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: TXK

Gene summary for TXK

Gene summary.

Gene information	Species	Human
	Gene symbol	TXK
	Gene ID	7294
	Gene name	TXK tyrosine kinase
	Gene Alias	BTKL
	Cytomap	4p12
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	P42681

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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
7294	TXK	AEH-subject1	Human	Endometrium	AEH	1.92e-03	2.39e-01	-0.3059
7294	TXK	AEH-subject3	Human	Endometrium	AEH	1.53e-03	2.61e-01	-0.2576
7294	TXK	AEH-subject5	Human	Endometrium	AEH	2.21e-25	6.75e-01	-0.2953
7294	TXK	EEC-subject1	Human	Endometrium	EEC	3.54e-19	5.74e-01	-0.2682
7294	TXK	EEC-subject2	Human	Endometrium	EEC	7.62e-03	2.04e-01	-0.2607
7294	TXK	EEC-subject4	Human	Endometrium	EEC	2.34e-12	4.04e-01	-0.2571
7294	TXK	EEC-subject5	Human	Endometrium	EEC	2.46e-20	5.33e-01	-0.249

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Endometrium		AEH: Atypical endometrial hyperplasia
Endometrium		EEC: Endometrioid 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:004206016	Endometrium	AEH	wound healing	91/2100	422/18723	4.85e-10	4.61e-08	91
GO:00072296	Endometrium	AEH	integrin-mediated signaling pathway	32/2100	107/18723	1.24e-07	5.80e-06	32
GO:00310997	Endometrium	AEH	regeneration	41/2100	198/18723	7.29e-05	1.11e-03	41
GO:00075967	Endometrium	AEH	blood coagulation	43/2100	217/18723	1.42e-04	1.89e-03	43
GO:00075997	Endometrium	AEH	hemostasis	43/2100	222/18723	2.39e-04	2.86e-03	43
GO:00508177	Endometrium	AEH	coagulation	43/2100	222/18723	2.39e-04	2.86e-03	43
GO:005087815	Endometrium	AEH	regulation of body fluid levels	64/2100	379/18723	5.40e-04	5.44e-03	64
GO:00027645	Endometrium	AEH	immune response-regulating signaling pathway	76/2100	468/18723	5.76e-04	5.71e-03	76
GO:00508525	Endometrium	AEH	T cell receptor signaling pathway	26/2100	123/18723	1.03e-03	9.15e-03	26
GO:00321036	Endometrium	AEH	positive regulation of response to external stimulus	68/2100	427/18723	1.82e-03	1.44e-02	68
GO:00301683	Endometrium	AEH	platelet activation	25/2100	123/18723	2.26e-03	1.74e-02	25
GO:00018198	Endometrium	AEH	positive regulation of cytokine production	71/2100	467/18723	4.76e-03	3.02e-02	71
GO:004206017	Endometrium	EEC	wound healing	92/2168	422/18723	1.12e-09	9.58e-08	92
GO:000722914	Endometrium	EEC	integrin-mediated signaling pathway	32/2168	107/18723	2.58e-07	1.10e-05	32
GO:003109914	Endometrium	EEC	regeneration	45/2168	198/18723	6.19e-06	1.49e-04	45
GO:000759613	Endometrium	EEC	blood coagulation	44/2168	217/18723	1.42e-04	1.84e-03	44
GO:000276412	Endometrium	EEC	immune response-regulating signaling pathway	80/2168	468/18723	2.20e-04	2.64e-03	80
GO:000759913	Endometrium	EEC	hemostasis	44/2168	222/18723	2.43e-04	2.85e-03	44
GO:005081713	Endometrium	EEC	coagulation	44/2168	222/18723	2.43e-04	2.85e-03	44
GO:005087816	Endometrium	EEC	regulation of body fluid levels	65/2168	379/18723	7.48e-04	7.05e-03	65

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0467026	Endometrium	AEH	Leukocyte transendothelial migration	37/1197	114/8465	4.51e-07	6.11e-06	4.47e-06	37
hsa04670111	Endometrium	AEH	Leukocyte transendothelial migration	37/1197	114/8465	4.51e-07	6.11e-06	4.47e-06	37
hsa0467027	Endometrium	EEC	Leukocyte transendothelial migration	36/1237	114/8465	2.97e-06	3.91e-05	2.91e-05	36
hsa0467036	Endometrium	EEC	Leukocyte transendothelial migration	36/1237	114/8465	2.97e-06	3.91e-05	2.91e-05	36

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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

TXK

SNV

Missense_Mutation

c.1276G>A

p.Ala426Thr

p.A426T

P42681

protein_coding

tolerated(1)

benign(0.391)

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

TXK

SNV

Missense_Mutation

c.1290C>G

p.Ile430Met

p.I430M

P42681

protein_coding

deleterious(0.01)

possibly_damaging(0.653)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TXK

insertion

Nonsense_Mutation

novel

c.391_392insAAGTAGAGACAGAGTTTCAC

p.Leu131Ter

p.L131*

P42681

protein_coding

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

TXK

insertion

Nonsense_Mutation

novel

c.744_745insTTACATTACCAGGAGCCTTAATCTTCACCCTTTTGATAAATTA

p.Met249LeufsTer7

p.M249Lfs*7

P42681

protein_coding

TCGA-B6-A0IE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TXK

insertion

Frame_Shift_Ins

novel

c.1577_1578insG

p.Trp527LeufsTer21

p.W527Lfs*21

P42681

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

TXK

insertion

Nonsense_Mutation

novel

c.1576_1577insGCTAGGTGTAGTGGTGCATGCATGCA

p.Thr526SerfsTer2

p.T526Sfs*2

P42681

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

TXK

SNV

Missense_Mutation

novel

c.1556N>G

p.Ala519Gly

p.A519G

P42681

protein_coding

tolerated(0.34)

benign(0.005)

TCGA-C5-A3HD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TXK

SNV

Missense_Mutation

novel

c.1384G>A

p.Glu462Lys

p.E462K

P42681

protein_coding

tolerated(0.1)

probably_damaging(0.978)

TCGA-C5-A8YR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

TXK

SNV

Missense_Mutation

c.1439N>G

p.Ser480Cys

p.S480C

P42681

protein_coding

deleterious(0.02)

probably_damaging(0.974)

TCGA-IR-A3LH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TXK

SNV

Missense_Mutation

novel

c.656A>T

p.His219Leu

p.H219L

P42681

protein_coding

deleterious(0.02)

probably_damaging(0.938)

TCGA-PN-A8MA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	178102336	BOSUTINIB
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	249565828
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	HESPERADIN	HESPERADIN	19035792
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	318164804
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	354702234
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	178103494	IBRUTINIB
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	249565852
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	249565825
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	310264693	ACALABRUTINIB
7294	TXK	KINASE, TRANSCRIPTION FACTOR, DRUGGABLE GENOME, TYROSINE KINASE, ENZYME	inhibitor	249565826

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