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: IRAK1

Gene summary for IRAK1

Gene summary.

Gene information	Species	Human
	Gene symbol	IRAK1
	Gene ID	3654
	Gene name	interleukin 1 receptor associated kinase 1
	Gene Alias	IRAK
	Cytomap	Xq28
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	P51617

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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
3654	IRAK1	HTA11_2487_2000001011	Human	Colorectum	SER	1.16e-05	3.08e-01	-0.1808
3654	IRAK1	HTA11_1938_2000001011	Human	Colorectum	AD	2.12e-07	3.56e-01	-0.0811
3654	IRAK1	HTA11_347_2000001011	Human	Colorectum	AD	7.12e-05	2.18e-01	-0.1954
3654	IRAK1	HTA11_3361_2000001011	Human	Colorectum	AD	1.22e-02	2.63e-01	-0.1207
3654	IRAK1	HTA11_696_2000001011	Human	Colorectum	AD	2.42e-04	2.70e-01	-0.1464
3654	IRAK1	HTA11_1391_2000001011	Human	Colorectum	AD	1.37e-13	4.88e-01	-0.059
3654	IRAK1	HTA11_546_2000001011	Human	Colorectum	AD	3.87e-03	3.32e-01	-0.0842
3654	IRAK1	HTA11_866_3004761011	Human	Colorectum	AD	2.93e-07	2.63e-01	0.096
3654	IRAK1	HTA11_10623_2000001011	Human	Colorectum	AD	5.58e-03	2.97e-01	-0.0177
3654	IRAK1	HTA11_6801_2000001011	Human	Colorectum	SER	4.08e-02	4.66e-01	0.0171
3654	IRAK1	HTA11_10711_2000001011	Human	Colorectum	AD	1.19e-02	2.29e-01	0.0338
3654	IRAK1	HTA11_7696_3000711011	Human	Colorectum	AD	1.88e-13	3.49e-01	0.0674
3654	IRAK1	HTA11_99999970781_79442	Human	Colorectum	MSS	7.67e-03	2.04e-01	0.294
3654	IRAK1	HTA11_99999965062_69753	Human	Colorectum	MSI-H	3.02e-03	4.29e-01	0.3487
3654	IRAK1	HTA11_99999971662_82457	Human	Colorectum	MSS	4.76e-28	6.89e-01	0.3859
3654	IRAK1	HTA11_99999973899_84307	Human	Colorectum	MSS	1.81e-07	4.96e-01	0.2585
3654	IRAK1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.07e-24	6.99e-01	0.3005
3654	IRAK1	LZE2T	Human	Esophagus	ESCC	2.17e-04	4.47e-01	0.082
3654	IRAK1	LZE4T	Human	Esophagus	ESCC	4.03e-03	4.77e-02	0.0811
3654	IRAK1	LZE5T	Human	Esophagus	ESCC	1.15e-02	1.66e-01	0.0514

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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:007135711	Liver	HCC	cellular response to type I interferon	38/7958	52/18723	7.59e-06	8.98e-05	38
GO:004312312	Liver	HCC	positive regulation of I-kappaB kinase/NF-kappaB signaling	108/7958	186/18723	1.28e-05	1.43e-04	108
GO:00324814	Liver	HCC	positive regulation of type I interferon production	41/7958	58/18723	1.29e-05	1.44e-04	41
GO:003109822	Liver	HCC	stress-activated protein kinase signaling cascade	138/7958	247/18723	1.43e-05	1.57e-04	138
GO:005140322	Liver	HCC	stress-activated MAPK cascade	134/7958	239/18723	1.50e-05	1.64e-04	134
GO:004312212	Liver	HCC	regulation of I-kappaB kinase/NF-kappaB signaling	138/7958	249/18723	2.47e-05	2.58e-04	138
GO:0032479	Liver	HCC	regulation of type I interferon production	60/7958	95/18723	3.84e-05	3.80e-04	60
GO:0032606	Liver	HCC	type I interferon production	60/7958	95/18723	3.84e-05	3.80e-04	60
GO:007190021	Liver	HCC	regulation of protein serine/threonine kinase activity	189/7958	359/18723	5.97e-05	5.47e-04	189
GO:000926611	Liver	HCC	response to temperature stimulus	101/7958	178/18723	8.55e-05	7.48e-04	101
GO:00467775	Liver	HCC	protein autophosphorylation	123/7958	227/18723	2.40e-04	1.80e-03	123
GO:007145311	Liver	HCC	cellular response to oxygen levels	98/7958	177/18723	3.63e-04	2.52e-03	98
GO:003629411	Liver	HCC	cellular response to decreased oxygen levels	90/7958	161/18723	4.03e-04	2.72e-03	90
GO:007145611	Liver	HCC	cellular response to hypoxia	84/7958	151/18723	7.57e-04	4.56e-03	84
GO:00705551	Liver	HCC	response to interleukin-1	80/7958	143/18723	7.95e-04	4.77e-03	80
GO:00510902	Liver	HCC	regulation of DNA-binding transcription factor activity	220/7958	440/18723	8.04e-04	4.82e-03	220
GO:004586021	Liver	HCC	positive regulation of protein kinase activity	194/7958	386/18723	1.16e-03	6.54e-03	194
GO:003249611	Liver	HCC	response to lipopolysaccharide	174/7958	343/18723	1.19e-03	6.62e-03	174
GO:00712166	Liver	HCC	cellular response to biotic stimulus	128/7958	246/18723	1.53e-03	8.10e-03	128
GO:003367411	Liver	HCC	positive regulation of kinase activity	230/7958	467/18723	1.72e-03	8.95e-03	230

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05171	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa05132	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa05135	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa04722	Colorectum	AD	Neurotrophin signaling pathway	50/2092	119/8465	2.28e-05	2.24e-04	1.43e-04	50
hsa05417	Colorectum	AD	Lipid and atherosclerosis	73/2092	215/8465	1.31e-03	8.27e-03	5.27e-03	73
hsa05170	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051711	Colorectum	AD	Coronavirus disease - COVID-19	113/2092	232/8465	9.90e-16	2.55e-14	1.63e-14	113
hsa051321	Colorectum	AD	Salmonella infection	102/2092	249/8465	7.65e-09	1.28e-07	8.17e-08	102
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051351	Colorectum	AD	Yersinia infection	58/2092	137/8465	3.90e-06	4.35e-05	2.78e-05	58
hsa047221	Colorectum	AD	Neurotrophin signaling pathway	50/2092	119/8465	2.28e-05	2.24e-04	1.43e-04	50
hsa054171	Colorectum	AD	Lipid and atherosclerosis	73/2092	215/8465	1.31e-03	8.27e-03	5.27e-03	73
hsa051701	Colorectum	AD	Human immunodeficiency virus 1 infection	72/2092	212/8465	1.40e-03	8.46e-03	5.39e-03	72
hsa051712	Colorectum	SER	Coronavirus disease - COVID-19	98/1580	232/8465	3.33e-17	8.50e-16	6.17e-16	98
hsa051322	Colorectum	SER	Salmonella infection	77/1580	249/8465	1.56e-06	2.35e-05	1.71e-05	77
hsa051302	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60
hsa051352	Colorectum	SER	Yersinia infection	43/1580	137/8465	2.15e-04	2.10e-03	1.52e-03	43
hsa051702	Colorectum	SER	Human immunodeficiency virus 1 infection	58/1580	212/8465	1.08e-03	8.56e-03	6.21e-03	58
hsa047222	Colorectum	SER	Neurotrophin signaling pathway	35/1580	119/8465	2.80e-03	2.02e-02	1.47e-02	35

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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

IRAK1

SNV

Missense_Mutation

c.1748A>G

p.Asn583Ser

p.N583S

P51617

protein_coding

tolerated(0.07)

probably_damaging(0.996)

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

IRAK1

SNV

Missense_Mutation

c.1263N>C

p.Gln421His

p.Q421H

P51617

protein_coding

deleterious(0.02)

probably_damaging(0.925)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

IRAK1

SNV

Missense_Mutation

rs782334259

c.1984N>G

p.Ile662Val

p.I662V

P51617

protein_coding

tolerated(0.1)

probably_damaging(0.984)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

IRAK1

insertion

In_Frame_Ins

novel

c.464_465insCCCCTCTGTGAGATTTCCCGGGGC

p.Pro156_Glu157insSerValArgPheProGlyAlaPro

p.P156_E157insSVRFPGAP

P51617

protein_coding

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

IRAK1

SNV

Missense_Mutation

novel

c.335N>A

p.Gly112Asp

p.G112D

P51617

protein_coding

tolerated(0.16)

benign(0.006)

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

IRAK1

SNV

Missense_Mutation

novel

c.1555N>C

p.Glu519Gln

p.E519Q

P51617

protein_coding

tolerated(0.15)

probably_damaging(0.998)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

IRAK1

insertion

Nonsense_Mutation

novel

c.333_334insTAAA

p.Gly112Ter

p.G112*

P51617

protein_coding

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

IRAK1

SNV

Missense_Mutation

novel

c.505N>G

p.Pro169Ala

p.P169A

P51617

protein_coding

deleterious(0.01)

benign(0.165)

TCGA-A6-2683-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

irinotecan

IRAK1

SNV

Missense_Mutation

c.1936N>A

p.Ala646Thr

p.A646T

P51617

protein_coding

tolerated(0.6)

benign(0.015)

TCGA-AA-3663-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

IRAK1

SNV

Missense_Mutation

c.1141A>T

p.Thr381Ser

p.T381S

P51617

protein_coding

deleterious(0.01)

possibly_damaging(0.874)

TCGA-CK-4947-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Other, specify in notes

folinic

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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
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR		PF-562271	PF-00562271
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR	inhibitor	249565765
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR		GEFITINIB	GEFITINIB
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR		GW441756X	GW441756X
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR		LINIFANIB	LINIFANIB
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR	inhibitor	249565764
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR	inhibitor	385612233
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR		TAMATINIB	R-406
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR		RG-1530	RG-1530
3654	IRAK1	DRUGGABLE GENOME, KINASE, SERINE THREONINE KINASE, ENZYME, TRANSCRIPTION FACTOR	inhibitor	348353615

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