MLW Pathogen Genomics studies

Dr. Sarah White, University of Malawi, College of Medicine, Blantyre

Ubuntunet contact: Margaret Ngwira

Malawi-Liverpool-Wellcome Trust Clinical Research Programme (MLW), University of Malawi, College of Medicine, Blantyre (www.mlw.medcol.mw)

swhite@mlw.medcol.mwmengwira@ubuntunet.net

Define population structure, genetic epidemiology, markers of drug resistance and diversifying selection, potential vaccine candidates for bacterial and protozoan pathogens and the impact of HIV on genetic diversity.

Whole genome sequencing, 16S analysis and microarray analysis. The analysis is computing intensive using bioinformatic and phylogenetic packages to interrogate the data.  Most software utilised has been developed by WTSI (www.sanger.ac.uk/Software/).     

Genome sequence assembly is performed at WTSI and the majority of comparative bioinformatic analyses are performed at MLW.  The studies are using pathogen genomes to study population structures and answer a series of clinical and epidemiologically relevant questions both locally and across sub-Saharan Africa. The research activity makes use of both locally generated genetic information and the wealth of gene sequence data on publicly available databases  accessible over the internet.. 

The main data generated by these studies includes:

• Whole genome sequence data

• SNP haplotyping

• Phylogenetic trees

• Microarray data in various outputs

For the malaria study, data will be linked to diagnosis (severe/uncomplicated malaria), multiplicity of infection and to seasonality.  As this is a longitudinal study, there will also be analyses of sequential infections in individual patients.

The malaria study recruits from a double-blinded study of efficiency and efficacy of two artemisinin-combination therapies.  The data can therefore be analysed in the context of treatment arm following unblinding of the study.

Artemis/ACT/BLAST/E-burst/PHYml/LookSeq/MapSeq

Several of the tools uses are web-based and require a robust internet connection.

Most work done remotely on WTSI server, as no storage capacity locally to hold massive Gigabyte output from sequencing. Most analyses run overnight as connection speed poor during working hours.

Most of the analysis will be performed locally by PhD students with logistical support from MLW ICT team.

Cost-Benefit analysis of access to e-infrastructure resources

Economic efficiency

Running / Recurring cost reduction  and elimination of costs of data media (Disks)

More funding to research grants

Facilitates mentoring and e-conferencing

Operational efficiency 

Strengthen position of local scientists with cutting edge science

Enough capacity to handle volumes of research data

Time saving

Enhance speedy and quality research

Real-time discussions forum (including webninars) via video/voice conferencing over IP

Accessibility

Reduction of potential risks of unauthorised access to confidential data

No portable media required

Environmental impact

Reduced travel needs

e-Infrastructure potential

Available infrastructure include six Internet Service Providers (ISPs)  Services provided include wireless Connection (VSAT), Leased Lines, Dial up Connection, GPRS (Zain & Telekom). Connection speeds typically  64 Kbps to 1 Mbps (Max). Costs of connection are prohibitive ~1 USD / minute.

The limitations include exorbitant costs of bandwidth, scanty regional ICT collaborations and ragmented regional ICT infrastructural policies

The consequences include frustration of  local scientists and risk for brain-drain, limited replication of results, withdrawal of Research Grants, no ICT capacity to support big research innovations, disjointed (void) brainstorming sessions among regional scientists, absence of real-time  scientific discussion groups, major scientific discoveries lag behind 

Genomic research needs top of the range ICT infrastructure,Development of vaccines against endemic diseases. Without this infrastructure, the wealth of genomic information currently available will largely be exploited by research groups in industrialised countries rather than the environment from where it has come.