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: IBTK

Gene summary for IBTK

Gene summary.

Gene information	Species	Human
	Gene symbol	IBTK
	Gene ID	25998
	Gene name	inhibitor of Bruton tyrosine kinase
	Gene Alias	BTBD26
	Cytomap	6q14.1
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	B7ZLE0

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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
25998	IBTK	HTA11_3410_2000001011	Human	Colorectum	AD	2.10e-09	-5.34e-01	0.0155
25998	IBTK	HTA11_7696_3000711011	Human	Colorectum	AD	2.58e-04	-3.52e-01	0.0674
25998	IBTK	HTA11_6818_2000001021	Human	Colorectum	AD	2.18e-02	-5.09e-01	0.0588
25998	IBTK	HTA11_99999974143_84620	Human	Colorectum	MSS	2.96e-08	-4.65e-01	0.3005
25998	IBTK	A015-C-203	Human	Colorectum	FAP	1.56e-19	-3.51e-01	-0.1294
25998	IBTK	A015-C-204	Human	Colorectum	FAP	1.52e-02	-2.41e-01	-0.0228
25998	IBTK	A014-C-040	Human	Colorectum	FAP	1.97e-02	-3.81e-01	-0.1184
25998	IBTK	A002-C-201	Human	Colorectum	FAP	4.14e-11	-4.04e-01	0.0324
25998	IBTK	A001-C-119	Human	Colorectum	FAP	3.49e-02	-3.40e-01	-0.1557
25998	IBTK	A001-C-108	Human	Colorectum	FAP	1.12e-10	-1.22e-01	-0.0272
25998	IBTK	A002-C-205	Human	Colorectum	FAP	2.00e-15	-3.74e-01	-0.1236
25998	IBTK	A015-C-006	Human	Colorectum	FAP	4.33e-09	-2.94e-01	-0.0994
25998	IBTK	A015-C-106	Human	Colorectum	FAP	6.03e-07	-2.47e-01	-0.0511
25998	IBTK	A002-C-114	Human	Colorectum	FAP	2.11e-12	-3.53e-01	-0.1561
25998	IBTK	A015-C-104	Human	Colorectum	FAP	1.09e-20	-3.23e-01	-0.1899
25998	IBTK	A001-C-014	Human	Colorectum	FAP	1.65e-06	-1.50e-01	0.0135
25998	IBTK	A002-C-016	Human	Colorectum	FAP	1.96e-10	-2.51e-01	0.0521
25998	IBTK	A015-C-002	Human	Colorectum	FAP	5.44e-08	-2.85e-01	-0.0763
25998	IBTK	A001-C-203	Human	Colorectum	FAP	3.30e-04	-2.23e-01	-0.0481
25998	IBTK	A002-C-116	Human	Colorectum	FAP	4.54e-18	-2.21e-01	-0.0452

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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
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:0010563	Colorectum	AD	negative regulation of phosphorus metabolic process	130/3918	442/18723	1.26e-05	2.76e-04	130
GO:0045936	Colorectum	AD	negative regulation of phosphate metabolic process	129/3918	441/18723	1.81e-05	3.76e-04	129
GO:0051348	Colorectum	AD	negative regulation of transferase activity	85/3918	268/18723	2.07e-05	4.19e-04	85
GO:0042326	Colorectum	AD	negative regulation of phosphorylation	112/3918	385/18723	8.02e-05	1.27e-03	112
GO:0001933	Colorectum	AD	negative regulation of protein phosphorylation	101/3918	342/18723	9.39e-05	1.42e-03	101
GO:0006469	Colorectum	AD	negative regulation of protein kinase activity	65/3918	212/18723	5.21e-04	5.62e-03	65
GO:0033673	Colorectum	AD	negative regulation of kinase activity	71/3918	237/18723	6.18e-04	6.47e-03	71
GO:0051651	Colorectum	AD	maintenance of location in cell	61/3918	214/18723	5.02e-03	3.37e-02	61
GO:0061099	Colorectum	AD	negative regulation of protein tyrosine kinase activity	13/3918	31/18723	6.53e-03	4.06e-02	13
GO:00513482	Colorectum	MSS	negative regulation of transferase activity	80/3467	268/18723	4.06e-06	1.17e-04	80
GO:00105632	Colorectum	MSS	negative regulation of phosphorus metabolic process	118/3467	442/18723	1.18e-05	2.77e-04	118
GO:00459362	Colorectum	MSS	negative regulation of phosphate metabolic process	117/3467	441/18723	1.74e-05	3.84e-04	117
GO:00423262	Colorectum	MSS	negative regulation of phosphorylation	103/3467	385/18723	3.76e-05	7.17e-04	103
GO:00019332	Colorectum	MSS	negative regulation of protein phosphorylation	93/3467	342/18723	4.54e-05	8.35e-04	93
GO:00336732	Colorectum	MSS	negative regulation of kinase activity	66/3467	237/18723	2.63e-04	3.54e-03	66
GO:00064692	Colorectum	MSS	negative regulation of protein kinase activity	60/3467	212/18723	3.08e-04	4.02e-03	60
GO:00516512	Colorectum	MSS	maintenance of location in cell	57/3467	214/18723	2.07e-03	1.76e-02	57
GO:00610991	Colorectum	MSS	negative regulation of protein tyrosine kinase activity	12/3467	31/18723	6.80e-03	4.39e-02	12
GO:00513484	Colorectum	FAP	negative regulation of transferase activity	63/2622	268/18723	1.82e-05	4.57e-04	63
GO:00019334	Colorectum	FAP	negative regulation of protein phosphorylation	75/2622	342/18723	4.02e-05	8.53e-04	75

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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

IBTK

SNV

Missense_Mutation

novel

c.346G>T

p.Asp116Tyr

p.D116Y

Q9P2D0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IBTK

SNV

Missense_Mutation

rs757965458

c.865N>A

p.Val289Ile

p.V289I

Q9P2D0

protein_coding

tolerated(0.15)

possibly_damaging(0.906)

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

IBTK

SNV

Missense_Mutation

c.3443C>T

p.Ser1148Phe

p.S1148F

Q9P2D0

protein_coding

deleterious(0.05)

possibly_damaging(0.526)

TCGA-BH-A0H5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

IBTK

SNV

Missense_Mutation

c.3134N>T

p.Ser1045Phe

p.S1045F

Q9P2D0

protein_coding

deleterious(0)

possibly_damaging(0.556)

TCGA-C8-A275-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

IBTK

SNV

Missense_Mutation

c.1406N>C

p.Arg469Thr

p.R469T

Q9P2D0

protein_coding

tolerated(0.06)

benign(0.094)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

IBTK

SNV

Missense_Mutation

rs772636120

c.2201N>A

p.Ser734Asn

p.S734N

Q9P2D0

protein_coding

tolerated(0.14)

possibly_damaging(0.448)

TCGA-GM-A2DO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

IBTK

SNV

Missense_Mutation

novel

c.604N>C

p.Gly202Arg

p.G202R

Q9P2D0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-GM-A5PV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

IBTK

SNV

Missense_Mutation

rs376596320

c.467G>A

p.Gly156Asp

p.G156D

Q9P2D0

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IBTK

SNV

Missense_Mutation

c.106T>G

p.Phe36Val

p.F36V

Q9P2D0

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

IBTK

SNV

Missense_Mutation

c.113N>G

p.Ser38Cys

p.S38C

Q9P2D0

protein_coding

deleterious(0.02)

probably_damaging(0.949)

TCGA-EA-A50E-01

Cervix

cervical & endocervical cancer

Female

<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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