Pathogen Populations - Tools
IDEA (Interactive Display for Evolutionary Analyses) provides a graphical interface for PAML (Phylogenetic Analysis by Maximum Likelihood, Ziheng Yang, 1997), a suite of programs for conducting molecular evolution analyses on nucleotide and amino-acid data. IDEA allows you to run either of the PAML programs codeml or baseml on a single dataset or on multiple datasets simultaneously. Among other things, codeml and baseml allow you to obtain maximum likelihood estimates of numbers of substitutions per branch and per site and to compare multiple models of molecular evolution given the data and a phylogenetic tree for the sequences. IDEA runs on Linux, Solaris and Mac OS X operating systems; it is designed to execute processes in parallel on a multiprocessor machine and can run on a computer grid with either SGE or Condor. IDEA is available free of charge from SourceForge.
A new tool for large-scale reverse vaccinology
I have a long track record of developing computational and analytical approaches to support translational efforts aimed at developing new vaccines and therapeutics. In collaboration with the team of Dr. Rino Rappuoli at GlaxoSmithKline (former Chiron Vaccines and Novartis Vaccines and Diagnostics), I leveraged bacterial genome information to pioneer the Reverse Vaccinology approach that identifies and prioritizes novel vaccine candidates using whole genome sequencing. We recently developed an updated reverse vaccine ology pipeline, ReVac, that implements both a panoply of feature prediction programs without filtering out proteins, and scoring of candidates based on predictions made on curated positive and negative control protein datasets. ReVac surveys several genomes assessing protein conservation, as well as DNA and protein repeats, which may result in variable expression of potential vaccine candidates (PVCs). ReVac’s orthologous clustering of conserved genes, identifies core and dispensable genome components. ReVac’s use of a scoring scheme ranks PVCs for subsequent experimental testing. Application of ReVac to two COPD pathogens prioritized PVCs, identifying both novel and previously validated PVCs.
[PI: Hervé, collaborator: Tim Murphy again]
Parasite genomics resources
As part of these and previous parasite-focused projects, we have generated online genomics resources for Theileria parva , a parasite that causes East Coast Fever in cattle, and the human parasite Cryptosporidium hominis. These resources allow the user to search each parasite genome for proteins that satisfy several criteria important in the selection of viable vaccine candidates.