.17e-06	32
GO:007145322	Breast	DCIS	cellular response to oxygen levels	35/1390	177/18723	7.89e-08	4.47e-06	35
GO:003253514	Breast	DCIS	regulation of cellular component size	44/1390	383/18723	2.58e-03	2.30e-02	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

HP1BP3

SNV

Missense_Mutation

c.959A>G

p.Lys320Arg

p.K320R

Q5SSJ5

protein_coding

deleterious(0)

possibly_damaging(0.908)

TCGA-AR-A24L-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

HP1BP3

SNV

Missense_Mutation

c.653N>T

p.Gln218Leu

p.Q218L

Q5SSJ5

protein_coding

deleterious(0)

probably_damaging(0.968)

TCGA-BH-A18K-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HP1BP3

SNV

Missense_Mutation

c.1279N>C

p.Glu427Gln

p.E427Q

Q5SSJ5

protein_coding

tolerated(0.59)

benign(0.001)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HP1BP3

SNV

Missense_Mutation

novel

c.626G>A

p.Arg209Lys

p.R209K

Q5SSJ5

protein_coding

tolerated(0.5)

probably_damaging(0.963)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

HP1BP3

SNV

Missense_Mutation

novel

c.1388C>T

p.Ala463Val

p.A463V

Q5SSJ5

protein_coding

tolerated_low_confidence(0.18)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HP1BP3

SNV

Missense_Mutation

rs771916157

c.1352C>T

p.Pro451Leu

p.P451L

Q5SSJ5

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.995)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HP1BP3

SNV

Missense_Mutation

c.928N>C

p.Glu310Gln

p.E310Q

Q5SSJ5

protein_coding

deleterious(0.02)

benign(0.419)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HP1BP3

insertion

Frame_Shift_Ins

novel

c.1536_1537insATTG

p.Ser513IlefsTer9

p.S513Ifs*9

Q5SSJ5

protein_coding

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

HP1BP3

deletion

Frame_Shift_Del

c.394delA

p.Thr132GlnfsTer13

p.T132Qfs*13

Q5SSJ5

protein_coding

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

HP1BP3

SNV

Missense_Mutation

c.1511N>T

p.Thr504Met

p.T504M

Q5SSJ5

protein_coding

deleterious_low_confidence(0)

benign(0.416)

TCGA-AA-A01R-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

5-fluorouracil

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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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