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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:NEO1-DPP8

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NEO1-DPP8
FusionPDB ID: 58613
FusionGDB2.0 ID: 58613
HgeneTgene
Gene symbol

NEO1

DPP8

Gene ID

4756

54878

Gene nameneogenin 1dipeptidyl peptidase 8
SynonymsIGDCC2|NGN|NTN1R2DP8|DPRP-1|DPRP1|MST097|MSTP097|MSTP135|MSTP141
Cytomap

15q24.1

15q22.31

Type of geneprotein-codingprotein-coding
Descriptionneogeninimmunoglobulin superfamily DCC subclass member 2neogenin homolog 1dipeptidyl peptidase 8DPP VIIIdipeptidyl peptidase IV-related protein 1dipeptidyl peptidase VIIIprolyl dipeptidase DPP8
Modification date2020031320200313
UniProtAcc

Q92859

Main function of 5'-partner protein: FUNCTION: Multi-functional cell surface receptor regulating cell adhesion in many diverse developmental processes, including neural tube and mammary gland formation, myogenesis and angiogenesis. Receptor for members of the BMP, netrin, and repulsive guidance molecule (RGM) families. Netrin-Neogenin interactions result in a chemoattractive axon guidance response and cell-cell adhesion, the interaction between NEO1/Neogenin and RGMa and RGMb induces a chemorepulsive response. {ECO:0000269|PubMed:21149453}.

Q6V1X1

Main function of 5'-partner protein: FUNCTION: Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. {ECO:0000269|PubMed:11012666, ECO:0000269|PubMed:12534281, ECO:0000269|PubMed:12662155, ECO:0000269|PubMed:15039077, ECO:0000269|PubMed:15664838, ECO:0000269|PubMed:20536396, ECO:0000305|PubMed:29382749}.
Ensembl transtripts involved in fusion geneENST idsENST00000261908, ENST00000339362, 
ENST00000558964, ENST00000560262, 
ENST00000560352, 
ENST00000339244, 
ENST00000559233, ENST00000560048, 
ENST00000300141, ENST00000321118, 
ENST00000321147, ENST00000341861, 
ENST00000358939, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 7 X 7=6865 X 6 X 4=120
# samples 156
** MAII scorelog2(15/686*10)=-2.19324607567693
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/120*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NEO1 [Title/Abstract] AND DPP8 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NEO1 [Title/Abstract] AND DPP8 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NEO1(73345146)-DPP8(65766626), # samples:2
Anticipated loss of major functional domain due to fusion event.NEO1-DPP8 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.
NEO1-DPP8 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.
* 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


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/chr15:73345146/chr15:65766626)
- 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 NEO1 (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 DPP8 (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)
ENST00000339362NEO1chr1573345146+ENST00000341861DPP8chr1565766626-61915772671769500
ENST00000339362NEO1chr1573345146+ENST00000358939DPP8chr1565766626-17375772671469400
ENST00000339362NEO1chr1573345146+ENST00000300141DPP8chr1565766626-20355772671769500
ENST00000339362NEO1chr1573345146+ENST00000321147DPP8chr1565766626-18805772671616449
ENST00000339362NEO1chr1573345146+ENST00000321118DPP8chr1565766626-18705772671622451
ENST00000261908NEO1chr1573345146+ENST00000341861DPP8chr1565766626-5936322121514500
ENST00000261908NEO1chr1573345146+ENST00000358939DPP8chr1565766626-1482322121214400
ENST00000261908NEO1chr1573345146+ENST00000300141DPP8chr1565766626-1780322121514500
ENST00000261908NEO1chr1573345146+ENST00000321147DPP8chr1565766626-1625322121361449
ENST00000261908NEO1chr1573345146+ENST00000321118DPP8chr1565766626-1615322121367451
ENST00000558964NEO1chr1573345146+ENST00000341861DPP8chr1565766626-5810196301388452
ENST00000558964NEO1chr1573345146+ENST00000358939DPP8chr1565766626-1356196301088352
ENST00000558964NEO1chr1573345146+ENST00000300141DPP8chr1565766626-1654196301388452
ENST00000558964NEO1chr1573345146+ENST00000321147DPP8chr1565766626-1499196301235401
ENST00000558964NEO1chr1573345146+ENST00000321118DPP8chr1565766626-1489196301241403
ENST00000560262NEO1chr1573345146+ENST00000341861DPP8chr1565766626-5810196301388452
ENST00000560262NEO1chr1573345146+ENST00000358939DPP8chr1565766626-1356196301088352
ENST00000560262NEO1chr1573345146+ENST00000300141DPP8chr1565766626-1654196301388452
ENST00000560262NEO1chr1573345146+ENST00000321147DPP8chr1565766626-1499196301235401
ENST00000560262NEO1chr1573345146+ENST00000321118DPP8chr1565766626-1489196301241403

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
ENST00000339362ENST00000341861NEO1chr1573345146+DPP8chr1565766626-3.77E-050.99996233
ENST00000339362ENST00000358939NEO1chr1573345146+DPP8chr1565766626-0.0005758480.9994242
ENST00000339362ENST00000300141NEO1chr1573345146+DPP8chr1565766626-0.0002069520.9997931
ENST00000339362ENST00000321147NEO1chr1573345146+DPP8chr1565766626-0.0003100580.99968994
ENST00000339362ENST00000321118NEO1chr1573345146+DPP8chr1565766626-0.0005674190.9994325
ENST00000261908ENST00000341861NEO1chr1573345146+DPP8chr1565766626-3.52E-050.99996483
ENST00000261908ENST00000358939NEO1chr1573345146+DPP8chr1565766626-0.0004902740.9995097
ENST00000261908ENST00000300141NEO1chr1573345146+DPP8chr1565766626-0.0001718130.9998281
ENST00000261908ENST00000321147NEO1chr1573345146+DPP8chr1565766626-0.0002479290.9997521
ENST00000261908ENST00000321118NEO1chr1573345146+DPP8chr1565766626-0.0004770810.9995229
ENST00000558964ENST00000341861NEO1chr1573345146+DPP8chr1565766626-3.33E-050.99996674
ENST00000558964ENST00000358939NEO1chr1573345146+DPP8chr1565766626-0.0003594890.99964046
ENST00000558964ENST00000300141NEO1chr1573345146+DPP8chr1565766626-0.0001509650.99984896
ENST00000558964ENST00000321147NEO1chr1573345146+DPP8chr1565766626-0.0001879620.99981207
ENST00000558964ENST00000321118NEO1chr1573345146+DPP8chr1565766626-0.0003351340.9996649
ENST00000560262ENST00000341861NEO1chr1573345146+DPP8chr1565766626-3.33E-050.99996674
ENST00000560262ENST00000358939NEO1chr1573345146+DPP8chr1565766626-0.0003594890.99964046
ENST00000560262ENST00000300141NEO1chr1573345146+DPP8chr1565766626-0.0001509650.99984896
ENST00000560262ENST00000321147NEO1chr1573345146+DPP8chr1565766626-0.0001879620.99981207
ENST00000560262ENST00000321118NEO1chr1573345146+DPP8chr1565766626-0.0003351340.9996649

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 NEO1-DPP8

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NEO1chr1573345146DPP8chr156576662619653PGAAAARSGSAPQSPGDFKCPIKEEI
NEO1chr1573345146DPP8chr1565766626322101PGAAAARSGSAPQSPGDFKCPIKEEI
NEO1chr1573345146DPP8chr1565766626577101PGAAAARSGSAPQSPGDFKCPIKEEI

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Potential FusionNeoAntigen Information of NEO1-DPP8 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.
NEO1-DPP8_73345146_65766626.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)
NEO1-DPP8chr1573345146chr1565766626322HLA-C01:17SAPQSPGDF0.27070.9319918
NEO1-DPP8chr1573345146chr1565766626322HLA-C01:30SAPQSPGDF0.18570.9484918
NEO1-DPP8chr1573345146chr1565766626322HLA-C01:02SAPQSPGDF0.31180.9289918
NEO1-DPP8chr1573345146chr1565766626322HLA-C01:03SAPQSPGDF0.14980.8894918

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Potential FusionNeoAntigen Information of NEO1-DPP8 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 NEO1-DPP8

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
8221RSGSAPQSPGDFKCNEO1DPP8chr1573345146chr1565766626322

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NEO1-DPP8

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-B14:023BVN8221RSGSAPQSPGDFKC-7.15543-7.26883
HLA-B14:023BVN8221RSGSAPQSPGDFKC-4.77435-5.80965
HLA-B52:013W398221RSGSAPQSPGDFKC-6.80875-6.92215
HLA-B52:013W398221RSGSAPQSPGDFKC-4.20386-5.23916
HLA-A11:014UQ28221RSGSAPQSPGDFKC-7.5194-8.5547
HLA-A11:014UQ28221RSGSAPQSPGDFKC-6.9601-7.0735
HLA-A24:025HGA8221RSGSAPQSPGDFKC-7.52403-7.63743
HLA-A24:025HGA8221RSGSAPQSPGDFKC-5.82433-6.85963
HLA-B27:056PYJ8221RSGSAPQSPGDFKC-3.28285-4.31815
HLA-B44:053DX88221RSGSAPQSPGDFKC-5.91172-6.94702
HLA-B44:053DX88221RSGSAPQSPGDFKC-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of NEO1-DPP8

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
NEO1-DPP8chr1573345146chr1565766626918SAPQSPGDFCGCAGTCCCCAGGTGATTTCAAGTGTC

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 NEO1-DPP8

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
PRADNEO1-DPP8chr1573345146ENST00000261908chr1565766626ENST00000300141TCGA-EJ-7327

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Potential target of CAR-T therapy development for NEO1-DPP8

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 NEO1-DPP8

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 NEO1-DPP8

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