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: TIPRL

Gene summary for TIPRL

Gene summary.

Gene information	Species	Human
	Gene symbol	TIPRL
	Gene ID	261726
	Gene name	TOR signaling pathway regulator
	Gene Alias	TIP
	Cytomap	1q24.2
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	O75663

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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
261726	TIPRL	P47T-E	Human	Esophagus	ESCC	3.54e-47	8.29e-01	0.1067
261726	TIPRL	P48T-E	Human	Esophagus	ESCC	1.10e-22	4.56e-01	0.0959
261726	TIPRL	P49T-E	Human	Esophagus	ESCC	8.09e-26	2.28e+00	0.1768
261726	TIPRL	P52T-E	Human	Esophagus	ESCC	3.26e-44	9.57e-01	0.1555
261726	TIPRL	P54T-E	Human	Esophagus	ESCC	1.21e-23	5.01e-01	0.0975
261726	TIPRL	P56T-E	Human	Esophagus	ESCC	2.30e-12	1.62e+00	0.1613
261726	TIPRL	P57T-E	Human	Esophagus	ESCC	2.19e-16	3.43e-01	0.0926
261726	TIPRL	P61T-E	Human	Esophagus	ESCC	2.02e-20	4.14e-01	0.099
261726	TIPRL	P62T-E	Human	Esophagus	ESCC	2.28e-71	1.15e+00	0.1302
261726	TIPRL	P65T-E	Human	Esophagus	ESCC	3.45e-31	5.50e-01	0.0978
261726	TIPRL	P74T-E	Human	Esophagus	ESCC	1.44e-44	1.19e+00	0.1479
261726	TIPRL	P75T-E	Human	Esophagus	ESCC	2.47e-60	1.06e+00	0.1125
261726	TIPRL	P76T-E	Human	Esophagus	ESCC	5.11e-64	1.11e+00	0.1207
261726	TIPRL	P79T-E	Human	Esophagus	ESCC	2.17e-36	5.89e-01	0.1154
261726	TIPRL	P80T-E	Human	Esophagus	ESCC	4.64e-54	1.63e+00	0.155
261726	TIPRL	P82T-E	Human	Esophagus	ESCC	8.62e-18	1.11e+00	0.1072
261726	TIPRL	P83T-E	Human	Esophagus	ESCC	9.19e-52	1.47e+00	0.1738
261726	TIPRL	P84T-E	Human	Esophagus	ESCC	3.54e-16	6.65e-01	0.0933
261726	TIPRL	P89T-E	Human	Esophagus	ESCC	8.07e-32	2.10e+00	0.1752
261726	TIPRL	P91T-E	Human	Esophagus	ESCC	3.88e-19	1.95e+00	0.1828

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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
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
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:005134613	Breast	IDC	negative regulation of hydrolase activity	71/1434	379/18723	1.33e-12	2.90e-10	71
GO:003530414	Breast	IDC	regulation of protein dephosphorylation	18/1434	90/18723	1.39e-04	2.48e-03	18
GO:00459369	Breast	IDC	negative regulation of phosphate metabolic process	53/1434	441/18723	7.21e-04	8.79e-03	53
GO:00105639	Breast	IDC	negative regulation of phosphorus metabolic process	53/1434	442/18723	7.60e-04	9.25e-03	53
GO:003530813	Breast	IDC	negative regulation of protein dephosphorylation	9/1434	34/18723	8.01e-04	9.58e-03	9
GO:004366613	Breast	IDC	regulation of phosphoprotein phosphatase activity	12/1434	58/18723	1.27e-03	1.35e-02	12
GO:00353052	Breast	IDC	negative regulation of dephosphorylation	9/1434	45/18723	6.33e-03	4.47e-02	9
GO:005134623	Breast	DCIS	negative regulation of hydrolase activity	64/1390	379/18723	4.32e-10	4.80e-08	64
GO:003530423	Breast	DCIS	regulation of protein dephosphorylation	18/1390	90/18723	9.33e-05	1.71e-03	18
GO:004593614	Breast	DCIS	negative regulation of phosphate metabolic process	53/1390	441/18723	3.48e-04	4.96e-03	53
GO:001056314	Breast	DCIS	negative regulation of phosphorus metabolic process	53/1390	442/18723	3.68e-04	5.18e-03	53
GO:003530821	Breast	DCIS	negative regulation of protein dephosphorylation	9/1390	34/18723	6.39e-04	7.92e-03	9
GO:004366622	Breast	DCIS	regulation of phosphoprotein phosphatase activity	12/1390	58/18723	9.71e-04	1.08e-02	12
GO:003530511	Breast	DCIS	negative regulation of dephosphorylation	9/1390	45/18723	5.17e-03	3.81e-02	9
GO:00353039	Breast	DCIS	regulation of dephosphorylation	18/1390	128/18723	6.44e-03	4.58e-02	18
GO:004593626	Esophagus	HGIN	negative regulation of phosphate metabolic process	89/2587	441/18723	1.24e-04	2.54e-03	89
GO:001056326	Esophagus	HGIN	negative regulation of phosphorus metabolic process	89/2587	442/18723	1.34e-04	2.71e-03	89
GO:000647017	Esophagus	HGIN	protein dephosphorylation	61/2587	281/18723	1.86e-04	3.51e-03	61
GO:003530425	Esophagus	HGIN	regulation of protein dephosphorylation	24/2587	90/18723	9.27e-04	1.17e-02	24
GO:00427708	Esophagus	HGIN	signal transduction in response to DNA damage	39/2587	172/18723	1.07e-03	1.32e-02	39

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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

TIPRL

insertion

Frame_Shift_Ins

novel

c.751_752insAC

p.Lys251AsnfsTer3

p.K251Nfs*3

O75663

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TIPRL

insertion

In_Frame_Ins

novel

c.753_754insCTCAAGCCTTGT

p.Leu252_Ile253insLysProCysLeu

p.L252_I253insKPCL

O75663

protein_coding

TCGA-A2-A04Y-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TIPRL

SNV

Missense_Mutation

rs760294386

c.215C>T

p.Ala72Val

p.A72V

O75663

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TIPRL

SNV

Missense_Mutation

novel

c.277N>A

p.Glu93Lys

p.E93K

O75663

protein_coding

deleterious(0.03)

benign(0.356)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

TIPRL

SNV

Missense_Mutation

novel

c.201C>A

p.Phe67Leu

p.F67L

O75663

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

TIPRL

SNV

Missense_Mutation

novel

c.371C>T

p.Ser124Phe

p.S124F

O75663

protein_coding

deleterious(0.02)

benign(0.353)

TCGA-AX-A1CE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

TIPRL

SNV

Missense_Mutation

novel

c.491N>A

p.Gly164Glu

p.G164E

O75663

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

TIPRL

SNV

Missense_Mutation

novel

c.593A>G

p.Asp198Gly

p.D198G

O75663

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-FI-A2D5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatinum

TIPRL

SNV

Missense_Mutation

c.519N>C

p.Arg173Ser

p.R173S

O75663

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-DD-A73C-01

Liver

liver hepatocellular carcinoma

Female

>=65

III/IV

Unknown

TIPRL

SNV

Missense_Mutation

c.94N>T

p.Asp32Tyr

p.D32Y

O75663

protein_coding

tolerated(0.09)

possibly_damaging(0.62)

TCGA-44-7669-01

Lung

lung adenocarcinoma

Male

<65

I/II

Chemotherapy

alimta

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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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