MRC/UVRI Medical Informatics Centre

Lead Research Organisation: MRC/UVRI Uganda Research Unit on AIDS

Abstract

Collating information on human health and disease, and understanding the biological processes that may cause disease can help identify ways to develop new treatments for these diseases. The use of complex statistics, computational resources and genetic information has greatly facilitated our understanding of human disease. For Africa to fully benefit from the technological advances in computing and ways to store and manage "big scientific data", we will need to ensure that African researchers have access to such resources locally. As part of an international collaboration, we aim to build a computational network and resource in Uganda, and train the next generation of African computer scientists as part of this initiative. This project will help facilitate our understanding on diseases in Africa and also provide a way to assess changes in the prevalence of these diseases, including HIV and other chronic diseases such as diabetes.

Technical Summary

The integration of epidemiological methods-including large-scale, multi-centre studies and pooled analyses of observational and interventional studies-with genomic and computational technologies has provided new insights into the biology of a broad range of diseases, including human and pathogen genomic diversity, and their risk factors. These advances in genomics create new opportunities and challenges for researchers in sub-Saharan Africa (SSA). Given the marked genomic diversity among human and pathogen populations in SSA,1,2 understanding the genomic basis of these diseases and their risk factors in populations of African descent will provide: 1) additional insights into disease aetiology; 2) new opportunities for disease surveillance; and 3) potential therapeutic and public health intervention strategies. If countries in SSA are to benefit from developments in genomics and medical informatics, there is a need to strengthen capacity, training and collaboration across the region, and with northern partners, to ensure SSA researchers can play a full part. To capitalise on these technological advances and to ensure the efficient utilisation of data resources in clinical epidemiology and large scale genomics across SSA from existing and on-going research programmes, and as part of the MRC/UVRI Uganda Research Unit on AIDS, we propose to develop the MRC/UVRI Medical Informatics Centre (MIC) in Entebbe, Uganda (panel 1). The planned centre will house a computer cluster and build on established strategic collaborations with UK research centres. These UK centres will provide scientific and logistical support to develop infrastructure and computational processes, cloud computing and human research capacity, as well as supporting pan-African and north-south research partnerships (Africa-UK medical informatics consortium).

Planned Impact

The integration of epidemiological methods-including large-scale, multi-centre studies and pooled analyses of observational and interventional studies-with genomic and computational technologies has provided new insights into the biology of a broad range of diseases, including human and pathogen genomic diversity, and their risk factors. These advances create new opportunities and challenges for researchers in SSA. If countries in SSA are to benefit from developments in genomics and medical informatics, there is a need to strengthen capacity, training and collaboration across the region, and with northern partners, to ensure SSA researchers can play a full part. The proposed MRC/UVRI Medical Informatics Centre in Entebbe will create opportunities to capitalise on these technological advances and to ensure the efficient utilisation of data resources in clinical epidemiology and large scale genomics across SSA from existing and on-going research programmes.

The data centre will allow for harmonised data storage, management and access across centres. Through establishing a centralised bioinformatics infrastructure, a broad spectrum of scientific studies will be supported. This approach will also provide a sustainable model, accessible by a broad scientific community spanning epidemiology, genomics and public, for both infectious and non-infectious diseases. We aim to enhance existing capacity through the expansion of the existing network and server system and with the addition of a full-time data manager. The research community - particularly researchers working in African centres - will benefit from this investment in training and infrastructure; thus the data centre will provide an excellent framework to develop a sustainable international research programme in SSA.

There will be multiple beneficiaries linked to this planned medical informatics centre in Uganda. These beneficiaries include: 1) the national government--the Ugandan Ministry of Health is an active supporter of the proposed initiative, and will directly benefit from the resource in the context of disease surveillance and analyses to inform public health policy; 2) regional research and educational institutes--local research institutes and universities will have access to the proposed computational resource to facilitate their research and operational programmes; 3) the next generation of African computational scientists and research leaders--as part of an integrated programme of research capacity and training linking several pan-African capacity building initiatives; and 4) the wider scientific community--with a framework for governance and data access and sharing the planned medical informatics centre will provide access to data for global initiatives to facilitate a step change in human health research.

No direct commercial exploitation is anticipated.

Publications

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Bugembe D (2020) Main Routes of Entry and Genomic Diversity of SARS-CoV-2, Uganda in Emerging Infectious Diseases

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Bugembe DL (2021) SARS-CoV-2 Variants, South Sudan, January-March 2021. in Emerging infectious diseases

 
Description Guidance on HIV hot spots and direction of transmission
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact This has helped in understanding which are the hot spots for HIV, for example we showed that though fishing communities have high HIV prevalence they are not the main source of HIV transmissions in the general population. This has influenced on how prevention is done to spread beyond concentrating on the fishing communities. This has led to better HIV prevention in Uganda
 
Description SARSCoV2 variants in Uganda for proper vaccination planning
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact This work has guided on the selection of vaccines for SARSCoV2
 
Description Understanding the cirsulating HIV strains in Uganda
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact By describing and providing information on the circulating HIV subtypes in Uganda, this information is used in HIV vaccine design and treatment. The vaccine, monoclonal antibodies and drugs developed have to be relevant in terns of the HIV strains they target. We are seeing an increase in the proportion of HIV recombinant viruses in Uganda.
 
Description EDCTP
Amount € 3,000,000 (EUR)
Organisation European Union 
Sector Public
Country European Union (EU)
Start 03/2017 
End 03/2020
 
Description MRC Informatics
Amount £2,860,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 06/2014 
End 06/2019
 
Description MRC-Zika virus funding
Amount £150,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2016 
End 03/2018
 
Description NIH RO1
Amount $650,000 (USD)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 02/2015 
End 01/2020
 
Description Phylogenetics Networks to Address Transmission of HIV (PANGEA)
Amount $300,000 (USD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 09/2014 
End 02/2017
 
Title African Affimatrix 
Description The genomic data from the General Population Cohort will contribute to the Affimatrix technology 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact This will allow scientists to identify unique genes associated with diseases 
 
Title Bioinformatics 
Description Servers, computers, internet connections, soft ware for analyses of genomes 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact Increased capacity to analyze large sequence data 
 
Title Computational MHC-I epitope predictor that dentifies 95% of experimentally mapped HIV-1 clade A and D epitopes 
Description We tested the performance of the NetMHCpan4.0 computational neural network in re-identifying 93 T-cell epitopes that had been previously independently mapped using the whole proteome IFN-? ELISPOT assays in 6 HLA class I typed Ugandan individuals infected with HIV-1 subtypes A1 and D. We found this to be a very good tool 
Type Of Material Improvements to research infrastructure 
Year Produced 2020 
Provided To Others? Yes  
Impact NetMHCpan4.0 class I epitope predictions covered 95% of the epitope responses and would reduce the number of experimental confirmatory tests by > 80%. Algorithmic epitope prediction in conjunction with HLA allele frequency information can cost-effectively assist immunogen design through minimizing the experimental effort. 
 
Title HIV-1 Gag-Pol Sequences from Ugandan Early Infections Associated with Elevated Replication Capacity 
Description Using a novel protein domain approach, we documented differences in the Gag-p6 domain that were frequently associated with higher in HIV vitro replication. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2021 
Provided To Others? Yes  
Impact This observation has potential for additional HIV therapeutic approaches 
 
Title We identiied novel gene loci associated with anthropometric, hematological, lipid, and glycemic traits in African populations 
Description In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2019 
Provided To Others? Yes  
Impact These results have potential to find ways to predict disease risks and interventions 
 
Description Collaboration is assay development and data analysis 
Organisation University of Glasgow
Department MRC - University of Glasgow Centre for Virus Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Patient recruitment, Data generation and analysis
Collaborator Contribution Assay development, analysis and manuscript drafting
Impact Capacity building in data analysis Publications Funding
Start Year 2017
 
Description Dual and superinfection studies 
Organisation University of Alabama at Birmingham
Department School of Medicine
Country United States 
Sector Academic/University 
PI Contribution Generation of ideas and Proposal writting Looking for external funding Supervision
Collaborator Contribution Training Supervision of studentsTraining Supervision of students Paper manuscripts
Impact Training Supervision External funding
Start Year 2008
 
Description Dual and superinfection studies 
Organisation University of Cape Town
Country South Africa 
Sector Academic/University 
PI Contribution Generation of ideas and Proposal writting Looking for external funding Supervision
Collaborator Contribution Training Supervision of studentsTraining Supervision of students Paper manuscripts
Impact Training Supervision External funding
Start Year 2008
 
Description HIV molecular epidemiology 
Organisation University College London
Department MRC Centre for Medical Molecular Virology
Country United Kingdom 
Sector Academic/University 
PI Contribution Generation of research ideas, training, supervision and looking for additional external funding
Collaborator Contribution Training and supervision
Impact Training, supervision and looking for additional external funding
Start Year 2014
 
Description HIV transmission network studies 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We have together worked on a grant proposal to the Gates Foundation which has been funded and due to start in 2014
Collaborator Contribution We have together written grant application, and in the future will contribute to training
Impact Proposal writing New funding
Start Year 2014
 
Description HIV transmission network studies 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution We have together worked on a grant proposal to the Gates Foundation which has been funded and due to start in 2014
Collaborator Contribution We have together written grant application, and in the future will contribute to training
Impact Proposal writing New funding
Start Year 2014
 
Description Medical Informatics 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Training, publications, networking and additional funding
Collaborator Contribution Training, publications, networking and additional funding
Impact Training, publications, additional funding and networks
Start Year 2014
 
Description Metagenomics analyses with Glasgow University 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution We have provided specimens. We have received sequences generated at Glasgow for analysis at UVRI. We have participated in writing of new research grants. We have worked with the team to present data to the research community and to the local communities in West Nile where a new virus was isolated
Collaborator Contribution They have trained our staff in metagenomics, and contributed to the transfer of technology. Three of our staff have visited Glasgow and a team led by Dr Emma Thompson has also visited us. We are together writing other research grants
Impact In the process of looking for Zika virus, we have also identified other viruses including Le Dantec Rhabdovirus. Metagenomic analysis of the acute plasma RNA revealed a contiguous sequence of 11,423 nucleotides that had a 94% identity with a 1965 LDV strain isolated from a Senegalese girl (DakHD763 strain, KM205006) by phylogenetic analysis. The metagenomics sequence was confirmed by PCR and Sanger sequencing of a 5'-half genome fragment. We have also identified a new virus named Adumi virus, from a girl in West Nile region
Start Year 2015
 
Description Partnership with UVRI on Zika virus studies 
Organisation Uganda Virus Research Institute
Department Department of Arbovirology, Emerging and Re-emerging Infections
Country Uganda 
Sector Public 
PI Contribution We provide sequencing expertise and its analyses. We have provided facilities to analyse more samples. We have provided training opportunities to UVRI staff including those studying for MSc and PhD
Collaborator Contribution UVRI provides mosquito and human specimens to analyse. They also perform some other analyses such as the plaque neutralization reduction assays, and characterization of the mosquitoes from which we are looking for viruses.
Impact We have analysed a number of samples, this has led to more collaboration with other partners such as USA CDC and University of Glasgow. In the process of this work we have identified Le Dantec virus, only previously identified in two people in West Africa and in UK
Start Year 2015
 
Description Superinfection studies 
Organisation Johns Hopkins University
Department School of Medicine Johns Hopkins
Country United States 
Sector Academic/University 
PI Contribution Provision of samples Clinical and epidemiological data
Collaborator Contribution Training in neutralization and screening for neutralization
Impact Training of staff and generation of results
Start Year 2015
 
Description Superinfection studies 
Organisation National Institute of Virology Johannesburg
Country South Africa 
Sector Academic/University 
PI Contribution Provision of samples Clinical and epidemiological data
Collaborator Contribution Training in neutralization and screening for neutralization
Impact Training of staff and generation of results
Start Year 2015
 
Description University of Edinburgh Phylogenetics and Phylogeograghy of HIV 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of samples and sequences
Collaborator Contribution Training including PhD supervision, opportunities for attachments, transfer of sequence analysis capacity, contribution to publications
Impact Publications, Training and attachments
Start Year 2015
 
Description Use of HIV full length sequencing to characterise HIV epidemics and evaluate interventions 
Organisation University College London
Department UCL Genomics
Country United Kingdom 
Sector Academic/University 
PI Contribution We provide specimens including clinical and epidemiological data. We also participate in the analysis of data
Collaborator Contribution They provide funds, sequencing of the samples and training in the analyses of large sequence data
Impact Conference Abstracts, paper manuscripts, we have also started analysing of near full length sequencing of HIV sequences within our Uganda Medical Informatics Centre
Start Year 2014
 
Description Media interview of Medical Informatics 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I was interviews about our Medical Informatics Centre. There is interest in data analysis and how this can help other scientists and ministries. This media was organized to educate the public about our capacity and opportunities
Year(s) Of Engagement Activity 2017
 
Description Uganda Medical Informatics Centre, capacity 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was intended to present the capacity of our Medical Informatics Centre, in order to expand our collaborations
Year(s) Of Engagement Activity 2017