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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:DLK1-RPS11

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DLK1-RPS11
FusionPDB ID: 23195
FusionGDB2.0 ID: 23195
HgeneTgene
Gene symbol

DLK1

RPS11

Gene ID

8788

6205

Gene namedelta like non-canonical Notch ligand 1ribosomal protein S11
SynonymsDLK|DLK-1|Delta1|FA1|PREF1|Pref-1|ZOG|pG2S11
Cytomap

14q32.2

19q13.33

Type of geneprotein-codingprotein-coding
Descriptionprotein delta homolog 1delta-like 1 homologfetal antigen 1preadipocyte factor 1secredeltin40S ribosomal protein S11small ribosomal subunit protein uS17
Modification date2020032920200327
UniProtAcc

P80370

Main function of 5'-partner protein: FUNCTION: May have a role in neuroendocrine differentiation.
.
Ensembl transtripts involved in fusion geneENST idsENST00000331224, ENST00000341267, 
ENST00000556051, 
ENST00000270625, 
ENST00000596873, ENST00000594493, 
ENST00000599561, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 7 X 4=22414 X 51 X 16=11424
# samples 988
** MAII scorelog2(9/224*10)=-1.31550182572793
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(88/11424*10)=-3.69842055050444
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DLK1 [Title/Abstract] AND RPS11 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DLK1 [Title/Abstract] AND RPS11 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DLK1(101200728)-RPS11(50001254), # samples:1
DLK1(101201247)-RPS11(50000561), # samples:1
Anticipated loss of major functional domain due to fusion event.DLK1-RPS11 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
DLK1-RPS11 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
DLK1-RPS11 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
DLK1-RPS11 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
DLK1-RPS11 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
DLK1-RPS11 seems lost the major protein functional domain in Tgene 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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneDLK1

GO:0045746

negative regulation of Notch signaling pathway

25093684



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr14:101200728/chr19:50001254)
- 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.
FGviewer

check buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across DLK1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across RPS11 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000341267DLK1chr14101200728+ENST00000596873RPS11chr1950001254+171114572421150302
ENST00000331224DLK1chr14101200728+ENST00000596873RPS11chr1950001254+855601160723187

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000341267ENST00000596873DLK1chr14101200728+RPS11chr1950001254+0.0051688440.99483114
ENST00000331224ENST00000596873DLK1chr14101200728+RPS11chr1950001254+0.041801490.9581985

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for DLK1-RPS11

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DLK1chr14101200728RPS11chr1950001254601145INGCQNGGTCLQHTQSRSATRTCLYT

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Potential FusionNeoAntigen Information of DLK1-RPS11 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
DLK1-RPS11_101200728_50001254.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
DLK1-RPS11chr14101200728chr1950001254601HLA-B39:06QHTQSRSA0.99820.72781119
DLK1-RPS11chr14101200728chr1950001254601HLA-A74:03HTQSRSATR0.97650.57731221
DLK1-RPS11chr14101200728chr1950001254601HLA-A74:09HTQSRSATR0.97650.57731221
DLK1-RPS11chr14101200728chr1950001254601HLA-A74:11HTQSRSATR0.97650.57731221
DLK1-RPS11chr14101200728chr1950001254601HLA-B39:06QHTQSRSAT0.9540.71861120
DLK1-RPS11chr14101200728chr1950001254601HLA-A31:02HTQSRSATR0.87380.56141221
DLK1-RPS11chr14101200728chr1950001254601HLA-A31:01HTQSRSATR0.98090.51621221
DLK1-RPS11chr14101200728chr1950001254601HLA-B15:04LQHTQSRSA0.80710.87511019
DLK1-RPS11chr14101200728chr1950001254601HLA-A74:01HTQSRSATR0.97650.57731221

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Potential FusionNeoAntigen Information of DLK1-RPS11 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of DLK1-RPS11

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
2844GGTCLQHTQSRSATDLK1RPS11chr14101200728chr1950001254601

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DLK1-RPS11

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN2844GGTCLQHTQSRSAT-7.9962-8.1096
HLA-B14:023BVN2844GGTCLQHTQSRSAT-5.70842-6.74372
HLA-B52:013W392844GGTCLQHTQSRSAT-6.83737-6.95077
HLA-B52:013W392844GGTCLQHTQSRSAT-4.4836-5.5189
HLA-A11:014UQ22844GGTCLQHTQSRSAT-10.0067-10.1201
HLA-A11:014UQ22844GGTCLQHTQSRSAT-9.03915-10.0745
HLA-A24:025HGA2844GGTCLQHTQSRSAT-6.56204-6.67544
HLA-A24:025HGA2844GGTCLQHTQSRSAT-5.42271-6.45801
HLA-B44:053DX82844GGTCLQHTQSRSAT-7.85648-8.89178
HLA-B44:053DX82844GGTCLQHTQSRSAT-5.3978-5.5112
HLA-A02:016TDR2844GGTCLQHTQSRSAT-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of DLK1-RPS11

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
DLK1-RPS11chr14101200728chr19500012541019LQHTQSRSACACACCCAGTCGAGAAGCGCCACAAGA
DLK1-RPS11chr14101200728chr19500012541119QHTQSRSAACCCAGTCGAGAAGCGCCACAAGA
DLK1-RPS11chr14101200728chr19500012541120QHTQSRSATACCCAGTCGAGAAGCGCCACAAGAACA
DLK1-RPS11chr14101200728chr19500012541221HTQSRSATRCAGTCGAGAAGCGCCACAAGAACATGT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of DLK1-RPS11

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
ACCDLK1-RPS11chr14101200728ENST00000331224chr1950001254ENST00000596873TCGA-OR-A5LC-01A

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Potential target of CAR-T therapy development for DLK1-RPS11

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to DLK1-RPS11

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to DLK1-RPS11

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource