FluKB: A Knowledge-Based System for Influenza Vaccine Target Discovery and Analysis of the Immunological Properties of Influenza Viruses.

Christian Simon,Ulrich J Kudahl,Jing Sun,Ellis L Reinherz,Guang Lan Zhang,Lars Rønn Olsen,Vladimir Brusic

doi:10.1155/2015/380975

Abstract

FluKB is a knowledge-based system focusing on data and analytical tools for influenza vaccine discovery. The main goal of FluKB is to provide access to curated influenza sequence and epitope data and enhance the analysis of influenza sequence diversity and the analysis of targets of immune responses. FluKB consists of more than 400,000 influenza protein sequences, known epitope data (357 verified T-cell epitopes, 685 HLA binders, and 16 naturally processed MHC ligands), and a collection of 28 influenza antibodies and their structurally defined B-cell epitopes. FluKB was built using a modular framework allowing the implementation of analytical workflows and includes standard search tools, such as keyword search and sequence similarity queries, as well as advanced tools for the analysis of sequence variability. The advanced analytical tools for vaccine discovery include visual mapping of T- and B-cell vaccine targets and assessment of neutralizing antibody coverage. FluKB supports the discovery of vaccine targets and the analysis of viral diversity and its implications for vaccine discovery as well as potential T-cell breadth and antibody cross neutralization involving multiple strains. FluKB is representation of a new generation of databases that integrates data, analytical tools, and analytical workflows that enable comprehensive analysis and automatic generation of analysis reports.

Highlights

An estimated 250,000–500,000 people die from seasonal influenza infection each year
A huge body of sequence data, annotations, and knowledge is available in the literature, online resources, and biological databases such as GenBank [2], UniProt [3], Protein Data Bank [4], EpiFlu Database [5], OpenFlu Database [6], Influenza Research Database (IRD) [7], and the Immune Epitope Database (IEDB) [8]
The web-accessible interface uses a set of graphical user interface forms. These interfaces access search routines, analytical tools, and workflows that use a combination of PHP, Perl, Common Gateway Interface (CGI), and C background software

Summary

Introduction

An estimated 250,000–500,000 people die from seasonal influenza infection each year. The economic impact of influenza is immense due to the large number of lost working hours, hospitalizations, further medical complications, and treatment costs. Numerous computational analysis tools that are useful for vaccine target discovery are available They include keyword and text search tools, sequence comparison tools such as the BLAST algorithm [13] or multiple sequence alignment tools such as MAFFT [14], MUSCLE [15], and the Clustal [16], 3D structure visualization tools [17, 18], HLA binding prediction algorithms [19,20,21], and conservation analysis tools [22, 23], among others. FluKB is a knowledge-based system that integrates multiple types of influenza data and analytical tools into such workflows to support vaccine target discovery.

Materials and Methods

FluKB Database

FluKB Tools

Findings

Conclusion