A Resource Report on Curatopes Melanoma was published in Cancer Research:
Lischer C, Eberhardt M, Jaitly T, Schinzel C, Schaft N, Dörrie J, Schuler G, and Vera J. Curatopes Melanoma: a database of predicted T-cell epitopes from overly expressed proteins in metastatic cutaneous melanoma. Cancer Res. 2019 Aug 15. [Epub ahead of print] PMID: 31416842. doi: 10.1158/0008-5472.CAN-19-0296.
The four available tables are Superior tolerance (predicted), Enhanced tolerance (predicted), All predicted epitopes, and Known melanoma epitopes. Superior tolerance (predicted) and Enhanced tolerance (predicted) are subsets of All predicted epitopes.
We based our analysis on a set of 32 metastatic cutaneous melanoma biopsies (all samples but GSM2069836 from GEO dataset GSE78220, and samples GSM2536673, -675, -677, -679, and -681 from GEO dataset GSE96619) and on tissue profiles from the Human Protein Atlas and the GTEx transcriptome set. All epitopes are annotated with relevant features and a score was calculated to rank epitopes according to their expected clinical performance.
Annotated human protein sequences were obtained from Ensembl (release 94). Epitopes were predicted from these sequences with the offline-version of IEDB tools leveraging the included Python script using artificial neural networks and netMHCpan version 4.0.
Below the table headers, you will see empty boxes. Each of these boxes can be used to filter the corresponding column based on values that you specify, and multiple columns can be filtered against simultaneously.
Below each table, you will find two buttons: filtering.
and . The latter will always download the complete table that you are currently inspecting while the former will download the collection of epitopes from that table that you have set up viaAmong the predicted epitope features are binding affinity (between peptide and the HLA molecule) and immunogenicity (i.e., T-cell receptor engagement). These two features were combined with the observed median transcript expression and the gene expression index in melanoma biopsies to calculate the gPIE score.
In an intial step, binding affinity, immunogenicity, and median transcript expression were normalized to the value range between 0 and 1. The product of the normalized values was then multiplied with the gene expression index and with 100 to make the values more readable. See the formulas below for the exact mathematical treatment. $$ gPIE_{Epitope} = 100 \cdot f_1(BindAff_{Epitope}) \cdot f_2(Immunog_{Epitope}) \cdot f_3(MelTranscExp_{Peptide}) \cdot f_4(GeneExpIndex_{Peptide})$$ $$ f_1(BindAff_{Epitope}) = \frac{-BindAff_{Epitope} - min(-BindAff)}{max(-BindAff) - min(-BindAff)} = \frac{BindAff_{Epitope} - max(BindAff)}{min(BindAff) - max(BindAff)} $$ $$ f_2(Immunog_{Epitope}) = \frac{Immunog_{Epitope} - min(Immunog)}{max(Immunog) - min(Immunog)} $$ $$ f_3(MelTranscExp_{Peptide}) = \begin{cases} \frac{MelTranscExp_{Peptide}}{100} &\quad \text{if MelTranscExp}_{Epitope} \lt 100 \\ 1 &\quad\text{otherwise} \\ \end{cases} $$ $$ f_4(GeneExpIndex_{Peptide}) = \frac{MelGeneExp_{Peptide}} {MelGeneExp_{Peptide} + MaxTissueGeneExp_{Peptide}} $$ The gene expression values in f4 are the ones listed in the two table colums Lower-bound Tumor Gene Expression and Max Upper-bound Tissue Gene Expression. The achievable minimum and maximum of the gPIE score are 0 and 100, respectively.
Peptides from these genes are found in the corresponding tables:
Gene Symbol | Gene Name | Superior tolerance (predicted) | Enhanced tolerance (predicted) | All predicted epitopes | Known melanoma epitopes |
---|---|---|---|---|---|
ATOX1 | antioxidant 1 copper chaperone | yes | yes | ||
C11orf71 | chromosome 11 open reading frame 71 | yes | yes | ||
CDKN2A | cyclin-dependent kinase inhibitor 2A | yes | |||
CLPP | caseinolytic mitochondrial matrix peptidase proteolytic subunit | yes | |||
COX7A2L | cytochrome c oxidase subunit VIIa polypeptide 2 like | yes | yes | ||
CSNK1A1 | casein kinase 1, alpha 1 | yes | |||
CSNK2A3 | casein kinase 2, alpha 3 polypeptide | yes | yes | ||
CTAG1B | cancer/testis antigen 1B | yes | |||
DCT | dopachrome tautomerase | yes | |||
ELOC | elongin C | yes | yes | ||
FOLH1 | folate hydrolase (prostate-specific membrane antigen) 1 | yes | |||
GAS7 | growth-arrest-specific 7 | yes | |||
GPR143 | G-protein-coupled receptor 143 | yes | |||
GPR89A | G-protein-coupled receptor 89A | yes | yes | ||
GPR89B | G-protein-coupled receptor 89B | yes | yes | ||
GTF2H2C | GTF2H2 family member C | yes | yes | ||
HAUS3 | HAUS augmin-like complex, subunit 3 | yes | |||
HSBP1 | heat-shock-factor-binding protein 1 | yes | yes | ||
KRTCAP2 | keratinocyte-associated protein 2 | yes | yes | ||
MAGEA3 | melanoma antigen family A3 | yes | yes | ||
MCTS1 | malignant T-cell-amplified sequence 1 | yes | yes | ||
MLANA | melan-A | yes | |||
MPLKIP | M-phase-specific PLK1 interacting protein | yes | yes | ||
MRPS33 | mitochondrial ribosomal protein S33 | yes | yes | ||
NACA | nascent polypeptide-associated complex alpha subunit | yes | yes | ||
NBPF20 | neuroblastoma breakpoint family, member 20 | yes | yes | ||
NDUFA11 | NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 11, 14.7kDa | yes | yes | ||
PCLAF | PCNA-associated factor | yes | yes | ||
PGAM4 | phosphoglycerate mutase family member 4 | yes | yes | ||
PIGF | phosphatidylinositol glycan anchor biosynthesis, class F | yes | yes | ||
PMEL | premelanosome protein | yes | |||
PPP1R3B | protein phosphatase 1, regulatory subunit 3B | yes | |||
PRAME | preferentially expressed antigen in melanoma | yes | |||
PSMG4 | proteasome (prosome, macropain) assembly chaperone 4 | yes | yes | ||
RAB38 | RAB38, member RAS oncogene family | yes | |||
RAMACL | RNA guanine-7 methyltransferase-activating subunit-like (pseudogene) | yes | yes | ||
RAN | RAN, member RAS oncogene family | yes | yes | ||
RIOX1 | ribosomal oxygenase 1 | yes | yes | ||
RPL37 | ribosomal protein L37 | yes | yes | ||
RPS19 | ribosomal protein S19 | yes | yes | ||
RPS27L | ribosomal protein S27-like | yes | yes | ||
SERF2 | small EDRK-rich factor 2 | yes | yes | ||
SMIM10L1 | small integral membrane protein 10 like 1 | yes | yes | ||
SMUG1 | single-strand-selective monofunctional uracil-DNA glycosylase 1 | yes | yes | ||
TIMM23B | translocase of inner mitochondrial membrane 23 homolog B (yeast) | yes | yes | ||
TMBIM4 | transmembrane BAX inhibitor motif-containing 4 | yes | yes | ||
TRAPPC9 | trafficking protein particle complex 9 | yes | yes | ||
TXNL4A | thioredoxin-like 4A | yes | yes | ||
TYR | tyrosinase | yes | |||
USP41 | ubiquitin-specific peptidase 41 | yes | yes |
We based our analysis on a list of 36 well-characterized HLA class I alleles that are common in the European population.
Our tissue analysis was based on the GTEx transcriptome set. We classified its 51 non-cell line tissues as either survival-crititcal or dispensable. The below table lists the tissues available in GTEx together with their number of biospecimens, whether they were used in our analysis (column Excluded) and whether we considered them critical for survival (column Survival-Critical).
Organ | Tissue | Available Specimens | Excluded | Survival-Critical |
---|---|---|---|---|
Adipose | Subcutaneous | 442 | - | - |
Visceral (Omentum) | 355 | - | - | |
Adrenal Gland | - | 190 | - | yes |
Artery | Aorta | 299 | - | - |
Coronary | 173 | - | yes | |
Tibial | 441 | - | - | |
Bladder | - | 11 | - | - |
Brain | Amygdala | 100 | - | yes |
Anterior cingulate cortex (BA24) | 121 | - | yes | |
Caudate (basal ganglia) | 160 | - | yes | |
Cerebellar Hemisphere | 136 | - | yes | |
Cerebellum | 173 | - | yes | |
Cortex | 158 | - | yes | |
Frontal Cortex (BA9) | 129 | - | yes | |
Hippocampus | 123 | - | yes | |
Hypothalamus | 121 | - | yes | |
Nucleus accumbens (basal ganglia) | 147 | - | yes | |
Putamen (basal ganglia) | 124 | - | yes | |
Spinal cord (cervical c-1) | 91 | - | yes | |
Substantia nigra | 88 | - | yes | |
Breast | Mammary Tissue | 290 | - | - |
Cervix | Ectocervix | 6 | - | - |
Endocervix | 5 | - | - | |
Colon | Sigmoid | 233 | - | yes |
Transverse | 274 | - | yes | |
Esophagus | Gastroesophageal Junction | 244 | - | yes |
Mucosa | 407 | - | yes | |
Muscularis | 370 | - | yes | |
Fallopian Tube | - | 7 | - | - |
Heart | Atrial Appendage | 297 | - | yes |
Left Ventricle | 303 | - | yes | |
Kidney | Cortex | 45 | - | yes |
Liver | - | 175 | - | yes |
Lung | - | 427 | - | yes |
Minor Salivary Gland | - | 97 | - | - |
Muscle | Skeletal | 564 | - | - |
Nerve | Tibial | 414 | - | - |
Ovary | - | 133 | - | - |
Pancreas | - | 248 | - | yes |
Pituitary | - | 183 | - | - |
Prostate | - | 152 | - | - |
Skin | Not Sun Exposed (Suprapubic) | 387 | - | - |
Sun Exposed (Lower leg) | 473 | - | - | |
Small Intestine | Terminal Ileum | 137 | - | yes |
Spleen | - | 162 | - | - |
Stomach | - | 262 | - | yes |
Testis | - | 259 | - | - |
Thyroid | - | 446 | - | - |
Uterus | - | 111 | - | - |
Vagina | - | 115 | - | - |
Whole Blood | - | 407 | - | yes |
- | EBV-transformed lymphocytes | 130 | yes | - |
Leukemia cell line (CML) | 0 | yes | - | |
Transformed fibroblasts | 343 | yes | - |