Improved infectious diseases research and surveillance in Ethiopia through capacity building in bioinformatics and sequencing

June - July 2018

From June 18th to July 6th, the TORCH consortium organized its first Ethiopian VLIR project, together with Prof. Gemeda Abebe (Jimma University) and Dr. Conor Meehan (Institute of Tropical Medicine). In the months leading up to the training, 5 young scientists were selected from a pool of applications by the TORCH consortium organizers. These scientists included:

• Muluwork Getahun: National Tuberculosis Reference Laboratory (Addis Ababa)

• Mulualem Tadesse: Jimma University, PhD at Institute of Tropical Medicine

• Shewki Moga: National Tuberculosis Reference Laboratory (Addis Ababa)

• Solomon Ali: Jimma University

• Adane worku: Addis Ababa University

One additional trainee was recommended by our collaborators at the Institute for Tropical Medicine. Mebrat Ejo, who is doing a PhD at the Institute of Tropical Medicine, joined the group, meaning that this training featured six trainees instead of five.

Whole Genome Sequencing
During the first week of the training, the Ethiopian trainees were exposed to whole genome sequencing through both theoretical an practical sessions. An extraction protocol was executed on cultures of M. smegmatis, cultured at the Institute of Tropical Medicine. Sequencing libraries were prepared and from the extracted DNA and were finally sequenced using an Illumina Miseq platform. Additionally, Peter Van Hauwe, Illumina representative, gave an extended talk about the Illumina company, the products (sequencing kits and platforms) and support. Illumina kindly provided us the sequencing kit that was used for this training. Use this link for more information on Illumina sequencing kits. Finally, Pauline Lempens, PhD student at the Institute for Tropical Medicine, held a session on packaging and shipping high quality DNA samples, specifically from Ethiopia.

Bioinformatics
In the second week, the trainees were given a crash course on the bioinformatics side of whole genome sequencing. After giving a short but comprehensive Unix tutorial written by Dr. Conor Meehan, the trainees were taught how to use the open source MTBSeq pipeline, published by Stefan Niemann's group (Borstel, Germany). Because the trainees had no prior experience with the command line, it was made sure that all of them understood the concepts of the modular MTBSeq pipeline and how they could invoke the MTBSeq command. In the last week of the training, Dr. Tim Heupink held a session on phylogeny and TB transmission and how sequencing data can be analysed by using the Illumina Basespace platform.

Public Health
Under guidance of Prof. Annelies Van Rie, Dr. Conor Meehan and Elise De Vos, the trainees were requested to develop a research project that encompassed both tuberculosis and whole genome sequencing. The trainees were given the assignment to work on this project as much as possible, and to formally present their work on the final day of the training. To support the development of their projects, during the three week course, several theoretical sessions were held on public health and project management topics such as formulating an objective and specific aims, study design, study procedures, ethics, timeline, budget, feasability and risk management. On the last day, all the trainees succesfully presented their research projects:

• Muluwork Getahun: “Compensatory mutation and relative fitness cost of the two most frequent MDR TB stains in Ethiopia”

• Mulualem Tadesse: "Mycobacterium tuberculosis transmission dynamics among University students in Ethiopia: A whole genome sequencing  study"

• Shewki Moga: “Genetic diversity of isoniazid resistant rifampicin susceptible Mycobacterium tuberculosis in Ethiopia”

• Solomon Ali: “Impact of MTB genetic variants on the extent of lung impairment”

• Adane Worku: “Genotypic characterization of Mycobacterium tuberculosis and Mycobacterium bovis in Human and Animal by Whole Genome Sequencing”

• Mebrat Ejo: "Characterization of drug resistance patterns and genetic factors associated with slow growth of Mycobacterium tuberculosis lineage 7"

Wrap up & future perspectives
One of the main goals of this VLIR-UOS training was that the trainees would develop their own projects about tuberculosis and whole genome sequencing and that we would create a peer review system among them. Based on the enthusiastic and collaborative training sessions and the formal presentations on the final day, we can proudly conclude that we managed to meet this objective. 6 trainees arrived in Antwerp with limited prior knowledge on DNA sequencing and no prior knowledge on Bioinformatics. 3 weeks later, 6 trainees left with interesting research projects that all implement whole genome sequencing to answer some very specifc and critical research questions.
This theoretical and practical training was only the beginning of the project, as the TORCH consortium will now focus on further mentoring of the trainees, to ensure that they manage to finish their research proposals and obtain ethical approval. Several calls will be held to closely follow up the progress made on each project in addition to regular journal clubs. Once ethical approval is obtained and the pilot studies can begin, the South African members of the consortium will ensure that the lab work will be conducted in a best practice manner, while the Belgian consortium members and the collaborators at the Institute for Tropical Medicine will provide assistance with the data analysis. More updates will follow.

Back