Research Article: The Collaborative African Genomics Network (CAfGEN): Applying Genomic technologies to probe host factors important to the progression of HIV and HIV-tuberculosis infection in sub-Saharan Africa

Date Published: June 21, 2018

Publisher: F1000 Research Limited

Author(s): Gerald Mboowa, Savannah Mwesigwa, Eric Katagirya, Gaone Retshabile, Busisiwe C. Mlotshwa, Lesedi Williams, Adeodata Kekitiinwa, David Kateete, Eddie Wampande, Misaki Wayengera, Betty Nsangi Kintu, Grace P. Kisitu, Samuel Kyobe, Chester W. Brown, Neil A. Hanchard, Graeme Mardon, Moses Joloba, Gabriel Anabwani, Ed Pettitt, Masego Tsimako-Johnstone, Ishmael Kasvosve, Koketso Maplanka, Sununguko W. Mpoloka, Makhosazana Hlatshwayo, Mogomotsi Matshaba.

http://doi.org/10.12688/aasopenres.12832.2

Abstract

Background: Here, we describe how the Collaborative African Genomics Network (
CAfGEN) of the Human Heredity and Health in Africa (H3Africa) consortium is using genomics to probe host genetic factors important to the progression of HIV and HIV-tuberculosis (TB) coinfection in sub-Saharan Africa.   The H3Africa was conceived to facilitate the application of genomics technologies to improve health across Africa..         

Partial Text

In 2011, a group of scientists came together and conceived the white paper “
Harnessing Genomic Technologies Toward Improving Health in Africa: Opportunities and Challenges”
1. Currently, much research in Africa is funded through foreign granting mechanisms
2 and many PhD level scientists in Africa have received their training at foreign institutions
3. Unfortunately, scientists often leave for training and do not return to Africa because of limited opportunities on the continent
4. The Human Heredity and Health in Africa consortium (H3Africa ) was initiated, in part, to reverse this ‘brain drain’ and has already made substantial strides towards this goal and the Collaborative African Genomics Network (
CAfGEN) is an H3Africa collaborative centre.

After the H3Africa white paper, a request for application (RFA) was released and collaborative centers applied for funding in health-related areas of research (see
NIH H3Africa grant page), including ;

CAfGEN seeks “to create a collaborative, multi-disciplinary, multi-institutional, inter- and intra-country network of African scientists, clinicians, and researchers using genomics approaches to study gene/environment interactions for HIV/AIDS, its co-morbidities, and other diseases among diverse paediatric African populations.” To meet the attendant challenges of accomplishing this mission, a highly collaborative, synergistic, network of institutions has been assembled.

Disproportionately few advanced genetic and genomic studies have involved the indigenous peoples of Africa, and even fewer have included African paediatric populations
19–
21. Yet, paradoxically, these populations collectively carry a large proportion of the human disease burden that results in significant mortality and morbidity. HIV/AIDS and TB – HIV’s most frequent co-morbidity – exemplify this scientific disparity; together, HIV and HIV-TB result in more than 500,000 new childhood cases every year (see
UN report on combatting HIV/AIDS, Malaria and Other Diseases). Studies of host genetic factors underlying Long-Term Non-Progressors (LTNPs) of HIV infection have led to new therapies through the identification of loci that are important to
in vivo control of virus pathogenicity
22. Similarly, a detailed understanding of the temporal
in vivo host molecular events occurring in the progression to active TB disease in the face of HIV co-infection, could significantly impact development of effective therapeutic strategies. Although genomic approaches have been used to identify host response pathways that are important to TB-disease progression, almost all of these studies were undertaken in non-African, adult populations. HIV-infected Africans and particularly children – who have a different route of acquisition, clinical course, and pathophysiology from their adult counterparts – have not been included, although they potentially have more to ultimately contribute and gain from any therapeutic advances.
CAfGEN envisaged a project that encompassed 5 inter-related aims:

Following the completion of more than two years of didactic training in genomics and bioinformatics at BCM,
CAfGEN trainees are currently analyzing the genomic data at their respective institutions utilizing local computing resources made possible by
CAfGEN funding while they continue to receive both mentorship and supervision from their BCM mentors.

The
CAfGEN project has enabled six PhD students to successfully complete their intensive genomics training at BCM. They are all being supported to complete their PhDs at their home institutions. The project allowed the purchase of both an ABI 3500 Capillary sequencer (Life Technologies, CA) and a MiSeq System (Illumina, San Diego, CA) for the University of Botswana and Makerere University, respectively. The acquisition of these instruments has already spurred new opportunities for genomics training and research at these institutions. In particular, the ”
Introduction to Bioinformatics and Next Generation Sequencing Techniques” workshop was funded by the World Bank through the African Higher Education Centres of Excellence Project (MAPRONANO ACE II) and attended by 52 researchers from Rwanda, Tanzania, Zambia, Ethiopia, Kenya, Malawi, and Uganda, the
Bioinformatics RNA sequence data analysis workshop was funded by the Alliance for Global Health Science also attended by 19 participants from Uganda and Zimbabwe and one-year training program funded through the University of Georgia’s “Computational and Molecular Epidemiology in TB and HIV in Uganda”. This mentorship program offers a unique training arrangement to students who have special interest in genomics and bioinformatics to attend weekly tutorials and practical sessions offered by faculty genomics mentors throughout the year. The program is currently training four students at Makerere University (D43TW010045-03).
CAfGEN trainees are at the centre of these trainings and workshops.

The opportunity offered by studying HIV and HIV-TB coinfection in children at the COEs and integrated genomics training in both Botswana and Uganda has permitted us to pioneer a new method of undertaking genomics and biomedical research in Africa whilst building sustainable expertise and infrastructure. This innovative approach has registered significant gains in achieving the goal of H3Africa. Furthermore, we have successfully ensured that the acquired genomics expertise is transferred to Africa as trainees returned to their home countries to take faculty positions, transfer skills and participate in genomics-driven research pertinent to African populations with a goal of improving health.

All data underlying the results are available as part of the article and no additional source data are required.

 

Source:

http://doi.org/10.12688/aasopenres.12832.2

 

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