PMID- 18315850
OWN - NLM
STAT- MEDLINE
DCOM- 20080411
LR  - 20240414
IS  - 1471-2105 (Electronic)
IS  - 1471-2105 (Linking)
VI  - 9 Suppl 1
IP  - Suppl 1
DP  - 2008
TI  - Hotspot Hunter: a computational system for large-scale screening and selection of 
      candidate immunological hotspots in pathogen proteomes.
PG  - S19
LID - 10.1186/1471-2105-9-S1-S19 [doi]
AB  - BACKGROUND: T-cell epitopes that promiscuously bind to multiple alleles of a 
      human leukocyte antigen (HLA) supertype are prime targets for development of 
      vaccines and immunotherapies because they are relevant to a large proportion of 
      the human population. The presence of clusters of promiscuous T-cell epitopes, 
      immunological hotspots, has been observed in several antigens. These clusters may 
      be exploited to facilitate the development of epitope-based vaccines by selecting 
      a small number of hotspots that can elicit all of the required T-cell activation 
      functions. Given the large size of pathogen proteomes, including of variant 
      strains, computational tools are necessary for automated screening and selection 
      of immunological hotspots. RESULTS: Hotspot Hunter is a web-based computational 
      system for large-scale screening and selection of candidate immunological 
      hotspots in pathogen proteomes through analysis of antigenic diversity. It allows 
      screening and selection of hotspots specific to four common HLA supertypes, 
      namely HLA class I A2, A3, B7 and class II DR. The system uses Artificial Neural 
      Network and Support Vector Machine methods as predictive engines. Soft computing 
      principles were employed to integrate the prediction results produced by both 
      methods for robust prediction performance. Experimental validation of the 
      predictions showed that Hotspot Hunter can successfully identify majority of the 
      real hotspots. Users can predict hotspots from a single protein sequence, or from 
      a set of aligned protein sequences representing pathogen proteome. The latter 
      feature provides a global view of the localizations of the hotspots in the 
      proteome set, enabling analysis of antigenic diversity and shift of hotspots 
      across protein variants. The system also allows the integration of prediction 
      results of the four supertypes for identification of hotspots common across 
      multiple supertypes. The target selection feature of the system shortlists 
      candidate peptide hotspots for the formulation of an epitope-based vaccine that 
      could be effective against multiple variants of the pathogen and applicable to a 
      large proportion of the human population. CONCLUSION: Hotspot Hunter is publicly 
      accessible at http://antigen.i2r.a-star.edu.sg/hh/. It is a new generation 
      computational tool aiding in epitope-based vaccine design.
FAU - Zhang, Guang Lan
AU  - Zhang GL
AD  - Institute for Infocomm Research, 21 Heng Mui Keng Terrace, Singapore 119613. 
      guanglanzhang@gmail.com
FAU - Khan, Asif M
AU  - Khan AM
FAU - Srinivasan, Kellathur N
AU  - Srinivasan KN
FAU - Heiny, At
AU  - Heiny A
FAU - Lee, Kx
AU  - Lee K
FAU - Kwoh, Chee Keong
AU  - Kwoh CK
FAU - August, J Thomas
AU  - August JT
FAU - Brusic, Vladimir
AU  - Brusic V
LA  - eng
GR  - U19 AI056541/AI/NIAID NIH HHS/United States
GR  - 5 U19 AI56541/AI/NIAID NIH HHS/United States
GR  - HHSN2662-00400085C/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - BMC Bioinformatics
JT  - BMC bioinformatics
JID - 100965194
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Proteome)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Epitope Mapping/*methods
MH  - Epitopes, T-Lymphocyte/*chemistry/*immunology
MH  - Immunodominant Epitopes/chemistry/immunology
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Proteome/*chemistry/*immunology
MH  - Sequence Analysis, Protein/*methods
PMC - PMC2259420
EDAT- 2008/03/20 09:00
MHDA- 2008/04/12 09:00
PMCR- 2008/02/13
CRDT- 2008/03/20 09:00
PHST- 2008/03/20 09:00 [pubmed]
PHST- 2008/04/12 09:00 [medline]
PHST- 2008/03/20 09:00 [entrez]
PHST- 2008/02/13 00:00 [pmc-release]
AID - 1471-2105-9-S1-S19 [pii]
AID - 10.1186/1471-2105-9-S1-S19 [doi]
PST - ppublish
SO  - BMC Bioinformatics. 2008;9 Suppl 1(Suppl 1):S19. doi: 10.1186/1471-2105-9-S1-S19.