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: TLR6

Gene summary for TLR6

Gene summary.

Gene information	Species	Human
	Gene symbol	TLR6
	Gene ID	10333
	Gene name	toll like receptor 6
	Gene Alias	CD286
	Cytomap	4p14
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	B2R933

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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
10333	TLR6	HCC2	Human	Liver	HCC	2.61e-17	1.85e+00	0.5341
10333	TLR6	HCC5	Human	Liver	HCC	9.14e-06	1.41e+00	0.4932

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:000697922	Liver	HCC	response to oxidative stress	281/7958	446/18723	9.75e-19	1.24e-16	281
GO:004325422	Liver	HCC	regulation of protein-containing complex assembly	264/7958	428/18723	5.47e-16	4.39e-14	264
GO:006219722	Liver	HCC	cellular response to chemical stress	216/7958	337/18723	6.86e-16	5.44e-14	216
GO:003459922	Liver	HCC	cellular response to oxidative stress	183/7958	288/18723	3.65e-13	1.93e-11	183
GO:003133412	Liver	HCC	positive regulation of protein-containing complex assembly	150/7958	237/18723	7.35e-11	2.63e-09	150
GO:190165321	Liver	HCC	cellular response to peptide	211/7958	359/18723	2.86e-10	9.63e-09	211
GO:00022211	Liver	HCC	pattern recognition receptor signaling pathway	107/7958	172/18723	1.37e-07	2.58e-06	107
GO:007099722	Liver	HCC	neuron death	202/7958	361/18723	1.44e-07	2.70e-06	202
GO:190121412	Liver	HCC	regulation of neuron death	179/7958	319/18723	5.65e-07	9.01e-06	179
GO:000724912	Liver	HCC	I-kappaB kinase/NF-kappaB signaling	156/7958	281/18723	6.66e-06	8.00e-05	156
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:190121612	Liver	HCC	positive regulation of neuron death	62/7958	97/18723	1.67e-05	1.81e-04	62
GO:004312212	Liver	HCC	regulation of I-kappaB kinase/NF-kappaB signaling	138/7958	249/18723	2.47e-05	2.58e-04	138
GO:200037722	Liver	HCC	regulation of reactive oxygen species metabolic process	92/7958	157/18723	3.34e-05	3.35e-04	92
GO:007190021	Liver	HCC	regulation of protein serine/threonine kinase activity	189/7958	359/18723	5.97e-05	5.47e-04	189
GO:200105722	Liver	HCC	reactive nitrogen species metabolic process	51/7958	82/18723	2.50e-04	1.86e-03	51
GO:004620922	Liver	HCC	nitric oxide metabolic process	50/7958	81/18723	3.72e-04	2.56e-03	50
GO:008016422	Liver	HCC	regulation of nitric oxide metabolic process	41/7958	64/18723	4.06e-04	2.74e-03	41
GO:200037912	Liver	HCC	positive regulation of reactive oxygen species metabolic process	47/7958	76/18723	5.19e-04	3.38e-03	47
GO:00510902	Liver	HCC	regulation of DNA-binding transcription factor activity	220/7958	440/18723	8.04e-04	4.82e-03	220

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513242	Liver	HCC	Salmonella infection	178/4020	249/8465	5.90e-15	1.98e-13	1.10e-13	178
hsa0414521	Liver	HCC	Phagosome	93/4020	152/8465	4.27e-04	1.88e-03	1.05e-03	93
hsa0541742	Liver	HCC	Lipid and atherosclerosis	118/4020	215/8465	1.66e-02	3.92e-02	2.18e-02	118
hsa0513252	Liver	HCC	Salmonella infection	178/4020	249/8465	5.90e-15	1.98e-13	1.10e-13	178
hsa0414531	Liver	HCC	Phagosome	93/4020	152/8465	4.27e-04	1.88e-03	1.05e-03	93
hsa0541752	Liver	HCC	Lipid and atherosclerosis	118/4020	215/8465	1.66e-02	3.92e-02	2.18e-02	118

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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

TLR6

SNV

Missense_Mutation

novel

c.2030N>T

p.Asn677Ile

p.N677I

Q9Y2C9

protein_coding

deleterious(0)

probably_damaging(0.949)

TCGA-AC-A8OR-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TLR6

SNV

Missense_Mutation

rs374402826

c.2143N>A

p.Glu715Lys

p.E715K

Q9Y2C9

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TLR6

insertion

Nonsense_Mutation

novel

c.2140_2141insGTAAAGGGATATATGGACTTAATCATAAGCTGTTGAGGTGAAAG

p.Tyr714CysfsTer14

p.Y714Cfs*14

Q9Y2C9

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TLR6

insertion

Nonsense_Mutation

novel

c.234_235insTGAATGCTCAAGTCCCTTATGTAAAATGGCATACTTCCAAC

p.Thr79Ter

p.T79*

Q9Y2C9

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

TLR6

insertion

In_Frame_Ins

novel

c.1824_1825insGGTGAGGTT

p.Tyr608_Leu609insGlyGluVal

p.Y608_L609insGEV

Q9Y2C9

protein_coding

TCGA-AN-A049-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TLR6

insertion

Nonsense_Mutation

novel

c.932_933insGTATCAAGTGAAGTGTTAGAGGGCTGGCCTGATTCTTATAAGTGTG

p.His311GlnfsTer7

p.H311Qfs*7

Q9Y2C9

protein_coding

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

TLR6

SNV

Missense_Mutation

novel

c.656C>T

p.Thr219Ile

p.T219I

Q9Y2C9

protein_coding

deleterious(0.03)

benign(0.127)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TLR6

SNV

Missense_Mutation

rs374402826

c.2143G>A

p.Glu715Lys

p.E715K

Q9Y2C9

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A6-6141-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

5-fu

TLR6

SNV

Missense_Mutation

novel

c.2025N>T

p.Glu675Asp

p.E675D

Q9Y2C9

protein_coding

deleterious(0)

possibly_damaging(0.693)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

TLR6

SNV

Missense_Mutation

c.784N>G

p.Thr262Ala

p.T262A

Q9Y2C9

protein_coding

tolerated(0.54)

benign(0.031)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

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
10333	TLR6	DRUGGABLE GENOME		MALP-2S

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