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: HRH1

Gene summary for HRH1

Gene summary.

Gene information	Species	Human
	Gene symbol	HRH1
	Gene ID	3269
	Gene name	histamine receptor H1
	Gene Alias	H1-R
	Cytomap	3p25.3
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	P35367

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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
3269	HRH1	CCI_1	Human	Cervix	CC	4.16e-07	9.32e-01	0.528
3269	HRH1	CCI_2	Human	Cervix	CC	8.79e-05	7.78e-01	0.5249
3269	HRH1	CCI_3	Human	Cervix	CC	6.20e-03	2.42e-01	0.516
3269	HRH1	T2	Human	Cervix	CC	1.74e-03	3.07e-01	0.0709
3269	HRH1	HTA11_1938_2000001011	Human	Colorectum	AD	1.83e-03	4.26e-01	-0.0811
3269	HRH1	HTA11_347_2000001011	Human	Colorectum	AD	2.93e-10	5.00e-01	-0.1954
3269	HRH1	HTA11_83_2000001011	Human	Colorectum	SER	1.01e-02	4.40e-01	-0.1526
3269	HRH1	HTA11_696_2000001011	Human	Colorectum	AD	2.81e-04	3.53e-01	-0.1464
3269	HRH1	HTA11_866_2000001011	Human	Colorectum	AD	1.47e-05	3.47e-01	-0.1001
3269	HRH1	HTA11_1391_2000001011	Human	Colorectum	AD	9.91e-03	3.59e-01	-0.059
3269	HRH1	HTA11_99999971662_82457	Human	Colorectum	MSS	4.16e-02	2.78e-01	0.3859
3269	HRH1	A015-C-006	Human	Colorectum	FAP	3.48e-03	-1.55e-01	-0.0994
3269	HRH1	A015-C-104	Human	Colorectum	FAP	3.97e-02	-6.92e-02	-0.1899
3269	HRH1	RNA-P17T-P17T-4	Human	Lung	IAC	4.71e-02	3.93e-01	0.343
3269	HRH1	RNA-P17T-P17T-8	Human	Lung	IAC	1.55e-04	4.91e-01	0.3329
3269	HRH1	RNA-P25T1-P25T1-1	Human	Lung	AIS	8.87e-03	2.36e-01	-0.2116
3269	HRH1	RNA-P6T2-P6T2-2	Human	Lung	IAC	1.06e-02	1.72e-01	-0.0132
3269	HRH1	RNA-P6T2-P6T2-4	Human	Lung	IAC	6.25e-03	1.75e-01	-0.0121
3269	HRH1	RNA-P7T1-P7T1-1	Human	Lung	AIS	7.48e-05	5.08e-01	-0.0961
3269	HRH1	RNA-P7T1-P7T1-2	Human	Lung	AIS	2.28e-04	5.41e-01	-0.0876

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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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00603267	Cervix	CC	cell chemotaxis	73/2311	310/18723	2.82e-08	1.96e-06	73
GO:00975298	Cervix	CC	myeloid leukocyte migration	56/2311	220/18723	7.21e-08	4.15e-06	56
GO:00305957	Cervix	CC	leukocyte chemotaxis	57/2311	230/18723	1.48e-07	7.07e-06	57
GO:00716218	Cervix	CC	granulocyte chemotaxis	37/2311	125/18723	2.16e-07	9.56e-06	37
GO:00509007	Cervix	CC	leukocyte migration	78/2311	369/18723	1.09e-06	3.80e-05	78
GO:00975308	Cervix	CC	granulocyte migration	39/2311	148/18723	2.67e-06	7.87e-05	39
GO:00093149	Cervix	CC	response to radiation	86/2311	456/18723	3.50e-05	5.63e-04	86
GO:00094163	Cervix	CC	response to light stimulus	54/2311	320/18723	1.03e-02	4.97e-02	54
GO:0006066	Colorectum	AD	alcohol metabolic process	106/3918	353/18723	3.02e-05	5.57e-04	106
GO:0044262	Colorectum	AD	cellular carbohydrate metabolic process	87/3918	283/18723	6.00e-05	1.01e-03	87
GO:0006109	Colorectum	AD	regulation of carbohydrate metabolic process	55/3918	178/18723	1.10e-03	1.01e-02	55
GO:0062012	Colorectum	AD	regulation of small molecule metabolic process	93/3918	334/18723	1.46e-03	1.24e-02	93
GO:00060661	Colorectum	SER	alcohol metabolic process	79/2897	353/18723	3.50e-04	5.50e-03	79
GO:00060662	Colorectum	MSS	alcohol metabolic process	92/3467	353/18723	2.57e-04	3.46e-03	92
GO:00620121	Colorectum	MSS	regulation of small molecule metabolic process	83/3467	334/18723	2.25e-03	1.85e-02	83
GO:00061091	Colorectum	MSS	regulation of carbohydrate metabolic process	47/3467	178/18723	5.75e-03	3.90e-02	47
GO:0062013	Colorectum	MSS	positive regulation of small molecule metabolic process	39/3467	143/18723	6.34e-03	4.23e-02	39
GO:00442621	Colorectum	FAP	cellular carbohydrate metabolic process	66/2622	283/18723	1.53e-05	4.01e-04	66
GO:00061092	Colorectum	FAP	regulation of carbohydrate metabolic process	46/2622	178/18723	1.99e-05	4.90e-04	46
GO:00620122	Colorectum	FAP	regulation of small molecule metabolic process	74/2622	334/18723	3.15e-05	7.13e-04	74

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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

HRH1

SNV

Missense_Mutation

rs773371879

c.434C>T

p.Ser145Leu

p.S145L

P35367

protein_coding

tolerated(0.18)

probably_damaging(0.931)

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

HRH1

SNV

Missense_Mutation

c.616N>G

p.Met206Val

p.M206V

P35367

protein_coding

deleterious(0)

possibly_damaging(0.472)

TCGA-D8-A1XY-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

tamoxiphen

HRH1

SNV

Missense_Mutation

novel

c.916G>A

p.Asp306Asn

p.D306N

P35367

protein_coding

tolerated(0.49)

benign(0)

TCGA-D8-A73U-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

HRH1

insertion

Frame_Shift_Ins

novel

c.102_103insTTAGGTTTAGGTCCCACTTCTAAATTTACCA

p.Ser35LeufsTer31

p.S35Lfs*31

P35367

protein_coding

TCGA-A8-A093-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

HRH1

insertion

Nonsense_Mutation

novel

c.412_413insCCTAGAAGAGTGACAGAAATTCAATAAATAGTTGTTAAGTGAGCAA

p.Tyr138SerfsTer2

p.Y138Sfs*2

P35367

protein_coding

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

HRH1

SNV

Missense_Mutation

c.1299N>G

p.Ile433Met

p.I433M

P35367

protein_coding

deleterious(0)

probably_damaging(0.947)

TCGA-C5-A7UH-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

HRH1

SNV

Missense_Mutation

c.835A>T

p.Thr279Ser

p.T279S

P35367

protein_coding

tolerated(0.73)

benign(0)

TCGA-WL-A834-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

paclitaxel

HRH1

SNV

Missense_Mutation

rs138501310

c.1187C>T

p.Ser396Leu

p.S396L

P35367

protein_coding

deleterious(0.03)

possibly_damaging(0.559)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

HRH1

SNV

Missense_Mutation

c.469C>A

p.Leu157Met

p.L157M

P35367

protein_coding

tolerated(0.59)

possibly_damaging(0.484)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

HRH1

SNV

Missense_Mutation

rs370754604

c.226N>A

p.Val76Met

p.V76M

P35367

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AD-5900-01

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
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME	antagonist	135650208	DOXEPIN
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME		BROMODIPHENHYDRAMINE	BROMODIPHENHYDRAMINE
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME		PHENIRAMINE	PHENIRAMINE
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME	antagonist	135650867	PYRILAMINE
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME		Phenindamine	PHENINDAMINE
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME		BIPERIDEN	BIPERIDEN	22793499
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME	antagonist	178103781	KETOTIFEN
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME	antagonist	CHEMBL1201007	HYDROXYZINE HYDROCHLORIDE
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME	antagonist	135650435
3269	HRH1	G PROTEIN COUPLED RECEPTOR, DRUGGABLE GENOME	agonist	135649684

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