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:0001933111	Esophagus	ESCC	negative regulation of protein phosphorylation	213/8552	342/18723	3.54e-10	9.76e-09	213
GO:003367319	Esophagus	ESCC	negative regulation of kinase activity	154/8552	237/18723	1.38e-09	3.27e-08	154
GO:000646920	Esophagus	ESCC	negative regulation of protein kinase activity	140/8552	212/18723	1.53e-09	3.56e-08	140
GO:0051235110	Esophagus	ESCC	maintenance of location	200/8552	327/18723	1.01e-08	2.02e-07	200
GO:00507322	Esophagus	ESCC	negative regulation of peptidyl-tyrosine phosphorylation	42/8552	59/18723	6.35e-05	4.84e-04	42
GO:0051651111	Esophagus	ESCC	maintenance of location in cell	126/8552	214/18723	6.57e-05	5.00e-04	126
GO:00610997	Esophagus	ESCC	negative regulation of protein tyrosine kinase activity	25/8552	31/18723	7.13e-05	5.38e-04	25
GO:00182124	Esophagus	ESCC	peptidyl-tyrosine modification	202/8552	378/18723	1.34e-03	6.39e-03	202
GO:00181084	Esophagus	ESCC	peptidyl-tyrosine phosphorylation	200/8552	375/18723	1.60e-03	7.45e-03	200
GO:00507303	Esophagus	ESCC	regulation of peptidyl-tyrosine phosphorylation	144/8552	264/18723	2.22e-03	9.78e-03	144
GO:00610972	Esophagus	ESCC	regulation of protein tyrosine kinase activity	55/8552	90/18723	2.27e-03	9.99e-03	55
GO:00423267	Liver	NAFLD	negative regulation of phosphorylation	67/1882	385/18723	5.49e-06	1.98e-04	67
GO:00459367	Liver	NAFLD	negative regulation of phosphate metabolic process	73/1882	441/18723	1.31e-05	3.93e-04	73
GO:00105637	Liver	NAFLD	negative regulation of phosphorus metabolic process	73/1882	442/18723	1.42e-05	4.17e-04	73
GO:00513487	Liver	NAFLD	negative regulation of transferase activity	49/1882	268/18723	2.61e-05	7.03e-04	49
GO:00336736	Liver	NAFLD	negative regulation of kinase activity	40/1882	237/18723	7.49e-04	9.50e-03	40
GO:00019337	Liver	NAFLD	negative regulation of protein phosphorylation	52/1882	342/18723	1.63e-03	1.74e-02	52
GO:00512356	Liver	NAFLD	maintenance of location	50/1882	327/18723	1.75e-03	1.82e-02	50
GO:004593612	Liver	Cirrhotic	negative regulation of phosphate metabolic process	154/4634	441/18723	8.78e-07	1.83e-05	154
GO:001056312	Liver	Cirrhotic	negative regulation of phosphorus metabolic process	154/4634	442/18723	1.02e-06	2.11e-05	154

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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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