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: TRIR

Gene summary for TRIR

Gene summary.

Gene information	Species	Human
	Gene symbol	TRIR
	Gene ID	79002
	Gene name	telomerase RNA component interacting RNase
	Gene Alias	C19orf43
	Cytomap	19p13.13
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	K7EN60

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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
79002	TRIR	GSM5353215_PA_AUG_PB_1B_S2	Human	Prostate	Tumor	6.15e-06	-8.20e-01	0.1557
79002	TRIR	GSM5353216_PA_PB1A_Pool_1_3_S50_L002	Human	Prostate	Tumor	5.12e-05	-8.20e-01	0.159
79002	TRIR	GSM5353217_PA_PB1A_Pool_2_S107_L004	Human	Prostate	Tumor	3.64e-02	-8.20e-01	0.156
79002	TRIR	GSM5353218_PA_PB1B_Pool_1_2_S74_L003	Human	Prostate	Tumor	9.11e-04	-8.20e-01	0.1479
79002	TRIR	GSM5353220_PA_PB1B_Pool_3_S51_L002	Human	Prostate	Tumor	5.12e-05	-8.20e-01	0.1531
79002	TRIR	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	7.05e-20	-8.20e-01	0.1633
79002	TRIR	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	8.48e-28	-8.20e-01	0.1608
79002	TRIR	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	7.53e-17	-8.20e-01	0.1604
79002	TRIR	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	3.97e-18	-8.20e-01	0.1621
79002	TRIR	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	1.72e-09	-8.20e-01	0.1619
79002	TRIR	GSM5353226_PA_PR5196-2_Pool_1_2_3_S54_L002	Human	Prostate	Tumor	6.15e-06	-8.20e-01	0.159
79002	TRIR	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	7.37e-21	-8.20e-01	0.1602
79002	TRIR	GSM5353228_PA_PR5199-640K_Pool_1_3_S108_L004	Human	Prostate	Tumor	8.22e-03	-8.20e-01	0.1537
79002	TRIR	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	1.05e-04	-8.20e-01	0.1439
79002	TRIR	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	2.37e-10	-8.20e-01	0.1608
79002	TRIR	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	6.15e-06	-8.20e-01	0.1622
79002	TRIR	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	7.39e-32	-8.20e-01	0.1575
79002	TRIR	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	6.65e-35	-8.20e-01	0.1545
79002	TRIR	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	3.91e-27	-8.20e-01	0.1569
79002	TRIR	GSM5353247_PA_PR5269_3_S27_L002	Human	Prostate	Tumor	3.64e-02	-8.20e-01	0.1532

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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
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:00160726	Breast	Precancer	rRNA metabolic process	36/1080	236/18723	8.59e-08	4.84e-06	36
GO:00064018	Breast	Precancer	RNA catabolic process	34/1080	278/18723	2.88e-05	6.39e-04	34
GO:00346558	Breast	Precancer	nucleobase-containing compound catabolic process	42/1080	407/18723	1.91e-04	3.06e-03	42
GO:00467007	Breast	Precancer	heterocycle catabolic process	44/1080	445/18723	3.49e-04	4.88e-03	44
GO:00442708	Breast	Precancer	cellular nitrogen compound catabolic process	44/1080	451/18723	4.64e-04	6.12e-03	44
GO:00194397	Breast	Precancer	aromatic compound catabolic process	44/1080	467/18723	9.55e-04	1.07e-02	44
GO:00346604	Breast	Precancer	ncRNA metabolic process	45/1080	485/18723	1.15e-03	1.26e-02	45
GO:19013617	Breast	Precancer	organic cyclic compound catabolic process	45/1080	495/18723	1.73e-03	1.74e-02	45
GO:001607214	Breast	IDC	rRNA metabolic process	36/1434	236/18723	5.48e-05	1.17e-03	36
GO:000640113	Breast	IDC	RNA catabolic process	38/1434	278/18723	3.54e-04	5.16e-03	38
GO:190136112	Breast	IDC	organic cyclic compound catabolic process	56/1434	495/18723	2.12e-03	1.99e-02	56
GO:004670012	Breast	IDC	heterocycle catabolic process	51/1434	445/18723	2.51e-03	2.25e-02	51
GO:003465513	Breast	IDC	nucleobase-containing compound catabolic process	47/1434	407/18723	3.12e-03	2.63e-02	47
GO:004427012	Breast	IDC	cellular nitrogen compound catabolic process	50/1434	451/18723	5.29e-03	3.93e-02	50
GO:001943912	Breast	IDC	aromatic compound catabolic process	51/1434	467/18723	6.54e-03	4.59e-02	51
GO:001607222	Breast	DCIS	rRNA metabolic process	36/1390	236/18723	2.86e-05	6.42e-04	36
GO:000640123	Breast	DCIS	RNA catabolic process	38/1390	278/18723	1.91e-04	3.08e-03	38
GO:003465522	Breast	DCIS	nucleobase-containing compound catabolic process	47/1390	407/18723	1.69e-03	1.68e-02	47
GO:190136122	Breast	DCIS	organic cyclic compound catabolic process	55/1390	495/18723	1.75e-03	1.71e-02	55
GO:004670022	Breast	DCIS	heterocycle catabolic process	50/1390	445/18723	2.19e-03	2.03e-02	50

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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

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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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