Overview (Content and Syllabus etc):
Seminar 1: Immunoglobulin Annotation Optimizing and Benchmarking and Novel Germline Allele Discovery in African Bovine Breeds Michael Kofia Landi1, 2, Jean-Baka Domelevo Entfellner4, Sonal Henson3 1Department of Biochemistry and Biotechnology, Pwani University, P.O Box 195-80108, Kilifi Kenya. 2International Center of Insect Physiology and Ecology, P.O. Box 300772-00100 Nairobi, Kenya. 3International Livestock Research Institute, PO Box 30709 Nairobi 00100 Kenya. 4Biosciences eastern and central Africa, ILRI, P.O. Box 30709 Nairobi 00100 Kenya. Abstract Antibodies are critical molecules of the adaptive immune response of vertebrates. For an animal to be able to neutralize all the pathogens it will encounter in its lifetime, the diversity of antibodies it will need to produce is enormous. Vertebrates achieve this through genetic recombination of immunoglobulin genes and post-somatic transcription mutations applied to so-called “germline” alleles. Bovine antibodies have distinct immunogenetics. Available annotation tools are human-centric, and therefore not optimized to annotate bovine immunoglobulin sequences. IMGT is a global database reference in immunogenetics and immunoinformatics. Some information from the IMGT database is not present for most species, as well as germline genes databases, which are not complete. Studies of germline alleles identification of cattle through novel allele discovery are necessary to complete germline gene databases of species. These discoveries are one step towards understanding the immunological complexity of these species. Using simulated bovine datasets, we benchmark the performance of three annotation tools IgBlast, IMGT/HighV-QUEST, and MiXCR based on mishit frequencies and distribution of these mishits. We evaluate two methods of germline allele discovery IgDiscover and TIgGER to determine their suitability for bovine germline allele discovery. IgM immunoglobulin sequences of three African bovine breeds, Ndama, Ankole, and Boran, were used in this analysis as well as Friesian cattle breed that was used as a control. We found that, for annotation of VH gene, IMGT/HighV-QUEST and IgBlast yielded a more accurate annotation with a 4% error rate, compared to MiXCR, which had a 13% error rate. MiXCR annotated JH genes with an error rate of 15% compared to IgBlast and IMGT/HighV-QUEST, which had an error rate of 40% and 43%, respectively. IgDiscover identified 18 novel alleles from Boran breed, six novel alleles from Ndama breed, and three novel alleles from Ankole breed. TIgGER, on the other hand, discovered seven novel alleles from Boran, 18 novel alleles from Ndama, and one novel allele from Ankole breed. This discovery of novel alleles shows that there is a need for further studies to be done in characterizing the immune system of African breeds. Using pairwise hamming distances of these novel alleles discovered we conclude that African novel germline alleles are more diverse compared to the Friesian novel germline alleles. H3ABioNet-Fogarty Collaborative Research Seminar Series The H3ABioNet-Fogarty Seminar coordinators and task force cordially invite you to join us for the next Fogarty Student Seminar in August 2020. Each Seminar will see two Fogarty students (MSc/Mphil/PhD) present a talk related to their ongoing projects. Seminar Format: A seminar talk will be provided by Michael Kofia Landi (Pwani University) and Mohamed MAIGA (USTTB). Each talk will be roughly 20 - 25 mins in length with around 10 to 15 minutes of Questions & Answer and discussion. Seminar Date: Tuesday, 25th August 2020 Seminar time: 9:30am EDT / 1:30pm UTC / 2:30pm WAT /2:30pm LT/ 3:30 pm CAT / 4:30pm EAT URL to join the seminar: https://zoom.us/j/98971424270 Previous H3ABioNet seminars are available on YouTube Seminar 2: Imidazolopiperazines Kill both Rings and Dormant Rings in Wild-Type and K13 Artemisinin-Resistant Plasmodium falciparum In Vitro Mohamed Maiga1 1Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), MRTC–DEAP–Faculty of Pharmacy, Bamako, Mali Abstract Artemisinin (ART) resistance has spread through Southeast Asia, posing a serious threat to the control and elimination of malaria. ART resistance has been associated with mutations in the Plasmodium falciparum kelch-13 (Pfk13) propeller domain. Phenotypically, ART resistance is defined as delayed parasite clearance in patients due to the reduced susceptibility of early ring-stage parasites to the active metabolite of ART dihydroartemisinin (DHA). Early rings can enter a state of quiescence upon DHA exposure and resume growth in its absence. These quiescent rings are referred to as dormant rings or DHA-pretreated rings (here called dormant rings). The imidazolopiperazines (IPZ) are a novel class of antimalarial drugs that have demonstrated efficacy in early clinical trials. Here, we characterized the stage of action of the IPZ GNF179 and evaluated its activity against rings and dormant rings in wild-type and ART-resistant parasites. Unlike DHA, GNF179 does not induce dormancy. We show that GNF179 is more rapidly cidal against schizonts than against ring and trophozoite stages. However, with 12 h of exposure, the compound effectively kills rings and dormant rings of both susceptible and ART-resistant parasites within 72 h. We further demonstrate that in combination with ART, GNF179 effectively prevents recrudescence of dormant rings, including those bearing pfk13 propeller mutations.
Michael Kofia Landi is an EANBiT scholar pursuing an MSc in Bioinformatics. He is a graduate at Pwani University holding a BSc. Biochemistry. He is currently undertaking his research project at the BecA-ILRI hub aimed at discovering novel germline alleles in African bovine breeds. He is a co-founder of Bioinformatics hub of Kenya, an initiative that promotes training, networking and collaboration. He is an Open Life Science (OLS) graduate. He has developed a keen interest in Immunoinformatics through his master project and developing workflow management systems to enhance reproducible and scalable data analysis.
Mohamed MAIGA is a Malian student at the end of his master's degree in bioinformatics at the African Centre of Excellence of the University of Science, Technology and Technology of Bamako (USTTB). He is currently working on his thesis project, which consists in deciphering the mechanism of action of GNF179 (antimalarial drug) on malaria parasites with a transcriptomic study. My experiences acquired during my training in Biological Sciences and in the teaching of science in high schools have developed in me a great interest in scientific research. It is for this reason I was motivated after my teaching biology in the basic schools of northern Mali (Gao community) from 2009-2015, I took an entrance exam for the Faculty of Science and Technology in Bamako to obtain a degree in Biochemistry and Microbiology. During my degree, I did internship in the Laboratory of Molecular Biology and Microbial Biotechnology Research Laboratory (LABOREM) within the Faculty of Science and Technology (FST). I participated in a project with Professor Amadou A Diallo (Director of Laborem) which consists of isolating and carrying out metagenomics of Actinomycetes from the soil of northern Mali (Saharan zone) to search for genes of interest that could improve conditions between the plant and the soil. In recognition of my efforts in Bachelor's degree, (valedictorian) I received assistance (tuition fees) from the NIH to do a Master's degree in Bioinformatics at the African Center of Excellence (ACE) in Bioinformatics in Bamako, Mali. During the period of my course work in the first semester, I did an internship in a UCRC (University Clinical Research Center) research laboratory at point G in Bamako under the supervision of Dr Almoustapha Maiga (Director General of the Gabriel Toure Hospital Laboratory), there I worked on the quantification of viral loads of HIV-positive patients to see and understand patients who develop a form of anti-retrovirus resistance in order to subject them to more specific treatment.
Instructions for Pre-Webinar Exercises:
Webinar organisers.Organizing body contact details:
Webinar Organisers/Organizing Body:
Name of the Speaker:
Michael Kofia Landi
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Host H3Africa Project/Organizations/H3Africa Working Group:
H3Africa Administrative Coordinating Centre: Enabling and Supporting Genomics and Health Research Capacity Building in Africa
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Dates of Event:
Tuesday, August 25, 2020 - 15:30 to 16:30