Pathogen Genome Cluster Computing

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Synteny maps between the genomes of T. brucei and L. major with different colours representing blocks of synteny between the 11 chromosomes of T. brucei and 36 chromosomes of Leishmania. Reproduced with permission from El-Sayed et al., Science 309: 406, Fig. 2 © 2005 AAAS. Permission from AAAS is required for all other uses.

A genome is the complete complement of DNA for an organism. Complete genome sequences are available for many pathogenic bacteria including Mycobacterium tuberculosis, Yersina pestis (plague), Clostridium difficile and intestinal pathogens such as Campylobacter jejini, Helicobacter and enteric Yersina.

The genome projects for eukaryotic pathogens are a research paradigm in the making. The genomes for Plasmodium falciparum, P. yoelii yoelii, Entamoeba histolytica, Crytosporidium homis and C. parvum are complete at the time of writing.

The most recently completed genomes were the three medically important trypansomatids, Trypanosoma brucei, T. cruzi and Leishmania, known as the "TriTryps" (Science 309: complete issue). The TriTryps in many ways heralds the dawn of the protozoan pathogen genome era in comparative genomics

Bioinformatics and Phylogenomics

Bioinformatics is simply the application of computer algorithms to understand molecular data. Most bioinformatic programs are orientated around DNA sequence data.

Applying bioformatics software to understand two or more related genomes delves into the area of comparative genomics. When three or more genomes are compared hardcore phylogenetics analysis can be performed on a genomics scale, which is otherwise known as phylogenomics.

Comparative genomic approaches are powerful because detailed comparisons between genomes reveal important genetic anomalies that occur within a genome. A simple example is calculating variations in the rate of amino acid mutation throughout a genome to identify potential vaccine candidates.

© SEM of T. brucei of by Michael Smith, LSHTM

T. cruzi infected heart tissue. Castro Sila, Memorias

Microarray genomics



Phylogenomics is not restricted to DNA sequence data at LSHTM. DNA-DNA microarray analysis is popular targets for analysis, which is increasingly, processed using Bayesian approaches. An example showing a basic distance tree reconstructed using a simple clustering algorithm under a 'molecular clock' assumption is shown in the diagram opposite.

Proteomic analysis is currently an experimental area of methodological investigation and analysed using network-based phylogenomics.

Complex examples of all the analytical areas described will be presented following publication, although there are currently no plans to work on Cryptosporidium.

Simple GeneSpring analysis of C. jejuni DNA-DNA microarry by Olivia Champion

Schematic analysis of Y. pestis genome by Brendan Wren

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Comments and enquiries Last updated 28th July, 2005 MWG.