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: HERPUD1

Gene summary for HERPUD1

Gene summary.

Gene information	Species	Human
	Gene symbol	HERPUD1
	Gene ID	9709
	Gene name	homocysteine inducible ER protein with ubiquitin like domain 1
	Gene Alias	HERP
	Cytomap	16q13
	Gene Type	protein-coding
	GO ID	GO:0006464
	UniProtAcc	Q15011

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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
9709	HERPUD1	GSM4909286	Human	Breast	IDC	5.17e-16	-5.31e-01	0.1081
9709	HERPUD1	GSM4909294	Human	Breast	IDC	2.77e-04	-3.91e-01	0.2022
9709	HERPUD1	GSM4909296	Human	Breast	IDC	1.01e-18	-5.23e-01	0.1524
9709	HERPUD1	GSM4909297	Human	Breast	IDC	5.30e-13	-1.87e-01	0.1517
9709	HERPUD1	GSM4909301	Human	Breast	IDC	3.70e-08	-4.02e-01	0.1577
9709	HERPUD1	GSM4909302	Human	Breast	IDC	7.51e-14	-5.30e-01	0.1545
9709	HERPUD1	GSM4909304	Human	Breast	IDC	6.31e-03	-3.33e-01	0.1636
9709	HERPUD1	GSM4909307	Human	Breast	IDC	1.55e-13	-5.05e-01	0.1569
9709	HERPUD1	GSM4909308	Human	Breast	IDC	2.95e-04	-3.58e-01	0.158
9709	HERPUD1	GSM4909309	Human	Breast	IDC	9.60e-05	-3.90e-01	0.0483
9709	HERPUD1	GSM4909311	Human	Breast	IDC	4.78e-31	-5.15e-01	0.1534
9709	HERPUD1	GSM4909312	Human	Breast	IDC	5.72e-09	-6.08e-02	0.1552
9709	HERPUD1	GSM4909319	Human	Breast	IDC	8.85e-42	-5.16e-01	0.1563
9709	HERPUD1	GSM4909320	Human	Breast	IDC	5.15e-05	-5.17e-01	0.1575
9709	HERPUD1	GSM4909321	Human	Breast	IDC	1.60e-13	-2.32e-01	0.1559
9709	HERPUD1	M1	Human	Breast	IDC	1.16e-03	-3.91e-01	0.1577
9709	HERPUD1	NCCBC14	Human	Breast	DCIS	2.30e-10	-2.08e-01	0.2021
9709	HERPUD1	NCCBC2	Human	Breast	DCIS	1.48e-02	-3.51e-01	0.1554
9709	HERPUD1	NCCBC3	Human	Breast	DCIS	1.95e-07	2.88e-01	0.1198
9709	HERPUD1	NCCBC5	Human	Breast	DCIS	5.20e-16	-3.68e-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:19018001	Colorectum	SER	positive regulation of proteasomal protein catabolic process	38/2897	114/18723	1.65e-06	7.23e-05	38
GO:00458611	Colorectum	SER	negative regulation of proteolysis	88/2897	351/18723	1.74e-06	7.50e-05	88
GO:00324361	Colorectum	SER	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	32/2897	90/18723	2.23e-06	9.31e-05	32
GO:00525481	Colorectum	SER	regulation of endopeptidase activity	103/2897	432/18723	2.86e-06	1.16e-04	103
GO:00700591	Colorectum	SER	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	25/2897	63/18723	2.92e-06	1.18e-04	25
GO:00432811	Colorectum	SER	regulation of cysteine-type endopeptidase activity involved in apoptotic process	57/2897	209/18723	8.08e-06	2.74e-04	57
GO:20001161	Colorectum	SER	regulation of cysteine-type endopeptidase activity	62/2897	235/18723	1.05e-05	3.39e-04	62
GO:00359661	Colorectum	SER	response to topologically incorrect protein	46/2897	159/18723	1.14e-05	3.63e-04	46
GO:00359671	Colorectum	SER	cellular response to topologically incorrect protein	36/2897	116/18723	1.88e-05	5.51e-04	36
GO:00324691	Colorectum	SER	endoplasmic reticulum calcium ion homeostasis	13/2897	25/18723	2.34e-05	6.64e-04	13
GO:00066051	Colorectum	SER	protein targeting	76/2897	314/18723	3.19e-05	8.47e-04	76
GO:19035731	Colorectum	SER	negative regulation of response to endoplasmic reticulum stress	17/2897	44/18723	1.64e-04	3.12e-03	17
GO:00069861	Colorectum	SER	response to unfolded protein	38/2897	137/18723	1.68e-04	3.16e-03	38
GO:19058971	Colorectum	SER	regulation of response to endoplasmic reticulum stress	26/2897	82/18723	1.76e-04	3.28e-03	26
GO:19022361	Colorectum	SER	negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	10/2897	20/18723	3.20e-04	5.15e-03	10
GO:00346201	Colorectum	SER	cellular response to unfolded protein	28/2897	96/18723	4.78e-04	6.89e-03	28
GO:00431541	Colorectum	SER	negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	24/2897	78/18723	5.04e-04	7.16e-03	24
GO:0030970	Colorectum	SER	retrograde protein transport, ER to cytosol	12/2897	29/18723	7.22e-04	9.44e-03	12
GO:1903513	Colorectum	SER	endoplasmic reticulum to cytosol transport	12/2897	29/18723	7.22e-04	9.44e-03	12
GO:0051346	Colorectum	SER	negative regulation of hydrolase activity	82/2897	379/18723	8.19e-04	1.01e-02	82

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0414125	Cervix	HSIL_HPV	Protein processing in endoplasmic reticulum	21/459	174/8465	4.54e-04	3.80e-03	3.07e-03	21
hsa0414135	Cervix	HSIL_HPV	Protein processing in endoplasmic reticulum	21/459	174/8465	4.54e-04	3.80e-03	3.07e-03	21
hsa0414144	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa0414154	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041416	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa041417	Colorectum	MSI-H	Protein processing in endoplasmic reticulum	46/797	174/8465	4.53e-11	9.78e-10	8.19e-10	46
hsa0414127	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414136	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64

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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

HERPUD1

SNV

Missense_Mutation

rs370880807

c.1168G>A

p.Ala390Thr

p.A390T

Q15011

protein_coding

tolerated(0.08)

benign(0.17)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HERPUD1

SNV

Missense_Mutation

rs527424441

c.394N>T

p.Arg132Trp

p.R132W

Q15011

protein_coding

tolerated(0.17)

benign(0.2)

TCGA-E2-A14S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

HERPUD1

insertion

Frame_Shift_Ins

novel

c.1064_1065insTC

p.Val356LeufsTer3

p.V356Lfs*3

Q15011

protein_coding

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HERPUD1

insertion

In_Frame_Ins

novel

c.1066_1067insTAACAGTGTGTTATACCATAAGAACTGGTATGAAGTGGT

p.Val356_Leu357insThrValCysTyrThrIleArgThrGlyMetLysTrpLeu

p.V356_L357insTVCYTIRTGMKWL

Q15011

protein_coding

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HERPUD1

insertion

Nonsense_Mutation

novel

c.1155_1156insAATAAATTAGGAACCTCTTGAATTAT

p.Pro386AsnfsTer7

p.P386Nfs*7

Q15011

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HERPUD1

insertion

Nonsense_Mutation

novel

c.879_880insTAAAATCTCCTTCATGAGATTGCTGTGGACCCAGCAGCCTGTACAGG

p.Met294Ter

p.M294*

Q15011

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

HERPUD1

deletion

Frame_Shift_Del

novel

c.823delT

p.Ser275LeufsTer13

p.S275Lfs*13

Q15011

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

HERPUD1

SNV

Missense_Mutation

novel

c.950A>C

p.Asn317Thr

p.N317T

Q15011

protein_coding

tolerated(0.17)

benign(0.096)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HERPUD1

SNV

Missense_Mutation

c.916G>T

p.Gly306Trp

p.G306W

Q15011

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A2LX-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HERPUD1

SNV

Missense_Mutation

c.886N>A

p.Ala296Thr

p.A296T

Q15011

protein_coding

deleterious(0.05)

possibly_damaging(0.86)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=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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