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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
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Fusion gene:RBFOX2-LGALS2 (FusionGDB2 ID:72676)

Fusion Gene Summary for RBFOX2-LGALS2

Fusion gene summary

Fusion gene information	Fusion gene name: RBFOX2-LGALS2
	Fusion gene ID: 72676
		Hgene	Tgene
	Gene symbol	RBFOX2	LGALS2
	Gene ID	23543	3958
	Gene name	RNA binding fox-1 homolog 2	galectin 3
	Synonyms	FOX2\|Fox-2\|HNRBP2\|HRNBP2\|RBM9\|RTA\|dJ106I20.3\|fxh	CBP35\|GAL3\|GALBP\|GALIG\|L31\|LGALS2\|MAC2
	Cytomap	22q12.3	14q22.3
	Type of gene	protein-coding	protein-coding
	Description	RNA binding protein fox-1 homolog 2RNA binding protein, fox-1 homolog 2RNA-binding motif protein 9fox-1 homolog Bfox-1 homologuehexaribonucleotide-binding protein 2repressor of tamoxifen transcriptional activity	galectin-335 kDa lectinIgE-binding proteinMAC-2 antigenadvanced glycation end-product receptor 3carbohydrate-binding protein 35epididymis secretory sperm binding proteingalactose-specific lectin 3laminin-binding proteinlectin L-29lectin, galacto
	Modification date	20200327	20200322
	UniProtAcc	.	P05162
	Ensembl transtripts involved in fusion gene	ENST00000438146, ENST00000262829, ENST00000359369, ENST00000397303, ENST00000405409, ENST00000414461, ENST00000416721, ENST00000449924,	ENST00000215886,
Fusion gene scores	* DoF score	39 X 29 X 13=14703	4 X 2 X 4=32
	# samples	48	6
	** MAII score	log2(48/14703*10)=-4.93693233652239 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(6/32*10)=0.906890595608518 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0
Context	PubMed: RBFOX2 [Title/Abstract] AND LGALS2 [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint	RBFOX2(36424288)-LGALS2(37967938), # samples:3
Anticipated loss of major functional domain due to fusion event.	RBFOX2-LGALS2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.

* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	RBFOX2	GO:0030520	intracellular estrogen receptor signaling pathway	11875103
Hgene	RBFOX2	GO:0045892	negative regulation of transcription, DNA-templated	11875103
Tgene	LGALS2	GO:0002548	monocyte chemotaxis	10925302
Tgene	LGALS2	GO:0030593	neutrophil chemotaxis	10925302
Tgene	LGALS2	GO:0031334	positive regulation of protein complex assembly	24846175
Tgene	LGALS2	GO:0045806	negative regulation of endocytosis	19706535
Tgene	LGALS2	GO:0048245	eosinophil chemotaxis	10925302
Tgene	LGALS2	GO:0048246	macrophage chemotaxis	10925302
Tgene	LGALS2	GO:0050918	positive chemotaxis	10925302
Tgene	LGALS2	GO:0070232	regulation of T cell apoptotic process	8692888
Tgene	LGALS2	GO:0071674	mononuclear cell migration	10925302
Tgene	LGALS2	GO:0071677	positive regulation of mononuclear cell migration	10925302
Tgene	LGALS2	GO:0090280	positive regulation of calcium ion import	10925302
Tgene	LGALS2	GO:1903078	positive regulation of protein localization to plasma membrane	24846175
Tgene	LGALS2	GO:2001200	positive regulation of dendritic cell differentiation	16116184
Tgene	LGALS2	GO:2001237	negative regulation of extrinsic apoptotic signaling pathway	22761016

Fusion gene breakpoints across RBFOX2 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across LGALS2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.

Source	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	GBM	TCGA-19-2625-01A	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
ChimerDB4	GBM	TCGA-19-2625-01A	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
ChimerDB4	GBM	TCGA-19-2625-01A	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
ChimerDB4	GBM	TCGA-19-2625	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-

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Fusion Gene ORF analysis for RBFOX2-LGALS2

Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
Frame-shift	ENST00000438146	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
In-frame	ENST00000438146	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
In-frame	ENST00000438146	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000262829	ENST00000215886	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000262829	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
intron-3CDS	ENST00000262829	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000262829	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000359369	ENST00000215886	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000359369	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
intron-3CDS	ENST00000359369	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000359369	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000397303	ENST00000215886	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000397303	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
intron-3CDS	ENST00000397303	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000397303	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000405409	ENST00000215886	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000405409	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
intron-3CDS	ENST00000405409	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000405409	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000414461	ENST00000215886	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000414461	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
intron-3CDS	ENST00000414461	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000414461	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000416721	ENST00000215886	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000416721	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
intron-3CDS	ENST00000416721	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000416721	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000438146	ENST00000215886	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000449924	ENST00000215886	RBFOX2	chr22	36423100	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000449924	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37966742	-
intron-3CDS	ENST00000449924	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-
intron-3CDS	ENST00000449924	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	Seq length (transcript)	BP loci (transcript)	Predicted start (transcript)	Predicted stop (transcript)	Seq length (amino acids)
ENST00000438146	RBFOX2	chr22	36424288	-	ENST00000215886	LGALS2	chr22	37967938	-	594	186	0	578	192
ENST00000438146	RBFOX2	chr22	36424287	-	ENST00000215886	LGALS2	chr22	37967938	-	594	186	0	578	192

DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.

Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand	No-coding score	Coding score
ENST00000438146	ENST00000215886	RBFOX2	chr22	36424288	-	LGALS2	chr22	37967938	-	0.002727364	0.9972727
ENST00000438146	ENST00000215886	RBFOX2	chr22	36424287	-	LGALS2	chr22	37967938	-	0.002727364	0.9972727

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Fusion Genomic Features for RBFOX2-LGALS2

FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for RBFOX2-LGALS2

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr22:36424288/chr22:37967938)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
.	LGALS2 P05162
FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.	FUNCTION: This protein binds beta-galactoside. Its physiological function is not yet known.

Retention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page

* Minus value of BPloci means that the break pointn is located before the CDS.

- In-frame and retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Tgene

LGALS2

chr22:36424287

chr22:37967938

ENST00000215886

4_131

133.0

Domain

Galectin

Tgene

LGALS2

chr22:36424288

chr22:37967938

ENST00000215886

4_131

133.0

Domain

Galectin

Tgene

LGALS2

chr22:36424287

chr22:37967938

ENST00000215886

65_71

133.0

Region

Beta-galactoside binding

Tgene

LGALS2

chr22:36424288

chr22:37967938

ENST00000215886

65_71

133.0

Region

Beta-galactoside binding

- In-frame and not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000262829

273_377

359.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000405409

273_377

368.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000414461

273_377

371.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000416721

273_377

377.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000438146

273_377

452.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000449924

273_377

381.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000262829

273_377

359.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000405409

273_377

368.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000414461

273_377

371.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000416721

273_377

377.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000438146

273_377

452.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000449924

273_377

381.0

Compositional bias

Note=Ala-rich

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000262829

121_197

359.0

Domain

RRM

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000405409

121_197

368.0

Domain

RRM

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000414461

121_197

371.0

Domain

RRM

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000416721

121_197

377.0

Domain

RRM

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000438146

121_197

452.0

Domain

RRM

Hgene

RBFOX2

chr22:36424287

chr22:37967938

ENST00000449924

121_197

381.0

Domain

RRM

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000262829

121_197

359.0

Domain

RRM

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000405409

121_197

368.0

Domain

RRM

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000414461

121_197

371.0

Domain

RRM

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000416721

121_197

377.0

Domain

RRM

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000438146

121_197

452.0

Domain

RRM

Hgene

RBFOX2

chr22:36424288

chr22:37967938

ENST00000449924

121_197

381.0

Domain

RRM

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Fusion Gene Sequence for RBFOX2-LGALS2

For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>72676_72676_1_RBFOX2-LGALS2_RBFOX2_chr22_36424287_ENST00000438146_LGALS2_chr22_37967938_ENST00000215886_length(transcript)=594nt_BP=186nt
ATGGCGGAGGGCGCCCAGCCGCATCAGCCGCCTCAGCTCGGGCCCGGCGCCGCCGCCCGGGGCATGAAGCGGGAGTCGGAGCTGGAGCTG
CCGGTGCCCGGAGCGGGAGGAGACGGAGCCGATCCCGGCCTGAGCAAGCGGCCGCGCACTGAGGAGGCGGCGGCCGACGGTGGCGGCGGG
ATGCAGGGGGAACTTGAGGTTAAGAACATGGACATGAAGCCGGGGTCAACCCTGAAGATCACAGGCAGCATCGCCGATGGCACTGATGGC
TTTGTAATTAATCTGGGCCAGGGGACAGACAAGCTGAACCTGCATTTCAACCCTCGCTTCAGCGAATCCACCATTGTCTGCAACTCATTG
GACGGCAGCAACTGGGGGCAAGAACAACGGGAAGATCACCTGTGCTTCAGCCCAGGGTCAGAGGTCAAGTTCACAGTGACCTTTGAGAGT
GACAAATTCAAGGTGAAGCTGCCAGATGGGCACGAGCTGACTTTTCCCAACAGGCTGGGTCACAGCCACCTGAGCTACCTGAGCGTAAGG

>72676_72676_1_RBFOX2-LGALS2_RBFOX2_chr22_36424287_ENST00000438146_LGALS2_chr22_37967938_ENST00000215886_length(amino acids)=192AA_BP=56
MAEGAQPHQPPQLGPGAAARGMKRESELELPVPGAGGDGADPGLSKRPRTEEAAADGGGGMQGELEVKNMDMKPGSTLKITGSIADGTDG
FVINLGQGTDKLNLHFNPRFSESTIVCNSLDGSNWGQEQREDHLCFSPGSEVKFTVTFESDKFKVKLPDGHELTFPNRLGHSHLSYLSVR

--------------------------------------------------------------
>72676_72676_2_RBFOX2-LGALS2_RBFOX2_chr22_36424288_ENST00000438146_LGALS2_chr22_37967938_ENST00000215886_length(transcript)=594nt_BP=186nt
ATGGCGGAGGGCGCCCAGCCGCATCAGCCGCCTCAGCTCGGGCCCGGCGCCGCCGCCCGGGGCATGAAGCGGGAGTCGGAGCTGGAGCTG
CCGGTGCCCGGAGCGGGAGGAGACGGAGCCGATCCCGGCCTGAGCAAGCGGCCGCGCACTGAGGAGGCGGCGGCCGACGGTGGCGGCGGG
ATGCAGGGGGAACTTGAGGTTAAGAACATGGACATGAAGCCGGGGTCAACCCTGAAGATCACAGGCAGCATCGCCGATGGCACTGATGGC
TTTGTAATTAATCTGGGCCAGGGGACAGACAAGCTGAACCTGCATTTCAACCCTCGCTTCAGCGAATCCACCATTGTCTGCAACTCATTG
GACGGCAGCAACTGGGGGCAAGAACAACGGGAAGATCACCTGTGCTTCAGCCCAGGGTCAGAGGTCAAGTTCACAGTGACCTTTGAGAGT
GACAAATTCAAGGTGAAGCTGCCAGATGGGCACGAGCTGACTTTTCCCAACAGGCTGGGTCACAGCCACCTGAGCTACCTGAGCGTAAGG

>72676_72676_2_RBFOX2-LGALS2_RBFOX2_chr22_36424288_ENST00000438146_LGALS2_chr22_37967938_ENST00000215886_length(amino acids)=192AA_BP=56
MAEGAQPHQPPQLGPGAAARGMKRESELELPVPGAGGDGADPGLSKRPRTEEAAADGGGGMQGELEVKNMDMKPGSTLKITGSIADGTDG
FVINLGQGTDKLNLHFNPRFSESTIVCNSLDGSNWGQEQREDHLCFSPGSEVKFTVTFESDKFKVKLPDGHELTFPNRLGHSHLSYLSVR

--------------------------------------------------------------

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Fusion Gene PPI Analysis for RBFOX2-LGALS2

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs for RBFOX2-LGALS2

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for RBFOX2-LGALS2

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source