Cancertope

In silico Platform for designing genome-based
Personalized immunotherapy or Vaccine against Cancer

Algorithm

  1. Data
    1. CanProVar Database
    2. CCLE database
    3. Distribution of frequently mutated genes in CCLE database
  2. Prediction algorithms
    1. ABCpred
    2. ProPred: MHC II binder prediction
    3. ProPred1: MHC I binder prediction
    4. CTLPred: CTL epitope prediction

Data


The mutation data is obtained from CCLE and CanProVar databases.


CanProVar database


We have adopted cancer associated deleterious mutations and general polymorphism from CanProVar database and calculated the ration of frequency of deleterious mutations (fD) over general polymorphism (fP). Such 36 genes showing high ratio (fD/fP) have been selected for mutation and immune epitope analysis..


TargetUniProt IDRefSeq IDDeleterious Mutation Freq (fD)Polymorphism Freq (fP)Ratio (fD/fP)Family
PTEN P60484 NM_000314 389 1 389 NA
TP53 P04637 NM_001126112 1353 7 193.3 P53_family
CTNNB1 P35222 NM_001904 132 1 132 Beta-catenin_family
BRAF P15056 NM_004333 99 1 99 Protein_kinase_superfamily,_TKL_Ser/Thr_protein_kinase_family,_RAF_subfamily
NF2 P35240 NM_000268 74 1 74 NA
EGFR P00533 NM_005228 188 3 62.7 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_EGF_receptor_subfamily
SMAD4 Q13485 NM_005359 107 2 53.5 Dwarfin/SMAD_family
SMAD4 Q13485 NM_005359 107 2 53.5 Dwarfin/SMAD_family
VHL P40337 NM_000551 272 6 45.3 NA
KIT P10721 NM_000222 131 3 43.7 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_CSF-1/PDGF_receptor_subfamily
PIK3CA P42336 NM_006218 174 4 43.5 PI3/PI4-kinase_family
NRAS P01111 NM_002524 36 1 36 Small_GTPase_superfamily,_Ras_family
MSH2 P43246 NM_000251 103 5 20.6 DNA_mismatch_repair_MutS_family
GATA1 P15976 NM_002049 20 1 20 NA
MLH1 P40692 NM_000249 118 6 19.7 DNA_mismatch_repair_MutL/HexB_family
FBXW7 Q969H0 NM_033632 67 4 16.8 NA
MEN1 O00255 NM_130800 49 3 16.3 NA
FGFR3 P22607 NM_001163213 31 2 15.5 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_Fibroblast_growth_factor_receptor_subfamily
TSHR P16473 NM_000369 46 3 15.3 G-protein_coupled_receptor_1_family,_FSH/LSH/TSH_subfamily
JAK2 O60674 NM_004972 40 3 13.3 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_JAK_subfamily
RB1 P06400 NM_000321 102 8 12.8 Retinoblastoma_protein_(RB)_family
PDGFRA P16234 NM_006206 35 3 11.7 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_CSF-1/PDGF_receptor_subfamily
NF1 P21359 NM_001042492 65 6 10.8 NA
FGFR2 P21802 NM_022970 43 4 10.8 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_Fibroblast_growth_factor_receptor_subfamily
FLT3 P36888 NM_004119 35 4 8.8 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_CSF-1/PDGF_receptor_subfamily
CDH1 P12830 NM_004360 68 8 8.5 NA
TNFAIP3 P21580 NM_006290 31 4 7.8 Peptidase_C64_family
CBL P22681 NM_005188 30 4 7.5 NA
RET P07949 NM_020975 58 8 7.3 Protein_kinase_superfamily,_Tyr_protein_kinase_family
MSH6 P52701 NM_000179 40 8 5 DNA_mismatch_repair_MutS_family
ERBB2 P04626 NM_004448 29 6 4.8 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_EGF_receptor_subfamily
MET P08581 NM_001127500 23 5 4.6 Protein_kinase_superfamily,_Tyr_protein_kinase_family
ABL1 P00519 NM_007313 23 7 3.3 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_ABL_subfamily
ALK Q9UM73 NM_004304 27 9 3 Protein_kinase_superfamily,_Tyr_protein_kinase_family,_Insulin_receptor_subfamily
ATM Q13315 NM_000051 134 52 2.6 PI3/PI4-kinase_family,_ATM_subfamily

CCLE database


In other approach we looked at most frequent mutations in the CCLE database. In this study we looked at those mutations which were found in at least 10% of total cell lines (905)..


TargetUniProt IDRefSeq IDFamily
AAK1 Q2M2I8 NM_014911 Protein kinase superfamily, Ser/Thr protein kinase family
AKAP12 Q02952 NM_005100 NA
AKAP12 Q86TJ9 NM_005100 NA
AKAP9 Q99996 NM_005751 NA
AKAP9 Q5GIA7 NM_005751 NA
AKAP9 Q6PJH3 NM_005751 NA
ALPK2 Q86TB3 NM_052947 Protein kinase superfamily, Alpha-type protein kinase family, ALPK subfamily
CARD10 Q9BWT7 NM_014550 NA
CHD1 B3KT33 NM_001270 NA
CHD1 O14646 NM_001270 SNF2/RAD54 helicase family
CREB3L2 Q68D60 NM_194071 NA
CREB3L2 Q70SY1 NM_194071 BZIP family, ATF subfamily
CTBP2 P56545 NM_022802 D-isomer specific 2-hydroxyacid dehydrogenase family
FMN2 Q9NZ56 NM_020066 Formin homology family, Cappuccino subfamily
FMN2 Q9HBL1 NM_020066 NA
GPR112 Q8IZF6 NM_153834 G-protein coupled receptor 2 family, LN-TM7 subfamily
HSP90B1 V9HWP2 NM_003299 NA
HSP90B1 P14625 NM_003299 Heat shock protein 90 family
MAML2 Q8IZL2 NM_032427 Mastermind family
MAP3K1 Q13233 NM_005921 Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
MAP3K4 Q9P1M2 NM_005922 NA
MAP3K4 Q9Y6R4 NM_005922 Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
MLL3 Q8NEZ4 NM_170606 Class V-like SAM-binding methyltransferase superfamily, Histone-lysine methyltransferase family, TRX/MLL subfamily
MSH3 P20585 NM_002439 DNA mismatch repair MutS family, MSH3 subfamily
MYLK Q15746 NM_053025 Protein kinase superfamily, CAMK Ser/Thr protein kinase family
MYST4 Q8WYB5 NM_012330 MYST (SAS/MOZ) family
MYST4 B2RWN8 NM_012330 NA
NCOA3 Q9Y6Q9 NM_181659 SRC/p160 nuclear receptor coactivator family
NR1H2 P55055 NM_007121 Nuclear hormone receptor family, NR1 subfamily
NR1H2 F1D8P7 NM_007121 Nuclear hormone receptor family
PDE4DIP Q5VU43 NM_014644 NA
PIK3C2G B7ZLY6 NM_004570 NA
PIK3C2G O75747 NM_004570 PI3/PI4-kinase family
PRKDC P78527 NM_006904 PI3/PI4-kinase family
RECQL4 O94761 NM_004260 Helicase family, RecQ subfamily
TNRC6B Q9UPQ9 NM_001162501 GW182 family
TTBK1 Q5TCY1 NM_032538 Protein kinase superfamily, CK1 Ser/Thr protein kinase family

Distribution of frequently mutated genes in CCLE database:


algo2.png


Prediction Algorithms


CTLPred      Link


CTLPred is a direct method for prediction of CTL epitopes crucial in subunit vaccine design.In direct methods the information or patterns of T cell epitopes instead of MHC binders were used for the development o f methods. The methods is based on elegant machine learning techniques like Artificial Neural network.


ProPred1      Link


The ProPred-I is an on-line service for identifying the MHC Class-I binding regions in antigens. It implements matrices for 47 MHC Class-I alleles, proteasomal and immunoproteasomal models. The main aim of this server is to help users in identifying the promiscuous regions.


ProPred      Link


The aim of this server is to predict MHC Class-II binding regions in an antigen sequence, using quantitative matrices derived from published literature by Sturniolo et. al., 1999. The server will assist in locating promiscuous binding regions that are useful in selecting vaccine candidates.


LBTope      Link

The aim of LBTope server is to predict B cell epitope(s) in an antigen sequence, using Support Vector Machine as machine learning method.


CANCERTOPE    |     Raghava's Group    |     IMTECH    |     CSIR    |     CRDD    |     GPSR Package