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: FUS

Gene summary for FUS

Gene summary.

Gene information	Species	Human
	Gene symbol	FUS
	Gene ID	2521
	Gene name	FUS RNA binding protein
	Gene Alias	ALS6
	Cytomap	16p11.2
	Gene Type	protein-coding
	GO ID	GO:0000018
	UniProtAcc	P35637

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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
2521	FUS	GSM4909277	Human	Breast	Precancer	7.33e-03	5.12e-01	0.0177
2521	FUS	GSM4909280	Human	Breast	Precancer	4.39e-04	4.47e-01	0.0305
2521	FUS	GSM4909282	Human	Breast	IDC	8.52e-04	3.74e-01	-0.0288
2521	FUS	GSM4909286	Human	Breast	IDC	4.59e-05	4.27e-02	0.1081
2521	FUS	GSM4909287	Human	Breast	IDC	4.44e-02	1.41e-01	0.2057
2521	FUS	GSM4909293	Human	Breast	IDC	6.11e-10	3.83e-01	0.1581
2521	FUS	GSM4909294	Human	Breast	IDC	6.01e-18	-5.20e-01	0.2022
2521	FUS	GSM4909296	Human	Breast	IDC	5.75e-10	-2.31e-01	0.1524
2521	FUS	GSM4909297	Human	Breast	IDC	3.47e-18	-1.84e-01	0.1517
2521	FUS	GSM4909298	Human	Breast	IDC	6.09e-24	5.56e-01	0.1551
2521	FUS	GSM4909302	Human	Breast	IDC	2.85e-02	1.54e-01	0.1545
2521	FUS	GSM4909306	Human	Breast	IDC	9.57e-05	3.71e-01	0.1564
2521	FUS	GSM4909311	Human	Breast	IDC	7.25e-43	-3.80e-01	0.1534
2521	FUS	GSM4909312	Human	Breast	IDC	5.27e-10	-1.98e-01	0.1552
2521	FUS	GSM4909313	Human	Breast	IDC	5.98e-03	4.96e-02	0.0391
2521	FUS	GSM4909315	Human	Breast	IDC	4.99e-03	-2.02e-01	0.21
2521	FUS	GSM4909316	Human	Breast	IDC	1.85e-06	-3.60e-01	0.21
2521	FUS	GSM4909317	Human	Breast	IDC	1.32e-08	4.40e-01	0.1355
2521	FUS	GSM4909319	Human	Breast	IDC	8.86e-51	-3.40e-01	0.1563
2521	FUS	GSM4909320	Human	Breast	IDC	8.93e-08	-2.79e-01	0.1575

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
Prostate		BPH: Benign Prostatic Hyperplasia
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:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00434849	Breast	Precancer	regulation of RNA splicing	34/1080	148/18723	2.66e-12	4.75e-10	34
GO:00100389	Breast	Precancer	response to metal ion	47/1080	373/18723	3.88e-07	1.79e-05	47
GO:19033118	Breast	Precancer	regulation of mRNA metabolic process	38/1080	288/18723	1.63e-06	5.97e-05	38
GO:00313309	Breast	Precancer	negative regulation of cellular catabolic process	34/1080	262/18723	8.16e-06	2.20e-04	34
GO:00064028	Breast	Precancer	mRNA catabolic process	31/1080	232/18723	1.12e-05	2.93e-04	31
GO:00064018	Breast	Precancer	RNA catabolic process	34/1080	278/18723	2.88e-05	6.39e-04	34
GO:19033129	Breast	Precancer	negative regulation of mRNA metabolic process	16/1080	92/18723	6.70e-05	1.35e-03	16
GO:00098959	Breast	Precancer	negative regulation of catabolic process	36/1080	320/18723	9.92e-05	1.83e-03	36
GO:00346558	Breast	Precancer	nucleobase-containing compound catabolic process	42/1080	407/18723	1.91e-04	3.06e-03	42
GO:00467007	Breast	Precancer	heterocycle catabolic process	44/1080	445/18723	3.49e-04	4.88e-03	44
GO:00712488	Breast	Precancer	cellular response to metal ion	24/1080	197/18723	4.35e-04	5.79e-03	24
GO:00442708	Breast	Precancer	cellular nitrogen compound catabolic process	44/1080	451/18723	4.64e-04	6.12e-03	44
GO:00712418	Breast	Precancer	cellular response to inorganic substance	26/1080	226/18723	6.23e-04	7.78e-03	26
GO:00194397	Breast	Precancer	aromatic compound catabolic process	44/1080	467/18723	9.55e-04	1.07e-02	44
GO:00510548	Breast	Precancer	positive regulation of DNA metabolic process	23/1080	201/18723	1.34e-03	1.41e-02	23
GO:19013617	Breast	Precancer	organic cyclic compound catabolic process	45/1080	495/18723	1.73e-03	1.74e-02	45
GO:00434888	Breast	Precancer	regulation of mRNA stability	19/1080	158/18723	1.92e-03	1.86e-02	19
GO:20010208	Breast	Precancer	regulation of response to DNA damage stimulus	24/1080	219/18723	1.93e-03	1.87e-02	24
GO:00515925	Breast	Precancer	response to calcium ion	18/1080	149/18723	2.37e-03	2.19e-02	18

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501416	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0502216	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa030408	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
hsa0501417	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0502217	Breast	Precancer	Pathways of neurodegeneration - multiple diseases	112/684	476/8465	6.96e-27	2.44e-25	1.87e-25	112
hsa0304013	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
hsa0501423	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0502223	Breast	IDC	Pathways of neurodegeneration - multiple diseases	116/867	476/8465	3.63e-20	1.18e-18	8.82e-19	116
hsa0304023	Breast	IDC	Spliceosome	40/867	217/8465	1.53e-04	1.42e-03	1.06e-03	40
hsa0501433	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0502233	Breast	IDC	Pathways of neurodegeneration - multiple diseases	116/867	476/8465	3.63e-20	1.18e-18	8.82e-19	116
hsa0304033	Breast	IDC	Spliceosome	40/867	217/8465	1.53e-04	1.42e-03	1.06e-03	40
hsa0501443	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0502243	Breast	DCIS	Pathways of neurodegeneration - multiple diseases	114/846	476/8465	4.74e-20	1.53e-18	1.13e-18	114
hsa0501453	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0502253	Breast	DCIS	Pathways of neurodegeneration - multiple diseases	114/846	476/8465	4.74e-20	1.53e-18	1.13e-18	114
hsa05014	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa05022	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa03040	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73
hsa03015	Colorectum	AD	mRNA surveillance pathway	35/2092	97/8465	7.95e-03	3.13e-02	2.00e-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

FUS

SNV

Missense_Mutation

c.1530N>C

p.Lys510Asn

p.K510N

P35637

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.601)

TCGA-A8-A08O-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

FUS

SNV

Missense_Mutation

c.259N>A

p.Ser87Thr

p.S87T

P35637

protein_coding

tolerated(0.23)

benign(0.133)

TCGA-E2-A1LS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cyclophosphamide

FUS

SNV

Missense_Mutation

novel

c.1327N>A

p.Glu443Lys

p.E443K

P35637

protein_coding

deleterious(0.01)

probably_damaging(0.996)

TCGA-UU-A93S-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

FUS

insertion

Nonsense_Mutation

novel

c.660_661insCGTCAGCCACAATGCCCTGAATGTTGCTTTTCTTAAACCTG

p.Ser221ArgfsTer12

p.S221Rfs*12

P35637

protein_coding

TCGA-AN-A0FK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

FUS

SNV

Missense_Mutation

c.1130G>A

p.Arg377Gln

p.R377Q

P35637

protein_coding

deleterious(0.01)

benign(0.158)

TCGA-A6-6781-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

oxaliplatin

FUS

SNV

Missense_Mutation

rs768259829

c.1249G>A

p.Gly417Ser

p.G417S

P35637

protein_coding

tolerated(0.2)

benign(0.113)

TCGA-A5-A0G9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

FUS

SNV

Missense_Mutation

rs121909671

c.1562N>A

p.Arg521His

p.R521H

P35637

protein_coding

deleterious_low_confidence(0.01)

benign(0)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

FUS

SNV

Missense_Mutation

novel

c.86G>A

p.Ser29Asn

p.S29N

P35637

protein_coding

tolerated(0.18)

benign(0.003)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

FUS

SNV

Missense_Mutation

c.1553G>T

p.Arg518Ile

p.R518I

P35637

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.986)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

FUS

SNV

Missense_Mutation

novel

c.158N>T

p.Ser53Ile

p.S53I

P35637

protein_coding

deleterious(0.01)

probably_damaging(0.914)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

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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
2521	FUS	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		ATRA	TRETINOIN	10691862

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