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: TPST1

Gene summary for TPST1

Gene summary.

Gene information	Species	Human
	Gene symbol	TPST1
	Gene ID	8460
	Gene name	tyrosylprotein sulfotransferase 1
	Gene Alias	TANGO13A
	Cytomap	7q11.21
	Gene Type	protein-coding
	GO ID	GO:0006082
	UniProtAcc	A0A024RDK9

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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
8460	TPST1	CCI_1	Human	Cervix	CC	7.17e-12	1.17e+00	0.528
8460	TPST1	CCI_2	Human	Cervix	CC	3.38e-03	5.33e-01	0.5249
8460	TPST1	CCI_3	Human	Cervix	CC	1.73e-09	1.02e+00	0.516
8460	TPST1	Tumor	Human	Cervix	CC	3.06e-02	1.22e-01	0.1241
8460	TPST1	sample3	Human	Cervix	CC	3.24e-05	1.68e-01	0.1387
8460	TPST1	T3	Human	Cervix	CC	7.89e-04	1.22e-01	0.1389
8460	TPST1	LZE4T	Human	Esophagus	ESCC	1.73e-16	4.13e-01	0.0811
8460	TPST1	LZE7T	Human	Esophagus	ESCC	2.68e-05	2.08e-01	0.0667
8460	TPST1	LZE20T	Human	Esophagus	ESCC	3.25e-11	2.13e-01	0.0662
8460	TPST1	LZE24T	Human	Esophagus	ESCC	3.08e-10	2.76e-01	0.0596
8460	TPST1	LZE21T	Human	Esophagus	ESCC	6.63e-05	2.56e-01	0.0655
8460	TPST1	P1T-E	Human	Esophagus	ESCC	2.37e-06	3.54e-01	0.0875
8460	TPST1	P2T-E	Human	Esophagus	ESCC	1.32e-33	6.69e-01	0.1177
8460	TPST1	P4T-E	Human	Esophagus	ESCC	3.44e-20	4.25e-01	0.1323
8460	TPST1	P5T-E	Human	Esophagus	ESCC	1.48e-13	3.52e-01	0.1327
8460	TPST1	P8T-E	Human	Esophagus	ESCC	3.23e-09	1.21e-01	0.0889
8460	TPST1	P9T-E	Human	Esophagus	ESCC	9.33e-09	2.11e-01	0.1131
8460	TPST1	P10T-E	Human	Esophagus	ESCC	4.73e-13	2.56e-01	0.116
8460	TPST1	P11T-E	Human	Esophagus	ESCC	1.71e-21	7.46e-01	0.1426
8460	TPST1	P12T-E	Human	Esophagus	ESCC	1.98e-56	1.13e+00	0.1122

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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
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
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:000616318	Prostate	BPH	purine nucleotide metabolic process	109/3107	396/18723	2.28e-08	6.94e-07	109
GO:001969317	Prostate	BPH	ribose phosphate metabolic process	109/3107	396/18723	2.28e-08	6.94e-07	109
GO:007252118	Prostate	BPH	purine-containing compound metabolic process	113/3107	416/18723	2.77e-08	8.13e-07	113
GO:000911717	Prostate	BPH	nucleotide metabolic process	118/3107	489/18723	9.68e-06	1.35e-04	118
GO:000675316	Prostate	BPH	nucleoside phosphate metabolic process	118/3107	497/18723	2.13e-05	2.58e-04	118
GO:001969327	Thyroid	PTC	ribose phosphate metabolic process	176/5968	396/18723	8.28e-08	1.70e-06	176
GO:000915028	Thyroid	PTC	purine ribonucleotide metabolic process	165/5968	368/18723	1.03e-07	2.05e-06	165
GO:007252127	Thyroid	PTC	purine-containing compound metabolic process	182/5968	416/18723	1.92e-07	3.51e-06	182
GO:000925927	Thyroid	PTC	ribonucleotide metabolic process	170/5968	385/18723	2.32e-07	4.08e-06	170
GO:000616327	Thyroid	PTC	purine nucleotide metabolic process	170/5968	396/18723	2.02e-06	2.75e-05	170
GO:000675325	Thyroid	PTC	nucleoside phosphate metabolic process	205/5968	497/18723	5.24e-06	6.35e-05	205
GO:000911725	Thyroid	PTC	nucleotide metabolic process	202/5968	489/18723	5.46e-06	6.60e-05	202
GO:00182126	Thyroid	PTC	peptidyl-tyrosine modification	142/5968	378/18723	1.02e-02	4.14e-02	142
GO:001969328	Thyroid	ATC	ribose phosphate metabolic process	184/6293	396/18723	5.87e-08	1.05e-06	184
GO:000915029	Thyroid	ATC	purine ribonucleotide metabolic process	172/6293	368/18723	9.58e-08	1.64e-06	172
GO:000925928	Thyroid	ATC	ribonucleotide metabolic process	178/6293	385/18723	1.47e-07	2.39e-06	178
GO:007252128	Thyroid	ATC	purine-containing compound metabolic process	189/6293	416/18723	2.83e-07	4.29e-06	189
GO:0006753111	Thyroid	ATC	nucleoside phosphate metabolic process	219/6293	497/18723	5.92e-07	8.29e-06	219
GO:0009117112	Thyroid	ATC	nucleotide metabolic process	215/6293	489/18723	9.09e-07	1.20e-05	215
GO:000616328	Thyroid	ATC	purine nucleotide metabolic process	177/6293	396/18723	2.39e-06	2.82e-05	177

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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

TPST1

SNV

Missense_Mutation

novel

c.862G>C

p.Asp288His

p.D288H

O60507

protein_coding

deleterious(0)

probably_damaging(0.933)

TCGA-A2-A4RW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TPST1

SNV

Missense_Mutation

novel

c.896N>C

p.Leu299Pro

p.L299P

O60507

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1Y0-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide+methotrexatum+fluorouracillum

TPST1

SNV

Missense_Mutation

novel

c.97C>T

p.His33Tyr

p.H33Y

O60507

protein_coding

tolerated_low_confidence(0.88)

benign(0.067)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

TPST1

insertion

Frame_Shift_Ins

novel

c.830_831insGCCTTCCTGTATTATGGAGGGTAATCCACTTTACT

p.Val278ProfsTer12

p.V278Pfs*12

O60507

protein_coding

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

TPST1

SNV

Missense_Mutation

c.1099N>A

p.Glu367Lys

p.E367K

O60507

protein_coding

tolerated_low_confidence(0.81)

benign(0)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TPST1

SNV

Missense_Mutation

rs752674832

c.202G>T

p.Asp68Tyr

p.D68Y

O60507

protein_coding

tolerated(0.22)

benign(0.009)

TCGA-AA-3977-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TPST1

SNV

Missense_Mutation

novel

c.226N>T

p.Gly76Cys

p.G76C

O60507

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AA-A01D-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

capecitabine

TPST1

SNV

Missense_Mutation

c.17N>C

p.Lys6Thr

p.K6T

O60507

protein_coding

tolerated_low_confidence(0.07)

possibly_damaging(0.731)

TCGA-AM-5821-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TPST1

SNV

Missense_Mutation

rs866156741

c.101N>A

p.Arg34Gln

p.R34Q

O60507

protein_coding

tolerated_low_confidence(0.53)

benign(0.277)

TCGA-D5-6530-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

TPST1

SNV

Missense_Mutation

c.83C>T

p.Ala28Val

p.A28V

O60507

protein_coding

tolerated_low_confidence(0.73)

benign(0.015)

TCGA-D5-6928-01

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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