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: TPST2

Gene summary for TPST2

Gene summary.

Gene information	Species	Human
	Gene symbol	TPST2
	Gene ID	8459
	Gene name	tyrosylprotein sulfotransferase 2
	Gene Alias	TANGO13B
	Cytomap	22q12.1
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	A0A024R1G9

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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
8459	TPST2	HTA11_78_2000001011	Human	Colorectum	AD	1.40e-03	2.56e-01	-0.1088
8459	TPST2	HTA11_347_2000001011	Human	Colorectum	AD	3.71e-11	4.10e-01	-0.1954
8459	TPST2	HTA11_1391_2000001011	Human	Colorectum	AD	5.68e-06	3.56e-01	-0.059
8459	TPST2	HTA11_546_2000001011	Human	Colorectum	AD	1.33e-02	3.06e-01	-0.0842
8459	TPST2	HTA11_99999965104_69814	Human	Colorectum	MSS	1.43e-37	1.59e+00	0.281
8459	TPST2	HTA11_99999971662_82457	Human	Colorectum	MSS	1.52e-10	4.94e-01	0.3859
8459	TPST2	A002-C-116	Human	Colorectum	FAP	4.03e-02	-4.62e-02	-0.0452
8459	TPST2	LZE4T	Human	Esophagus	ESCC	5.49e-05	2.65e-01	0.0811
8459	TPST2	LZE7T	Human	Esophagus	ESCC	1.54e-07	2.05e-01	0.0667
8459	TPST2	LZE8T	Human	Esophagus	ESCC	2.50e-09	4.19e-01	0.067
8459	TPST2	LZE22T	Human	Esophagus	ESCC	3.85e-02	1.72e-01	0.068
8459	TPST2	LZE24T	Human	Esophagus	ESCC	4.65e-15	3.88e-01	0.0596
8459	TPST2	LZE21T	Human	Esophagus	ESCC	5.28e-07	3.29e-01	0.0655
8459	TPST2	LZE6T	Human	Esophagus	ESCC	6.25e-07	3.45e-01	0.0845
8459	TPST2	P1T-E	Human	Esophagus	ESCC	9.05e-06	4.91e-01	0.0875
8459	TPST2	P2T-E	Human	Esophagus	ESCC	7.08e-23	7.22e-01	0.1177
8459	TPST2	P4T-E	Human	Esophagus	ESCC	6.56e-12	4.55e-01	0.1323
8459	TPST2	P5T-E	Human	Esophagus	ESCC	6.33e-14	2.46e-01	0.1327
8459	TPST2	P8T-E	Human	Esophagus	ESCC	1.10e-16	2.99e-01	0.0889
8459	TPST2	P9T-E	Human	Esophagus	ESCC	1.72e-12	4.00e-01	0.1131

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0009150	Colorectum	AD	purine ribonucleotide metabolic process	142/3918	368/18723	4.29e-15	1.17e-12	142
GO:0006163	Colorectum	AD	purine nucleotide metabolic process	149/3918	396/18723	1.08e-14	2.80e-12	149
GO:0072521	Colorectum	AD	purine-containing compound metabolic process	153/3918	416/18723	4.34e-14	1.01e-11	153
GO:0009259	Colorectum	AD	ribonucleotide metabolic process	144/3918	385/18723	5.25e-14	1.13e-11	144
GO:0019693	Colorectum	AD	ribose phosphate metabolic process	145/3918	396/18723	3.01e-13	5.71e-11	145
GO:0009117	Colorectum	AD	nucleotide metabolic process	168/3918	489/18723	2.20e-12	3.36e-10	168
GO:0006753	Colorectum	AD	nucleoside phosphate metabolic process	169/3918	497/18723	4.99e-12	6.98e-10	169
GO:0006790	Colorectum	AD	sulfur compound metabolic process	101/3918	339/18723	6.46e-05	1.07e-03	101
GO:0033865	Colorectum	AD	nucleoside bisphosphate metabolic process	42/3918	128/18723	1.12e-03	1.02e-02	42
GO:0033875	Colorectum	AD	ribonucleoside bisphosphate metabolic process	42/3918	128/18723	1.12e-03	1.02e-02	42
GO:0034032	Colorectum	AD	purine nucleoside bisphosphate metabolic process	42/3918	128/18723	1.12e-03	1.02e-02	42
GO:0034035	Colorectum	AD	purine ribonucleoside bisphosphate metabolic process	11/3918	21/18723	1.43e-03	1.22e-02	11
GO:0050427	Colorectum	AD	3'-phosphoadenosine 5'-phosphosulfate metabolic process	11/3918	21/18723	1.43e-03	1.22e-02	11
GO:00061632	Colorectum	MSS	purine nucleotide metabolic process	128/3467	396/18723	2.04e-11	3.02e-09	128
GO:00091502	Colorectum	MSS	purine ribonucleotide metabolic process	121/3467	368/18723	2.08e-11	3.02e-09	121
GO:00725212	Colorectum	MSS	purine-containing compound metabolic process	132/3467	416/18723	4.13e-11	4.86e-09	132
GO:00092592	Colorectum	MSS	ribonucleotide metabolic process	123/3467	385/18723	1.17e-10	1.20e-08	123
GO:00196932	Colorectum	MSS	ribose phosphate metabolic process	124/3467	396/18723	4.11e-10	3.49e-08	124
GO:00091172	Colorectum	MSS	nucleotide metabolic process	144/3467	489/18723	1.87e-09	1.35e-07	144
GO:00067532	Colorectum	MSS	nucleoside phosphate metabolic process	145/3467	497/18723	3.25e-09	2.23e-07	145

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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

TPST2

insertion

Frame_Shift_Ins

rs756080117

c.996_997insC

p.Asn333GlnfsTer6

p.N333Qfs*6

O60704

protein_coding

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TPST2

insertion

Frame_Shift_Ins

novel

c.996_997insCC

p.Asn333ProfsTer18

p.N333Pfs*18

O60704

protein_coding

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TPST2

SNV

Missense_Mutation

novel

c.949N>A

p.Ala317Thr

p.A317T

O60704

protein_coding

deleterious(0.02)

benign(0.421)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TPST2

SNV

Missense_Mutation

novel

c.655N>A

p.Glu219Lys

p.E219K

O60704

protein_coding

tolerated(0.14)

benign(0.094)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TPST2

SNV

Missense_Mutation

rs770653345

c.485N>T

p.Thr162Met

p.T162M

O60704

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TPST2

SNV

Missense_Mutation

novel

c.499N>T

p.Val167Phe

p.V167F

O60704

protein_coding

deleterious(0.03)

possibly_damaging(0.672)

TCGA-LP-A4AW-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TPST2

SNV

Missense_Mutation

c.839C>T

p.Ser280Phe

p.S280F

O60704

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-MY-A5BD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TPST2

SNV

Missense_Mutation

c.391N>A

p.Glu131Lys

p.E131K

O60704

protein_coding

tolerated(0.15)

benign(0.024)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TPST2

SNV

Missense_Mutation

novel

c.281N>C

p.Val94Ala

p.V94A

O60704

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-VS-A9U6-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TPST2

SNV

Missense_Mutation

novel

c.949N>A

p.Ala317Thr

p.A317T

O60704

protein_coding

deleterious(0.02)

benign(0.421)

TCGA-AA-3663-01

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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