CONTENTS

13TH H3AFRICA FELLOWS’ AGENDA ...... 2

ABSTRACTS...... 7

BIOGRAPHIES ...... 24

FELLOWS ...... 24

TRAINERS ...... 30

ORGANIZING TEAM ...... 33

EMERGENCY NUMBERS ...... 34

SITE MAP ...... 35

NOTES ...... 36

1 | P a g e

13TH H3AFRICA FELLOWS’ AGENDA H3Africa Fellows Professional Development Workshop 7 -11 April 2019 Institute Pasteur de Tunis & Laico Hotel Tunis Tunisia DAY 1: 7 APRIL SCIENTIFIC WRITING AND PROMOTING RESEARCH VISIBILITY Institute Pasteur de Tunis, Tunisia Facilitators: Dr. Maria Kabbage &Hamza Dalleli 8:00 Bus departs Laico Hotel 8:30 – 8:45 Registration 8:45 – 9:00 Welcoming address 09:00 – 10:45 Dr. Sadri Znaidi How to write a research paper and get it published? 10:45 – 11:00 MORNING TEA/COFFEE BREAK 11:00 — 13:00 Dr. Sadri Znaidi How to write a research paper and get it published? 13:00– 14:00 LUNCH Dr Amel Ghouila How to increase visibility of research?, popular articles 14:00 – 15:00 Dr Rolanda Julius and social media platforms best practises Dr Amel Ghouila Applying for coveted positions or fellowships? A few 15:00 — 16:00 Mr Paballo Chauke tips for successful applications 16:00 — 16:15 AFTERNOON TEA/COFFEE BREAK 16:15 – 16:30 Closing and return to Laico Hotel TBA FELLOWS’ DINNER (Venue TBA) DAY 2: 8 APRIL GRANT WRITING Carthage, Laico Hotel Tunis National Institutes of Health African Academy of 08:00 – 12:30 Institutional overviews, lesson learned. Sciences Wellcome Trust H3Africa PI’s 12:30 – 12:50 LUNCH 12:50 – 13:30 Ambroise Wonkam Lessons learned Grant Writing Break-Out Session Escale, Laico Hotel Tunis Facilitators: Dr. Maria Kabbage, Maroua Boujemaa & Pr. Sonia Abdelhak Pr. Ikram Guizani 13:30 – 15:15 Applying for Career development grants Dr. Rym Kefi Pr. Ikram Guizani 15:15 — 16:15 Applying for Career development grants Dr. Rym Kefi 16:15 – 16:30 TEA/COFFEE AVAILABLE Pr. Ikram Guizani 16:30 – 17:00 Applying for Career development grants Dr. Rym Kefi Opening of the 13th Meeting of the H3Africa Consortium 19:00 – Cocktail Reception DAY 3: 9 APRIL PI & FELLOW PRESENTATIONS Carthage, Laico Hotel Tunis 07:00 – 08:00 Registration Anita Ghansah & Paulina Tindana 08:00 – 09:30 Joseph Ochieng PI presentations Rufus Olusola Akinyemi Jantina de Vries

2 | P a g e

TEA/COFFEE BREAK/ POSTER SESSION Dhyafa Foyer The use of H3ABioNet node accreditation exercises in Melek Chaouch (Fellow) capacity building in Tunisia Pierre-Jean Laclide Benchmarking of RNAseq data analysis 09:30 – 09:50 (Fellow) Tunisians Youth Literacy to Seasonal Influenza: Foued Maaoui (Fellow) Antibiotics Versus Empathy Chandré Oosterwyk Investigating the microbiome profile in sickle cell (Fellow) disease patients in Cape Town PI & FELLOW PRESENTATIONS Infectious Disease Chair: Ayoade Oduola

Project: Genomic Characterization and Surveillance of Microbial Threats in West Africa 09:50 – 10:20 Christian Happi (PI) 16 TBA minutes Q&A: 2 minutes Fehintola Ajogbasile (Fellow) 10 minutes Identification and Characterization of Yellow Fever Q&A: 2 minutes Virus (YFV) in VHF Suspected Samples by Genomics Deep Sequencing in Nigeria Project: TrypanoGEN +: The Genetic Determinants of Two Neglected Tropical 10:20 – 10:50 Diseases Enock Matovu TBA 25 minutes Q&A: 5 minutes Project: Center for Research on the Respiratory Microbiota of African Children (ReMAC) TBA 10:50 – 11:20 Mark Nicol (PI) 16 minutes Q&A: 2 minutes Prevalence and characterization of haemophilus Fadheela Patel (Fellow) influenzae in the nasopharynx of young children, South 10 minutes Q&A: 2 Africa minutes Project: SickleGenAfrica:Sickle Cell Disease Genomics 11:20 — 11:50 Network of Africa Solomon Ofori-Acquah 25 minutes Q&A: 5 TBA minutes 11:50 – 12:50 LUNCH (El Maeeda) FELLOW PRESENTATIONS Chair: Melek Chaouch

3 | P a g e

Jean Tristan Brandenburg Prevalence, risk factors and genetic associations for 12:50 – 13:02 (PI: Ramsay) chronic kidney disease related variables in four sub- 10 minutes Q&A: 2 Saharan African countries: an AWI-Gen sub-study mins. Careen Naitore The developmentally dynamic microRNA transcriptome (PI: Masiga) 13:02 – 13:14 of Glossina pallidipes tsetse flies, vectors of sleeping 10 minutes Q&A: 2 sickness and animal trypanosomiasis minutes Monica Mbabazi (PI: Kateete) Sputum microbiome composition through treatment of 13:14 – 13:26 10 minutes Q&A: 2 TB patients in an endemic setting minutes Medhat Radi Bioinformatics analysis of nicotinic acetylcholine (PI: Mulder, Alzohairy) 13:26 — 13:38 receptor subunit α 8 (nAchra8) protein evolution in 10 minutes Q&A: 2 different higher and lower organisms minutes Noluthando Manyisa Whole Exome Sequencing reveals differential (PI: Wonkam) 13:38 — 13:50 frequencies in ancestral alleles in Hearing Impairment 10 minutes Q&A: 2 genes among patients compared controls in Cameroon minutes TEA/COFFEE BREAK/ POSTER SESSION Dhyafa Foyer BRCA1-c.211dupA a recent founder mutation in Najah Mighri (Fellow) Tunisian breast cancer patients: implication on clinical management and early disease detection Pleiotropic effects of molecular and cellular factors in 13:50 — 14:10 Imen Moumni (Fellow) sickle cell anemia Multidisciplinary investigation of rare genetic diseases Lilia Romdhane (Fellow) in Tunisia Hydroxyurea-induced miRNA expression in Sickle Cell Khutala Mnika (Fellow) Disease patients in Africa PI & FELLOW PRESENTATIONS Chair: Rex Chisholm Alash’le Abimiku 14:10 — 16:40 Clement Adebamowo PI presentations Zane Lombard Project: Immunoglobulin gene diversity in an African

population and impact

on antibody function in

HIV infection

Simone Richardson

16:40 — 17:10 16 minutes Q&A 2

minutes

Simone Richardson Allelic variation in African immunoglobulin genes (Fellow) impacts on antibody function in HIV infection (PI: Lynn Morris) 10 minutes Q&A: 2 minutes 17:10 — 17:40 Dan Stein PI presentation DINNER (The Bridge Restaurant) DAY 4: 10 APRIL PI & FELLOW PRESENTATIONS

4 | P a g e

Carthage, Laico Hotel Tunis 8:00 — 8:50 Samantha Nicolson Keynote address PI & FELLOW PRESENTIONS Chair: Phillip Awadalla Nicola Mulder 8:50 — 9:40 Nicola Mulder PI presentations Daudi Jjingo Maroua Boujemaa (PI: Alia Benkhala) Contribution of Germline Copy Number Variations to 9:40 — 9:52 10 minutes Q&A: 2 hereditary breast cancer in Tunisian Population minutes 9:52 — 10:10 Rolanda Julius Presentation TEA/COFFEE BREAK/ POSTER SESSION Dhyafa Foyer Effect of Vitamin D Binding Protein Gene Polymorphism Ester Acen (Fellow) and Vitamin D Bioavailability on Cathelicidin Expression in Tuberculosis Infection and Disease The importance of considering natural isotopes in Sara El Jadid (Fellow) improving protein identification accuracy 10:10 — 11:00 Metagenomic analysis of blood samples obtained from Judith Oguzie (Fellow) febrile patients in Nigeria H3Africa/GSK ADME: High throughput analysis of ADME Houcemeddine Othman pharmacogenomic variants at genomic and protein (Fellow) levels in African populations MultiOmeSEQ: A suite of tools for integrated analysis of Alfred Ssekagiri (Fellow) multi-level omics datasets OUTREACH & FELLOWS PRESENTATIONS Chair: Francine Ntoumi Science Shop as a tool for participatory research. The Hichem Ben Hassine 11:00 — 11:15 experience of Institut Pasteur de Tunis in the context of

the H2020 InSPIRES Q&A 2 min Social and scientific engagement of young Tunisian 11:15 — 11:30 Maria Kabbage researchers: the experience of AJC-IPT Q&A 2 min Mariem Hanachi Genomic characteristics of Invasive Streptococcus 11:30 — 11:42 (PI: Aliah Benkahla) pneumoniae serotype 1 in New Caledonia, a region in 10 min Q&A 2 min Oceania with a high incidence of serotype 1 outbreaks Hamza Dalleli (PI: Alia Benkhala) Targeted Next Generation Sequencing applied for the 11:42 — 11:54 10 minutes Q&A: 2 molecular characterization of MODY patients in Tunisia minutes 11:54 — 12:10 Prof Ferrand Presentation 12:10 —12:25 Dr Jennifer Troyer Presentation 12:25—13:10 Drama of DNA Production 13:10 — 14:00 LUNCH FELLOWS’ SPEED PRESENTATIONS Cyrene, Laico Hotel Tunis Chair: Dr Maria Kabbage Facilitators: Dr. Najla Kharrat, Meriem Fassatoui, Cyrine Bouabid, & Verena Ras Investigating Genetic Markers of Autosomal Recessive 14:05 — 14:08 Elvis Twumasi Aboagye Non-Syndromic Hearing Impairment in Ghana Design and validation of Human Papillomavirus 14:08— 14: 11 Monia Ardhaoui genotyping by next generation sequencing technology

5 | P a g e

A common molecular signature of patients with sickle 14:11 — 14:14 Cherif Ben Hamda cell disease revealed by microarray meta-analysis and a genome-wide association study Transcriptional Signatures of Active TB Disease in HIV 14:14 — 14:17 Eric Katagirya co-infected Children in Uganda and Botswana Homology modeling and docking of AahII-Nanobody 14:17 — 14:20 Ayoub Ksouri complexes reveal the epitope binding site on AahII scorpion toxin Whole-exome sequencing of sickle cell disease patients 14:20 — 14:23 Savannah Mwesigwa with hyperhemolysis syndrome suggests a role for rare variation in disease predisposition Abnormal monocyte phenotypes, immune activation, 14:23 — 14:26 Rose Nabatanzi and inflammation persist despite long-term antiretroviral therapy in an African cohort PRIMO: modeling protein complexes and building 14:26 — 14:29 Margaret Nabatanzi biological assemblies Evaluation of Microorganisms Population from Cattle Chukwuemeka 14:29 — 14:32 Egret Droppings in a Residential Area in Ogun State, Nwankwo Nigeria. Minimum Information Required Research Reporting 14:32 — 14:35 Lyndon Zass Guidelines - Case Studies from H3Africa 14:35 — 14:45 Questions 14:45 — 15:00 Consolidate scores Nick Tiffin 15:00 — 15:30 Laura Povlich Feedback session for all presentations Sonia Abdelhak TEA/COFFEE available 16:00 — 18:00 WG sessions DINNER

H3Africa Fellows Prize Giving DAY 5: 11 APRIL LEADERSHIP SKILLS Escale, Laico Hotel Tunis Facilitators: Dr. Melek Chaouch & Maroua Boujemaa Paballo Chauke 08:00 — 8:30 Yosr Hamdi Recap and summary Rolanda Julius Ahmed Rebai 08:30 — 10:00 Leadership in scientific research Sonia Abdelhak 10:00 — 10:15 TEA/COFFEE available Ahmed Rebai 10:15 — 12:00 Leadership in scientific research Sonia Abdelhak

6 | P a g e

ABSTRACTS

Investigating Genetic Markers of Autosomal Recessive Non-Syndromic Hearing Impairment in Ghana Elvis Twumasi Aboagye (1), Ambroise Wonkam (2), Gordon Awandare (3) (1) West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, P.O. Box LG 25, Legon (2) Division of Human Genetics Level 3, Wernher and Beit North, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town (3) West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, P.O. Box LG 25, Legon INTRODUCTION: Hearing Impairment (HI) affects 5% of the world population (466 million), making it the most prevalent sensory human defect. Variations in gap junction beta-2 protein (GJB2) and gap junction beta-6 protein (GJB6) have been implicated in 50% of autosomal recessive non-syndromic hearing impairment cases in the most population. Although GJB2, GJB6, and GJA1 have been investigated in sub-Saharan Africa, the prevalence of implicated causal variants is insignificant. The causative HI gene mutations identified in developed settings are well documented with the challenge of phenotypic-genotypic correlations for translational benefits. However, published data on the genetic etiology of HI in Africa are limited, although the reported causative genes may explain only 4.1% of autosomal recessive non-syndromic hearing impairment (ARNSHI) in African-Americans. OBJECTIVES: This study seeks to elucidate specific genetic markers (gene mutations, copy number variations, and epigenetic marks) associated with ARNSHI in Ghana. We will also validate the genotypic-phenotypic correlations of markers identified, and develop a molecular diagnostic tool to complement newborn screening. METHODOLOGY: This study will recruit familial and isolated ARNSHI probands across Ghana, from the school for the deaf. Pedigree analysis and molecular investigations will be used to elucidate carrier frequencies of associated gene variants and determine expressivity levels and percentage of penetrance, as well as the pattern of segregation. First-degree siblings and parents of probands and ethnic group and age match controls recruited as comparisons for the study. Next-generation whole Exome sequencing (WES), whole genome sequencing (WGS) and Global DNA methylation assay, will be performed to identify ARNSHI implicated markers. Tissue-specific expression experimentation using human cell-lines based on genes identified will be utilized for the functional analysis. The phenotypic-genotypic correlation of ANSHI gene variants validation will be carried out following the American College of Medical Genetics and Genomics guidelines on interpretation of the pathogenicity of genetic variants. NEXT STEPS: Beyond these objectives, we look forward to using animal models to investigate and determine an effective management strategy and treatment intervention that targets the implicated marker action. Community engagement studies to sensitize families on hereditary of hearing impairment to promote newborn genetic screening.

Effect of Vitamin D Binding Protein Gene Polymorphism and Vitamin D Bioavailability on Cathelicidin Expression in Tuberculosis Infection and Disease Acen Lilian Ester, William Worodria, Irene Andia, David P Kateete, Moses Joloba INTRODUCTION: Genetic polymorphisms of the Gc gene are presumed to cause vitamin D deficiency by modifying the affinity of vitamin D metabolites leading to variable vitamin D circulatory levels. We hypothesize that cathelicidin (LL-37) may be a potential biomarker of TB infection and disease and bioavailable vitamin D levels will be a better determinant of cathelicidin expression. Individuals with vitamin D deficiency are more susceptible to TB and patients with TB have lower serum vitamin D levels than contacts from the same ethnic location. Through Toll-like receptors (TLRs) (LL-37) antimicrobial peptide is involved in innate immunity by direct killing of MTB in a vitamin D dependant manner.The free hormone hypothesis reports that the free and bioavailable vitamin D fraction is biologically active. OBJECTIVE: This study will determine the effect of the DBP genetic polymorphism and bioavailable vitamin D on the expression of cathelicidin antimicrobial peptide as a probable biomarker of TB infection and disease. METHODS: An analytical cross-sectional study of 252 participants will be carried out among 84 active TB patients, 84 latent TB individuals and 84 non TB. Consecutive sampling will be sued for active TB recruitment at Mulago Hospital. Samples of latent TB individuals and non TB controls from the Kampala TB cohort (KTB) study stored at the Uganda Virus Research Institute (UVRI) repository will be retrieved for analysis too. Two polymorphisms rs4588 and rs7041 will be genotyped by PCR- Direct sequencing method using real-time PCR and Sanger sequencing. Free serum 25(OH) D and LL-37 will be measured among 102 individuals in the three groups of 34 each by competitive ELISA kits and Sandwich enzyme immunoassay ELISA kits respectively. Data will be analyzed using STATA software version 12.0. The frequency distribution of the DBP gene polymorphism will be compared using frequencies and percentages. Bioinformatics tools will be used for polymorphism identification. Vitamin D and Serum LL-37

7 | P a g e concentration will be compared. DBP gene, vitamin D and LL-37 concentration will be compared for any association using linear regression and multivariate analysis with other variables. Association between DBP gene, vitamin D and will be assessed. The levels of bioavailable 25(OH) D will be compared with LL-37 levels and cytokines among cases and controls using means and standard deviations. NEXT STEPS: Frequency distribution of DBP and association of vitamin D status and LL-37 concentration will be known among the three groups. The Prediction will be done for LL-37 as a potential biomarker compared to tuberculin skin test (TST) and QuantiFERON TB Gold (QFT) for monitoring progression to disease.

Identification and Characterization of Yellow Fever Virus (YFV) in VHF Suspected Samples by Genomics Deep Sequencing in Nigeria. F.V. Ajogbasile (1,2)*, J.U. Oguzie (1,2)*, P.E. Oluniyi (1,2)*, P.E. Eromon (2), J.N. Uwanibe (1,2), K.J. Siddle (3), S.B. Mehta (3,4), I. Odia (5), O.A. Folarin (1,2), P.C. Sabeti (3), C.T. Happi (1,2) (1) Department of Biological Sciences, Redeemers University, Ede, Osun State Nigeria (2) African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemers University, Ede, Osun State Nigeria (3) Broad Institute and Harvard University, Boston, USA (4) Beth Israel Deaconess Medical Center, Boston, USA (5) Institute of Lassa fever Research and Control, Irrua Specialist Teaching Hospital (ISTH), Edo State, Nigeria INTRODUCTION: Viral Hemorrhagic Fevers (VHFs) are febrile illnesses caused by several distinct families of RNA viruses, their clinical symptoms are accompanied by fever and bleeding making it difficult to diagnose and distinguish them. In November 2018, there was an outbreak of a VHF of unknown origin in the Edo State of Nigeria. Diagnosis of Yellow fever virus (YFV) was difficult because it is a region endemic for Lassa fever. OBJECTIVE: To use real-time deep sequencing and molecular techniques to identify and characterize the etiology of a VHF outbreak in Nigeria in order to inform the management and control of the outbreak. METHODOLOGY: Real-time massively parallel sequencing analysis was carried out on 14 plasma samples obtained from febrile patients in ISTH with unknown etiologies at ACEGID. RNA was extracted from samples using the QiAmp viral RNA mini kit (Qiagen). cDNA libraries were prepared using the Nextera XT kit for sequencing on Illumina MiSeq platform. Sequencing data were analyzed using publicly available software ‘viral-ngs’ (version 1.21.2) and KrakenHLL (version 0.4.8). RT-qPCR was used to further confirm YFV in the plasma samples. PRELIMINARY RESULTS: The samples tested negative for Lassa fever, malaria, and typhoid fever prior to arrival. YFV was detected in 9 (62.3%) of the 14 samples by sequencing and qRT-PCR. However, YFV genomes were successfully assembled in 4 (44.4%) of the 9 samples confirmed for the presence of YFV. Phylogenetic analysis of approximately 680bp of the prM/E region of the viral genome revealed that the 2018 YFV sequences clustered in a separate clade sharing 99.4% pairwise identity with sequences from the nearest clade of YFV obtained from other West African countries. In contrast, these 2018 Nigerian YFV sequences shared 89.8% pairwise identity with earlier Nigerian samples ranging from 1946-1991, implying that this 2018 YFV cluster is genetically distinct from previous sequences reported in the country. Our data is suggestive that 2018 YFV outbreak in Edo State, Nigeria might have been from an imported source. NEXT STEPS: Efforts are ongoing to perform deep sequencing on more YFV suspected samples for a better understanding of the viral diversity and evolution in Nigeria.

Design and validation of Human Papillomavirus genotyping by next generation sequencing technology Ardhaoui Monia (1,2), Ennaifer Emna (1.2), De Matos Salim Anna Christina (3), Laasili Thalja (1.2), Marcom Gomez Flávio (3), Dultra Juliane (3),Volpini Angela, Oliviera Guilherme (3), Boubaker Med Samir (2), Guizani Ikram (2) (1) Department of Molecular Epidemiology of infectious diseases, Institut Pasteur de Tunis, Tunis, Tunisia, (2) Department of Human and Experimental Pathology, Institut Pasteur de Tunis, Tunis, Tunisia, (3) Genomics and Computational Biology Group, Fiocruz - Research Center Renê Rachou, Belo Horizonte, Minas Gerai, Brazil, BACKGROUND: The most used methodologies for Human papillomavirus (HPV) genotyping are based on hybridization methods. However, these methods are limited to a restricted number of HPV types and to the lack of specificity and sensitivity for same types. Recently, Next-Generation sequencing (NGS) technology has been efficiently used also for HPV genotyping, this methodology is based on massive sequencing of HPV fragments and is expected to be highly specific and sensitive. Thus, our objective was to develop an HPV typing method based on single-end Miseq NGS of HPV L1 amplicons generated with PYGMY09/11 and GP5+/GP6+ primers. In order to establish this method and to test its sensitivity notably in case of multiple HPV infection, we used the 43 WHO HPV

8 | P a g e

LabNet 2014 global proficiency test panel, made of complete genomes of HPV cloned into plasmid vectors and 10 clinical control samples. Therefore, we established a bioinformatic pipeline for HPV types identification and applied it to the sequences generated during the multiplexed runs. RESULTS: The NGS method allowed us to correctly identify all HPV types, in either single or multiple infections at a 1% frequency and with a sensitivity of 50 genome equivalents/µl, as demonstrated by testing WHO LabNet proficiency test panel. In addition, all viruses were correctly identified both in single and in multiple infections for the 10 cervical clinical samples. CONCLUSION: An HPV typing method based on single-end Miseq sequencing was developed. This technology was sensitive and precise for HPV genotyping in both single and multiple infections. It could detect a broad spectrum of HPV types and might potentially lead to identify new HPV types

Contribution of Germline Copy Number Variations to hereditary breast cancer in Tunisian Population Maroua Boujemaa (1), Yosr Hamdi(1), Hamza Dallali(1), Najah Mighri(1), Soumaya Labidi(1,2), Nesrine Mejri(1,2), Olfa Jaidane(3), Houda El Benna(2), Khaled Rahal(3), Sonia Ben Nasr(4), Abderazzek Haddaoui(4), Ridha Mrad(5), Hamouda Boussen(1,2), Mohamed Samir Boubaker(1) , Sonia Abdelhak(1), On Behalf of the PEC Consortium2 (1) University of Tunis El Manar, Institut Pasteur de Tunis, LR16IPT05 Laboratory of Biomedical Genomics and Oncogenetics,1002, Tunis, Tunisia (2) Department of Medical Oncology, Abderrahman Mami Hospital, Tunis, Tunisia (3) Salah Azaiez institute of cancer, Boulevard of 9-April 1938 1006 Tunis, Tunisia (4) Medical Oncology Service, Military Hospital of instruction of Tunis, Mont Fleury-1008 Tunis, Tunisia (5) Department of Human Genetics, Charles Nicolle Hospital, Tunis, Tunisia

Background: Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, only the known 50% of the breast cancer genetic component is explained by known genetic risk factors. Therefore, the basis for a significant fraction of genetic predisposition in familial breast cancer remains unsolved. Copy number variants (CNVs) might contribute to disease susceptibility in these unsolved cases. Methods: Nine breast cancer patients with strong family history as well as 10 healthy individuals were investigated by Whole Exome Sequencing. CNVs were called using ExomeDepth R package and investigated by pathway analyses and Web-Based Bioinformatics Tools (AnnotSV,DAVID, KEGG disease…) to detect CNVs potentially associated with breast cancer risk. Results: We identified both common and rare CNVs that may explain the familial breast cancer risk. The most relevant rare CNVs characterized affect PMS2, APC2 and PLEKHM1 genes. Among common CNVs potentially associated with breast cancer risk those encompassing UGT2B15/17, GSTT1, GSTT2 and GSTT2B genes are also associated with drug response and others affecting OR2T11, LPA, MUC20, LCE3C, HLA-DRB5, LGALS9B genes are associated with disease prognosis. Conclusion: Our study reveals new information concerning germline CNVs and breast cancer risk in Tunisian population. These finding suggest that collectively common CNVs along with rare CNVs could contribute to breast cancer predisposition. Likewise, CNVs affecting Lynch Syndrome genes require additional attention and should not be ignored in the genetic screening strategy of breast cancer patients.

Prevalence, risk factors and genetic associations for chronic kidney disease-related variables in four sub- Saharan African countries: an AWI-Gen sub-study Jean-Tristan Brandenburg (1), Jaya A George (2), June Fabian (3), Saraladevi Naicker (3),Ananyo Choudhury (1), Stuart Ali (1), Scott Hazelhurst (1) and Michele Ramsay (1) as members and collaborators of AWI-Gen and the H3Africa Consortium (1) Sydney Brenner Institute of Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (2) Department of Chemical Pathology, National Health Laboratory Services and University of Witwatersrand, Johannesburg, South Africa (3) Department of Internal Medicine, University of Witwatersrand, Johannesburg, South Africa BACKGROUND: The prevalence of chronic kidney disease (CKD) and genetic associations with kidney function- related variables in African communities is poorly documented. Our aim is to estimate the prevalence of CKD in six AWI-Gen study sites and to perform genetic associations with selected phenotypes. METHODS: Unrelated adult participants were recruited from four countries: four rural sites namely, Nanoro (Burkina Faso), Navrongo (Ghana), Agincourt and Dikgale (both in South Africa), and two urban sites, Nairobi (Kenya), and Soweto (South Africa). Participants completed a lifestyle questionnaire, had their blood pressure measured, blood and urine samples taken and DNA genotyped using the Illumina H3Africa SNV array. Serum creatinine was used to

9 | P a g e estimate glomerular filtration rate and urinary albumin and creatinine to assess albuminuria. CKD was defined as an eGFR < 60 ml/min/1.73m² and/or the presence of albuminuria (ACR > 3.0 mg/mmol). Stringent QC was performed on the genotyping data and imputation with African-enriched reference panels produced a SNV discovery set of ~15 million SNVs. Genome-wide association was performed with different indicators of kidney function, including eGFR, albumin creatinine ratio (ACR) (an indicator of albuminuria) and presence of CKD. FINDINGS: 10,702 participants between the ages of 40-60 years of age were recruited into the AWI-Gen study and 8,110 were included in the current analyses, following exclusion of individuals with missing data on key relevant variables. The adjusted overall prevalence using eGFR and albuminuria of kidney disease using the eGFR cut off was 2.2% (95% CI: 1.9-2.6) and of albuminuria was 9.4% (8.7-10.2). The overall prevalence of CKD was 10.9% (10.2-11.8) using eGFR and albuminuria. The prevalence of CKD was highest in South Africa (Agincourt 14.0% (11.9-16.4)) and was lowest in Burkina Faso (Nanoro 6.6% (5.9-7.9)). Age, female sex, hypertension, being HIV positive, and diabetes were all independently associated with CKD in these African communities. Preliminary results of the genetic associations showed replication of the involvement of the glycine amidinotransferase (GATM) gene variants in kidney function. CONCLUSION: CKD is an important public health problem in Africa and efforts should be directed at reducing common associated risk factors. Genetic analyses replicated the involvement of GATM in kidney function and further analyses are in progress.

The use of H3ABioNet node accreditation exercises in capacity building in Tunisia Melek Chaouch (1), Oussema Souiai (1) and Alia Benkahla (1) (1) Laboratory of Bioinformatics, biomathematics and biostatistics (Bims) The H3ABioNet node accreditation exercises are designed to assess the capacity of H3ABioNet nodes to properly process and analyses the NGS datasets that would typically be produced by H3Africa projects and beyond. The Tunisian node has opted for a strategy that enabled to foster students’ training. The accreditation exercises at Institut Pasteur de Tunis were conducted by Phd students and under the supervision of H3ABionet members. In addition to the guideline provided by H3ABionet, students are asked to conduct thorough literature review combined with the evaluation of the latest versions of the necessary tools. Evaluating, optimizing and benchmarking of the performance of the tools used for the exercises are an essential step before the pipeline validation. Workflows are implemented in a consistent, transparent and reproducible fashion (applying workflow manager: NextFlow), using first the test data then the real ones furnished by the Node Accreditation Exercises task force. Two accreditation exercises were completed by two different groups (16S rRNA diversity / Variant calling). First group was composed of students that have a metagenomics PhD project. Second group was composed of students that have a genetics PhD project. Students developed and tested their own pipelines and wrote a report that details all the steps taken. As a means of dissemination, these same students presented a Metagenomics (16S rRNA diversity) course to their colleagues at the Institut Pasteur in Tunis.

Targeted Next Generation Sequencing applied for the molecular characterization of MODY patients in Tunisia Hamza Dallali (1, 2), Serena Pezzilli (3, 4), Meriem Hechmi (1, 2), Om Kalthoum Sallem (5), Sahar Elouej (1, 6), Haifa Jmel (1, 7), Yosra Ben Halima (1, 8), Mariem Chargui (1), Mariem Gharbi (1), Luana Mercuri (3), Federica Alberico (3), Tommaso Mazza (9), Afaf Bahlous (10), Melika Ben Ahmed (11), Henda Jamoussi (1, 12), Abdelmajid Abid (1, 12), Vincenzo Trischitta (3, 4), Sonia Abdelhak (1, 8), Sabrina Prudente (3) and Rym Kefi (1, 8). (1) Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, Tunis 1002, Tunisia. (2) University of Carthage, National Institute of Applied Sciences and Technology, Tunis, Tunisia (3) Research Unit of Metabolic and Cardiovascular Diseases, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy. (4) Department of Experimental Medicine, Sapienza University, Rome, Italy. (5) Fattouma Bourguiba University Hospital, Monastir, Tunisia. (6) Aix Marseille University, Faculty of Medicine La Timone, INSERM, GMGF, 27 bd Jean Moulin 13385 Marseille, France. (7) University of Carthage, Faculty of sciences of Bizerte, Tunisia. (8) University of Tunis El Manar, 2092 El Manar I Tunis, Tunisia. (9) Unit of Bioinformatics, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (10) Central Laboratory of Medical Biology, Institut Pasteur de Tunis, BP 74, 13, place Pasteur, Tunis 1002, Tunisia.

10 | P a g e

(11) Laboratory of Transmission, Control and Immunobiology of Infections, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, Tunis 1002, Tunisia. (12) Research unit on obesity, National Institute of Nutrition and Food Technology, 11 rue Jebel Lakhdar, Bab Saadoun, 1007 Tunis, Tunisia. INTRODUCTION: Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with autosomal dominant inheritance pattern that classically presents before the age of 25 years. MODY has been recognized as a clinically and genetically heterogeneous condition with at least 14 subtypes caused by mutations in genes involved in the pancreas and beta-cell development as well as in insulin secretion. Therefore, the diagnosis of MODY and its subtypes is based on genetic testing. Our aim was investigating MODY by means of Next Generation Sequencing in the Tunisian population. METHODS: Targeted Next Generation sequencing of 27 monogenic diabetes genes was carried out in eleven phenotypically suspected Tunisian patients. We filtered the genetic variants according to the reads depth and quality, their frequencies in public databases and their predicted functional impact evaluated by bioinformatics prediction tools, clinical features of patients as well as an extensive literature search for reported clinical and functional studies. RESULTS: Five heterozygous variants were found in four patients. They include two mutations in HNF1A and GCK that are the causative genes of the two most prevalent MODY subtypes described in the literature. Other possible mutations, including novel frameshift and splice site variants were identified in the ABCC8 gene, responsible for MODY 12 subtype. CONCLUSION: Our study is the first to investigate the clinical application of tsargeted Next-Generation Sequencing for the diagnosis of MODY in Africa. The combination of this approach with a filtering/prioritization strategy made a step towards the identification of MODY mutations in the Tunisian population. However, our findings indicate that the most frequently reported genes are not apparently the major genes involved in MODY in our population. In this context, exome sequencing presents an alternative to look for genetic variants not currently reported genes.

The importance of considering natural isotopes in improving protein identification accuracy. Sara El-Jadid (1), Raja Touahni (1) and Ahmed Moussa (2). (1) Faculty of science, Ibn Tofail University, Kenitra, Morocco (2) National School of Applied Science, Abdelmalek Essaadi University, Tangier, Morocco Many tools in proteomics are based on accurate identification of peptide contained in a sample. In fact, the issue of identification is the foundation of the entire proteomics workflow, where all subsequent steps depend on the quality of data generated at the beginning. The accuracy of data generated allows, not only to have good results but also to ensure consistency at the end of the analysis. There is a consensus about the factors that affect this accuracy. It's popularly assumed that exploiting physics and chemistry of peptide sequences can improve the identification accuracy. In fact, considering natural isotopes when quantifying peptides will considerably improve results. This paper presents findings that defend such a view. We explored the mass difference between the nominal mass (which considers the most abundant isotope of each element) and the mean mass (which consider the abundance of each element). We noticed that within a biomolecule, the larger the number of elements, the less this difference is negligible. In accordance with that, peptide misidentification is due to the previously explained variance. These findings reveal that including natural isotopes during quantification will play a robust role in improving identification accuracy. This study could lead us to design alternative identification tools combining better sensitivity and specificity.

A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study. Cherif Ben Hamda (1,2,3), Raphael Sangeda (4), Liberata Mwita (4), Ayton Meintjes (5), Siana Nkya (4), Sumir Panji (5), Nicola Mulder (4), Lamia Guizani-Tabbane (2,6), Alia Benkahla (1,2), Julie Makani (4), Kais Ghedira (1,2), H3ABioNet Consortium. (1) Laboratory of Bioinformatics, Biomathematics and Biostatistics, Institute Pasteur of Tunis, Tunis, Tunisia. (2) University of Tunis El Manar, Tunis, Tunisia. (3) Faculty of Science of Bizerte, Jarzouna, University of Carthage, Tunisia. (4) Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. (5) University of Cape Town, Cape Town, South Africa. (6) Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institute Pasteur of Tunis, Tunis, Tunisia. A chronic inflammatory state to a large extent explains sickle cell disease (SCD) pathophysiology. Nonetheless, the principal dysregulated factors affecting this major pathway and their mechanisms of action still have to be fully

11 | P a g e identified and elucidated. Integrating gene expression and genome-wide association study (GWAS) data analysis represents a novel approach to refining the identification of key mediators and functions in complex diseases. Here, we performed gene expression meta-analysis of five independent publicly available microarray datasets related to homozygous SS patients with SCD to identify a consensus SCD transcriptomic profile. The meta-analysis conducted using the MetaDE R package based on combining p values (maxP approach) identified 335 differentially expressed genes (DEGs; 224 upregulated and 111 downregulated). Functional gene set enrichment revealed the importance of several metabolic pathways, of innate immune responses, erythrocyte development, and hemostasis pathways. Advanced analyses of GWAS data generated within the framework of this study by means of the atSNP R package and SIFT tool identified 60 regulatory single-nucleotide polymorphisms (rSNPs) occurring in the promoter of 20 DEGs and a deleterious SNP, affecting CAMKK2 protein function. This novel database of candidate genes, transcription factors, and rSNPs associated with SCD provides new markers that may help to identify new therapeutic targets.

Genomic characteristics of Invasive Streptococcus pneumoniae serotype 1 in New Caledonia, a region in Oceania with a high incidence of serotype 1 outbreaks Mariem Hanachi* (1), Anmol Kiran (2), Jen Cornick (2), Dean Everett (2), Alia BenKahla (1), Oussema Souiai (1) (1) Laboratory of Bioinformatics, BioMathematics & BioStatistics, Institute Pasteur of Tunis (2) Malawi-Liverpool-WellcomeTrust, Malawi

INTRODUCTION: Streptococcus pneumoniae (SP) is a major cause of global morbidity and mortality especially in children and elderly. Despite of numerous vaccination campaigns (Pneumococcal conjugate vaccines PCV10 and PCV13 ), Serotype 1 remains the most common cause of global invasive pneumococcal disease and represents the most prevalent serotype in New caledonia (NC) with two major outbreaks reported in the 2000’s. OBJECTIVES: In our study, we took advantages of Whole Genome Sequencing (WGS) to describe the genomic features characterizing the invasive Streptococcus pneumoniae Serotype 1 in New Caledonia. METHODOLOGY : We performed a WGS of 67 SP1 isolates collected before PVC13 introduction. Phenotypic meta- data (isolation date, age, source) for each isolate were also collected. We performed Bioinformatic analysis to assess sequence type and the key virulence factors in the study population as well as the mobile genetic elements carrying antimicrobial resistance genes (ATB). Furthermore, we measured the level of recombination in the study population and identified recombination ‘hotspots’. RESULTS : MLST analysis of the samples revealed two sequence types (ST) : ST306 and ST3717. Investigation of accessory genomes uncovered the presence of ubiquitous ATB for macrolide, lincosamide antibiotic and fluoroquinolone. Virulence patterns were differentially distributed between isolates and involved in several steps of SP infection process. We also reported a high rate of recombination among which some of its hotspots occurred in virulence and antibiotic resistance associated genes in the population. We dated the emergence of NC SP serotypes to the early 1980s DISCUSSION: We analysed the SP Serotype 1 samples from NC aiming at better characterising their genomic features. We interestingly depicted the uniqueness of ST3717 in NC. Macrolide resistance coding gene was identified in our ATB resistance analysis. This case is rarely observed, suggesting an increasing emergence of macrolide resistant clones in the region. Our analysis corroborated previous studies confirming the involvement of recombination mechanisms in ATB and virulence patterns transmission. NEXT STEPS: In a subsequent study, it would be worthy to collect SP1 isolates in New Caledonia to compare the impact of PVC13 introduction on SP recombination rates, virulence genes and population structure in the region.

Transcriptional Signatures of Active TB Disease in HIV co-infected Children in Uganda and Botswana Eric Katagirya (1), Graeme Mardon (3), Eddie Wampande (2), Moses Joloba (1), Neil Hanchard (3). (1) Department of Immunology and Molecular Biology, Makerere University College of Health Sciences. (2) Department of Biotechnical and Diagnostic Sciences, Makerere University College of Veterinary Medicine and Bio-Resources. (3) Dept. of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston Tx 77030 INTRODUCTION: Diagnosis of tuberculosis (TB) is problematic in individuals co-infected with HIV because of the atypical presentation of the disease, low infective dose of the organisms among other reasons. The difficulty is further compounded in children as there is added difficulty in the collection of appropriate quantity and quality of sputum. There is, therefore, need for alternative markers of disease. In this study, we use RNA sequence data from

12 | P a g e

HIV infected children with different clinical TB phenotypes i.e. possible, probable and confirmed TB as well as non- TB infected children to determine the transcriptional signature for Active TB and/or different clinical phenotypes. METHODS: IRB approval was obtained from the two study sites in Botswana and Uganda and RNA collected as a case-control study. RNA samples from a discovery data set of 24 Active TB cases and 24 non-TB infected age and gender-matched controls were sequenced on the Illumina HiSeq platform. FastQC was used for Quality Control of the sequences. The sequences were then aligned against the Human Reference Genome using Bowtie2/Cufflinks2. Transcriptome assembly was done using Cufflinks2 while differential gene expression was determined using CuffDiff2. CuffDiff2 determined the fold change in gene expression (normalized to log base 2). Geneset enrichment analysis was done using the GSEA desktop platform (Broad Institute) on the over 20,000 genes identified and ranked by fold change in expression. Multidimensional scaling (MDS) was done using the Orange Data Mining software. RESULTS AND FUTURES DIRECTIONS: Over 20,000 genes were identified in the cases and controls with 1500 and 300 genes upregulated and downregulated respectively in the cases. The gene set enrichment analysis showed enrichment of genes in gene sets involved in innate immunity and cytokine pathways. In conclusion, active TB disease upregulates gene expression of genes involved in innate immunity. We also show that whole blood gene expression profiles may be able to delineate clinical TB phenotypes. Future directions include additional deconvolution of the gene expression to include cell subsets as covariates. We shall also validate the transcription signatures on secondary data set of samples from Uganda, Botswana, and Swaziland.

Homology modeling and docking of AahII-Nanobody complexes reveal the epitope binding site on AahII scorpion toxin Ayoub Ksouri (1), Kais Ghedira (2), Rahma Ben Abderrazek (1), B.A. Gowri Shankar (3), Alia Benkahla (2), Ozlem Tastan Bishop (4), Balkiss Bouhaouala-Zahar (1, 5) * (1) Laboratoire des Venins et Molecules Therapeutics, Institut Pasteur de Tunis, 13 Place Pasteur, BP74, Tunis Belv ed ere- University of Tunis El Manar, Tunisia (2) Laboratory of BioInformatics, Biomathematics and Biostatistics (BIMS), Institut Pasteur de Tunis, 13 Place Pasteur, BP74, Tunis Belv ed ere- University of Tunis El Manar, Tunis, Tunisia (3) Laboratory for Venom Peptidomics and Molecular Simulation Bannari Institute of Technology, Alathukombai, Post Sathyamangalam, 638 401, Erode District, Tamil Nadu, India (4) Research Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa (5) Faculte de Medecine de Tunis, 15 rue Djebel Lakhdhar, La Rabta, 1007-Universit e Tunis El Manar, Tunisia Scorpion envenoming and its treatment is a public health problem in many parts of the world due to highly toxic venom polypeptides diffusing rapidly within the body of severely envenomed victims. Recently, 38 AahII-specific Nanobody sequences (Nbs) were retrieved from which the performance of NbAahII10 nanobody candidate, to neutralize the most poisonous venom compound namely AahII acting on sodium channels, was established. Herein, structural computational approach is conducted to elucidate the Nb- AahII interactions that support the biological characteristics, using Nb multiple sequence alignment (MSA) followed by modeling and molecular docking investigations (RosettaAnti- body, ZDOCK software tools). Sequence and structural analysis showed two dissimilar residues of NbAahII10 CDR1 (Tyr27 and Tyr29) and an inserted polar residue Ser30 that appear to play an important role. Indeed, CDR3 region of NbAahII10 is characterized by a specific Met104 and two negatively charged residues Asp115 and Asp117. Complex dockings reveal that NbAahII17 and NbAahII38 share one common binding site on the surface of the AahII toxin divergent from the NbAahII10 one's. At least, a couple of NbAahII10 e AahII residue interactions (Gln38 e Asn44 and Arg62, His64, respectively) are mainly involved in the toxic AahII binding site. Altogether, this study gives valuable insights in the design and development of next generation of antivenom.

Benchmarking of RNAseq data analysis. Pierre-Jean Laclide, Aymen Ben Chaalia, Alia Benkahla, Oussema Souiai Laboratory of Bioinformatics, biomathematics and biostatistics (Bims), Institut Pateur de Tunis, Tunisia. INTRODUCTION: RNA-sequencing has numerous applications, ranging from differential gene expression detection to transcript discovery. RNAseq data analysis pipeline includes three phases: quality checking (phase 1), alignment/mapping (phase 2) and statistical analysis of the reads counts (phase 3). METHODOLOGY: Considering the plethora of tools using different statistical tests aiming at identifying differentially expressed genes, we benchmarked different tools for each phase of the analysis :

13 | P a g e

(1)FastQC and NGSQC for data quality check, Trimmomatic and Trim_Galore for the trimming of raw data; (2) STAR, HISAT2 and SOAPSPLICE for mapping, read-alignment and gene-count generation; (3) and edgeR and DESeq2 for the downstream statistical analysis. For each phase we point out the challenges faced by each tool, and suggest ways to overcome them. CONCLUSION: Thus, we are elaborating on-demand pipelines with a workflow manager ( NextFlow ) involving the various tools selected above. Runtime analysis and accuracy are our main selection criteria for the set of selected tools.

Tunisians Youth Literacy to Seasonal Influenza: Antibiotics Versus Empathy Foued Maaoui (1), Imen Moumni (2) (1) ISEFC, Virtual University of Tunis, Tunisia (2) Laboratory of molecular and cellular hematology, Pasteur Institute of Tunis, Tunisia INTRODUCTION: In Tunisia, seasonal influenza is a public health problem that affects mainly youth. Hygiene measures prescribed by the health authorities remain limited in the population. OBJECTIVES: For implementation of an educational intervention to improve preventive measures in primary and secondary schools and to be aware of the inappropriate antibiotic consumption risks, this study will assess young Tunisians' literacy towards Seasonal Influenza. Health education, socio-demographic (gender and intersectionality) and media variables will be explored. METHODS: This is a cross-sectional study, which included Tunisian students from different educational levels and residents in different regions of the country. PRELIMINARY RESULTS: The results show that the risk perception and level literacy depend on gender, geographical proximity, media coverage and didactic choices.The fears of male students in preparatory or secondary school focus significantly more than for female school students around seasonal flu, respectively (21.5% vs. 10%, p)

Whole Exome Sequencing reveals differential frequencies in ancestral alleles in Hearing Impairment genes among patients compared controls in Cameroon Noluthando Manyisa (1), Emile R. Chimusa (1), Collet Dandara (1), Ambroise Wonkam (1,2) (1) Division of Human Genetics, Department of Pathology, University of Cape Town, Cape Town, South Africa (2) Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa INTRODUCTION: Hearing impairment (HI) is the most common sensory disorder, affecting 466 million people worldwide, with the highest incidence in Sub-Saharan Africa. Up to 50 % of congenital HI is due to genetic factors; with 70% that are non-syndromic HI (NSHI). HI is associated with over 150 genes, of which GJB2 and GJB6, are the most prevalent in populations of European and Asian descent, but not in populations of African ancestry. OBJECTIVES: This study used Whole Exome Sequencing (WES) to, 1) determine the rates for putative pathogenic variants in 159 known HI associated genes, among 18 Cameroonian patients, and 2) compare the fraction of ancestral and derived alleles among patients and 129 ethnically matched controls. METHODS: Exomes were annotated using the VCFtools ‘fillOaa’ script. Variant annotation was performed using Annovar and filtered based on rarity and pathogenicity. Putative pathogenic variants were validated by Sanger sequencing. Protein-protein interaction analysis was performed with a custom python and R script, and pathways enrichment analysis used Enrichr combined with a second custom R script. The proportion of derived and ancestral alleles was computed by downloading the SNP ancestral alleles from Ensembl and verifying the presence of the SNPs in dbSNP database. RESULTS: Putative deleterious variants were found in MYO3A, MYO15A and COL9A3, in three, four and two patients, respectively; but were not confirmed by direct Sanger Sequencing and viewing the patients’ BAM files. At a population level, specific genetic variations were identified in FOXD4L2, DHRS2L6, RPL3L and VTN, that interacted with other HI associated pathways. In known HI genes, the proportion of ancestral alleles was lowest for the patients’ population for variations at minor allele frequencies below 0.1. The results showed a low pick up rate of putative variants in known genes in this group of Cameroonian patients with NSHI. Differential frequencies of ancestral vs derived alleles were found in HI genes among patients vs controls, and underline, for the first time, the possibility of multigenic influence in Congenital Hearing Impairment. FUTURE WORK: These findings may signal an evolutionary enrichment of some variants of HI genes in the Cameroonian population and deserve further investigation.

Sputum microbiome composition through treatment of TB patients in an endemic setting Monica M Mbabazi (1), David P Kateete (1), Faith Nakazzi (1), Fred A Katabazi (1), Edgar Kigozi (1), Dunstan Kalanzi (2), Lydia Nakiyingi (3,4), Moses L Joloba (1), Adrian Muwonge (5)

14 | P a g e

(1) Department of Immunology & Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda (2) Department of Medicine, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda (3) Department of Dentistry, School of Health Sciences, Makerere University College of Health Sciences, Kampala, Uganda (4) Infectious Diseases Institute, Makerere University College of Health Sciences, Mulago Hospital Complex, Kampala, Uganda (5) Division of Genetics and Genomics, Division of Infection and Immunity, The Roslin institute, University of Edinburgh, Edinburg, UK INTRODUCTION: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb is responsible for a large number of deaths globally, and the World Health Organization (WHO) ranks it among the top 10 causes of death. TB diagnosis and treatment approach aims at a single pathogen, neglecting the community were Mycobacterium resides which may explain why TB disease remains a global health problem. OBJECTIVE: The overall aim of this study was to generate insight into the microbiome composition in pulmonary TB patients in Uganda, and its changes through TB therapy using sputum samples, the most important and widely used clinical specimen in TB patients, as a proxy for characterizing the lung microbiome composition. METHODS: After IRB approval, induced sputum was longitudinally collected from 120 participants. These samples were collected at baseline, and follow-up visits after 2 and 5 months of anti-TB therapy initiation. Total microbial DNA was extracted using the QIAamp DNA Mini Kit and the V4-V5 region of the 16S rRNA gene was PCR amplified and the amplicons were verified using highthroughput gel-electrophoresis. DNA was sequenced on Illumina Miseq and microbial community analysis was done using the QIIME 2 pipeline. RESULTS: We obtained a total count of 93116821 sequence reads equivalent to 3.6 GB in a zipped format, these belonged in kingdom bacteria and archaea and a small proportion that was unclassified. At the kingdom level, bacteria were the most dominant with 26 phyla that were observed and the first six highly abundant phyla in this kingdom were: Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Actinobacteria, and Cyanobacteria. Based on the Unweighted unifrac beta diversity Metrix, TB treatment showed an impact on these bacterial communities by affecting their abundance and diversity hence implying that this treatment may lead to a state of dysbiosis. We observed the high abundance of phylum Fusobacteria, Spirochetes, Bacteroidetes, Tenericutes and Cyanobacteria in patients with poor treatment outcome. NEXT STEP: We look forward to doing shotgun sequencing to better understand the role of the observed taxa in this environment where they reside. This will also aid us in understanding the interaction of these microbes in causing and preventing disease.

BRCA1-c.211dupA a recent founder mutation in Tunisian breast cancer patients: implication on clinical management and early disease detection Najah Mighri (1), Yosr Hamdi (1), Maroua Boujemaa (1), Sonia Ben Nasr(1,2), Nesrine Mejri (1,3), Houda El Benna (3), Soumaya Labidi (1,3), Jihen Ayari (1,2), Mehdi Balti (1,2), Asma Chikhaoui (1), Houda Yacoub- Youssef (1), Olfa Jaidene (4), Mariem Ben Rekaya (1), Lilia Romdhane (1,5), Rym Kefi (1), Ridha M’rad (6), Abderrazek Haddaoui (2), Khaled Rahal (4), Samir Boubaker (1), Hamouda Boussen (1,3), Sonia Abdelhak (1), on behalf of PEC consortium3.

(1) University of Tunis El Manar, Institut Pasteur de Tunis, LR16IPT05 Laboratory of Biomedical Genomics and Oncogenetics,1002, Tunis, Tunisia. (2) Department of Medical Oncology, Military Hospital of Tunis, Mont Fleury-1008 Tunis, Tunisia. (3) Department of Medical Oncology, Abderrahmane Mami Hospital, 2080 Ariana, Tunisia (4) Surgical Oncology Department, Institute Salah Azaiez, Boulevard 9 Avril 1938 Beb Saadoun, 1006 Tunis, Tunisia (5) Department of Biology, Faculty of Science of Bizerte, Université Tunis Carthage, Zarzouna, Tunisia (6) Department of Hereditary and Congenital Disorders, Charles Nicolle Hospital, Tunis, Tunisia. Breast cancer is the most commonly diagnosed cancer in women worldwide. So far, almost half of the genetic component of breast cancer is explained by genetic variation. Germline mutations in the BRCA1 gene explain a high proportion of hereditary breast cancer cases and show substantial ethnic and geographical differences. The c.211dupA-BRCA1 mutation seems to be specific to the Tunisian population since it is only reported in the Tunisian cohorts. In our study, we focused our analysis on the screening of this mutation in a total of 85 breast cancer cases in order to assess its founder effect and to estimate its age. We also aimed to analyze clinicopathological features among carriers. Haplotype analysis was performed using microsatellites markers. DMLE+2.3 software was used to

15 | P a g e estimate the mutation age. Six carriers of c.211dupA mutation were identified, all originating from Nabeul, a governorate at the North-eastern part of Tunisia. All carriers shared an identical disease haplotype (170-145-147) that was absent in non-carriers and in control chromosomes. Haplotype analysis confirmed the founder effect and showed that c.211dupA is a recent mutation aged approximately 130 years. Investigation of the clinicopathological features among carriers showed that the c.211dupA mutation could be associated with contralateral recurrence, aggressive triple negative breast cancer form, and ovarian cancer phenotype. The identification of a founder mutation has a significant impact on clinical management of at-risk individuals from a restricted area. Based on these results, we recommended the prioritization of c.211dupA mutation screening in breast and ovarian cancer patients originating from North-east of Tunisia for better clinical management of these cancer patients.

Pleiotropic effects of molecular and cellular factors in sickle cell anemia Moumni Imen*(1), Neila Eleichi (1), Mbarka Barmate (1), Houyem Ouragini (1), Chaouachi Dorra (1), Monia BenKhaled (2), Mohamed Bejaoui (2), Abbes Salem (1) et Samia Menif (1) (1) Laboratoire d'hématologie moléculaire et cellulaire, Institut Pasteur de Tunis, 13 Place Pasteur, BP 74, 1002 Tunis Belvédère, Tunisie. (2) Service d'Immuno-Hématologie pédiatrique, Centre National de Greffe de Moelle Osseuse, Tunis, Tunisie INTRODUCTION: Sickle cell anemia (SCA) is a monogenic disease, in which the severity and symptoms vary widely. This heterogeneity is particularly dependent on fetal hemoglobin (HbF) levels in SCA patients: high HbF levels are known to moderate SCA disorders. Genome wide association studies reported that HbF levels variation in SCA patients are associated to several SNPs on the GPM6B gene (Xp22.2). Also, recent studies suggest that there are cellular factors contribute to the clinical variation of this disease, such as eryptosis and microparticles (MPs). OBJECTIVES: We aim to verify these finding and determine an association between the genetics factors: HbF expression and GPM6B loci, cellular factors: eryptosis and microparticules, and sickle cell anemia in Tunisia. Methodology: Following clinical diagnosis, homozygous SCA patients were sampled for hematological, molecular and cellular assays. SSP-PCR was performed on the targeted GPM6B loci for molecular explorations. A flow cytometry cellular study was performed by evaluating the number of circulating microparticles as well as their cellular origin by triple labeling with Annexin V / Ac anti CD41 / Ac anti CD235a and the exploration of eryptosis by determining the viability parameters of red blood cells: the appearance of their morphology, the exposure of PS to the GR surface by annexin V labeling and the determination of intracellular calcium concentration by Fluo3-am labeling. PRELIMINARY RESULTS AND CONCLUSION: The outcome of our study indicated a correlation between the GPM6B gene and the variations of HbF level, it could be considered as one of the modulator element of SCA. As to the cellular finding show that Eryptosis in sickle cell patients is triggered by Ca2 + entry and narrowing of red blood cells. For the study of MPs, the increase in Platelets MPs suggests that platelets may contribute to vaso-occlusive crisis in sickle cell patients. NEXT STEPS: The externalization of PS is not always correlated with the increase in cytosolic calcium concentration, we must explore other viabilities parameters of erythrocytes such as accumulation of ceramide and ERO. On the other hand, to be continued the cellular exploration in other hemoglobinopathies

Whole-exome sequencing of sickle cell disease patients with hyperhemolysis syndrome suggests a role for rare variation in disease predisposition. Savannah Mwesigwa (1,2,3), Joann Moulds (4), Alice Chen (5), Jonathan Flanagan (6,7), Vivienne Sheehan (6,7), Alex George (7), Neil Hanchard (1,6,2). (1) Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. (2) Collaborative African Genomics Network (CAfGEN), Gaborone, Botswana. (3) Makerere University, Kampala, Uganda. (4) Scientific Support Services, LifeShare Blood Centers, Shreveport, Louisiana. (5) St Luke's Episcopal Hospital. (6) Department of Pediatrics, Baylor College of Medicine, Houston, Texas. (7) Texas Children's Hospital, Houston, Texas. BACKGROUND: Hyperhemolysis syndrome (HHS) is an uncommon, but the life-threatening, transfusion-related complication of red blood cell transfusion. HHS has predominantly been described in patients with sickle cell disease (SCD) and is difficult to diagnose and treat. The pathogenesis of HHS, including its occurrence in only a subset of apparently susceptible individuals, is poorly understood. We undertook whole-exome sequencing (WES) of 12 SCD-HHS patients to identify shared genetic variants that might be relevant to the development of HHS.

16 | P a g e

METHODS: DNA from adults with SCD having at least one previous episode of HHS were subject to WES. High- quality variants were passed through a series of bioinformatics filters to identify variants that were uncommon among African populations represented in public databases. Recurrent, putative loss-of-function variants occurring in biologically plausible genes were prioritized and then genotyped in a larger, ancestry-matched cohort of non- HHS controls. RESULTS: A rare, heterozygous stop-gain variant (p.Glu210Ter) in MBL2 was significantly enriched among HHS cases (p = 0.002). This variant is predicted to result in a premature termination codon that escapes nonsense-mediated mRNA decay, potentially leading to a novel phenotype. We also observed a complex insertion-deletion variant in the final exon of KLRC3 that was enriched among cases (p = 0.0019), although neither variant was found among seven pediatric SCD-HHS patients. CONCLUSION: Our results suggest a potential role for rare genetic defects in the development of HHS among adult SCD patients. Such enriched variants may ultimately be useful for identifying high-risk individuals and informing therapeutic approaches in HHS.

PRIMO: modeling protein complexes and building biological assemblies Margaret Nabatanzi (1), Özlem Tastan Bishop (1) (1) Research Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa INTRODUCTION: As evolution drives proteins to larger sizes, oligomeric proteins with the exception of those that function as monomers are becoming more common. Thus, it becomes increasingly essential to study protein- protein interfaces, modeling protein complexes and building large proteins (biological assemblies) that are not part of the asymmetric unit. Given the complexity of protein complexes, a few servers have been developed to model protein multimers. Here, we present an extended version of Protein Interactive Modeling (PRIMO) pipeline for modeling protein complexes and building large biological assemblies. PRIMO will be linked to HUMA to model and analyse the new disease related variations identified in African populations and specifically help to analyse the effects of the SNPs located in protein-protein interfaces. PRIMO is an interactive and user-friendly web server for both novice and experienced users. METHODS: PRIMO provides a step-by-step process: template identification, target-template alignment, modeling and optional building of biological assemblies of oligomers. As with the original PRIMO, the new extended version was implemented using Python for the backend scripts with Django used to develop and manage the user interface and overall application. JavaScript with its libraries (JQuery, Knockout JS, AJAX) were used for asynchronous call between PRIMO and Job Management System (JMS). RESULTS: Input amino acid one letter sequence(s) can either be pasted in fasta format or uploaded as a file. Homologous templates to the target sequence(s) are returned in a tabular form including the appropriate metrics to guide the user to manually select the suitable template(s). If the user chooses to build a biological assembly after modeling of the asymmetric unit, the corresponding oligomeric state and symmetry information for the existing biological assembly is provided too. Besides the tabular form, a webGL based protein and a multiple sequence alignment viewer is also included for protein structural visualisation and pairwise sequence alignment respectively. The user can manually edit the alignment of the final chosen template and then the final model(s) are returned with the corresponding evaluation results. NEXT STEPS: Development of the user interface for the biological assembly building step. Testing of the pipeline for protein complexes to ascertain its accuracy and submit it for continuous assessment to Continuous Automated Model EvaluatiOn (CAMEO). Linking the extended functionality of PRIMO to HUMA.

Abnormal monocyte phenotypes, immune activation, and inflammation persist despite long-term antiretroviral therapy in an African cohort Rose Nabatanzi (1), Lois Bayigga (1), Moses Joloba (1), Sarah Rowland Jones (2,3), Stephen Cose (4), Damalie Nakanjako(5,6) (1) Department of Immunology and Molecular Biology, Makerere University College of Health Sciences, Kampala, Uganda (2) Nuffield Department of Medicine, University of Oxford, United Kingdom (3) MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda (4) Department of Clinical Research, LSHTM, London, UK (5) Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda (6) Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda

17 | P a g e

BACKGROUND: Antiretroviral therapy (ART) has greatly improved the life expectancy of HIV-infected people worldwide. Despite this improvement, defects persist in both innate and adaptive immune responses. We examined monocyte phenotype and function in individuals who had received ART with viral suppression for seven years. We hypothesized that HIV-infected individuals have poorer monocyte function than their HIV-negative counterparts and this could negatively affect their adaptive immune responses making them more susceptible to opportunistic infections. METHODS: In a cross-sectional study, we compared monocyte phenotypes and function among HIV-infected ART- treated adults with restored CD4 to 500 cells/µl, with age-matched healthy HIV-negative individuals. Using flow cytometry, monocyte subsets and function were determined including cytokine production (TNF, IL-6, and IL-1ß) and expression of co-receptors necessary for antigen presentation (CD86 and CD40). Microbial translocation (IFAB- P, LBP, and LPS), monocyte activation (sCD14) and inflammation (IL-6 and D-dimer) were measured using ELISA. Data was analyzed using Flow jo 10.1; and Stata version 13. Mann Whitney tests were carried out for statistical analysis. RESULTS: In HIV-infected people on long-term ART, non-classical monocytes (CD14+, CD16++) were significantly lower than in HIV negative individuals, (P=0.01). IL-1ß production by monocytes and expression of costimulatory molecules (CD40 and CD86), were lower among HIV-infected than HIV-negative individuals (P= 0.0001), (P=0.01) and (P=0.02) respectively. Gut mucosal damage as expressed by Intestinal Fatty Acid Binding protein (IFAB-P) was higher in HIV-infected than in HIV-negative individuals (P=0.002). Monocyte activation (sCD14, P= 0.0017) and inflammation (IL-6, P= 0.04) were persistently higher among ART-teared HIV-positive individuals than among the healthy HIV individuals. CONCLUSION: Our data shows an incomplete recovery of monocyte subset and function among HIV-infected adults after seven years of suppressive therapy. Further investigations are required to understand drivers of abnormal monocyte function despite long-term ART. This will lead to the development of interventions to improve immune recovery among ART-treated individuals

The developmentally dynamic microRNA transcriptome of Glossina pallidipes tsetse flies, vectors of sleeping sickness and animal trypanosomiasis Careen Naitore (1,2), Joel L Bargul (1,2), Alan Christoffels (3), Daniel Masiga (1), Villinger Jandouwe (1) (1) Molecular Biology and Bioinformatics Unit, International Center of Insect Physiology and Ecology (icipe), Nairobi, Kenya (2) Department of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya. (3) South African Bioinformatics Institute (SANBI), South African MRC Bioinformatics Unit, University of the Western Cape, Bellville, South Africa. INTRODUCTION: Tsetse flies are holometabolous biological vectors that transmit trypanosome parasites responsible for human African trypanosomosis (HAT or sleeping sickness) and African animal trypanosomosis (AAT). Although a concerted multi-agency effort led by the WHO over the last few decades has resulted in a significant reduction in the incidence of sleeping sickness, AAT is still the economically most important livestock disease in sub-Saharan Africa. Despite this, little known about the role of vector genes in the transmission of parasites. METHODS: We used Illumina Hiseq 2500 to generate small RNA libraries at different developmental stages (larvae, pupae, teneral, and reproductive adults) and sexes of Glossina pallidipes, the major vector of Trypanosoma brucei brucei in eastern Africa. Small non-coding micro (mi)RNAs, which are crucial in regulating several biological processes such as cell development, differentiation, embryogenesis, metamorphosis, and vector competence were identified by miRDeep2. Their expression profiles at different stages and sexes were analyzed with edgeR in the R programming language. RESULTS: We identified 125 mature miRNA genes, including 10 novel miRNA unique to G. pallidipes. Most (109) miRNA were expressed in all developmental stages, three were pupae specific, 13 were adult specific and four were upregulated in females compared to males in adult stages, while 16 miRNA were upregulated and three miRNA were downregulated in females compared to males in the reproductive adult stages. Moreover, we found 43 and 41 miRNAs that were significantly expressed in the transition from pupae to teneral males and teneral females, respectively, suggesting they may play a crucial role in metamorphosis and reproduction. We found the miR-263 family, which has also been shown to regulate organogenesis in Drosophila melanogaster pupae, to be up-regulated in the pupal stage of G. pallidipes. This group of miRNA could, therefore, be exploited for tsetse fly control by engineering to disrupt organ development Future directions include functional analysis of the miRNAs by determining the target genes (mRNA) and hence determining the gene ontology annotations. CONCLUSIONS: Since miRNAs have also been associated with the regulation of host-pathogen interaction, this study serves as a baseline for investigating the use of miRNAs for controlling vector-borne diseases.

18 | P a g e

Evaluation of Microorganisms Population from Cattle Egret Droppings in a Residential Area in Ogun State, Nigeria. C. Nwankwo (1,2), O.A. Oyelana (1), A.O. Aduramigba-Modupe (1), O.A. Folarin (1,2), I.O.O. Komolafe (1,2), C.T Happi (1,2) (1) Department of Biological Sciences, Redeemer’s University (RUN), Ede, Osun State, Nigeria. (2) African Centre of Excellence for Genomics of Infectious Diseases (ACEGID). Reports on zoonotic infections are on the increase especially in developing countries where infectious diseases are prevalent. The objective of this study was to evaluate the microorganism population present in a residential area colonized by Cattle Egrets (migratory birds) and to ascertain the antibiotics susceptibility patterns of bacterial isolates. Soil, water, leaves and cattle egrets droppings were collected from a residential area with a tree inhabited by the birds. Microorganisms were isolated and characterized by serially diluting, streaking, incubating and observing the colonies.The bacterial and fungal counts,stainings,morphological characterizations, biochemical tests (motility, indole, urease, catalase, oxidase and sugar utilization tests) and antibiotic sensitivity testsusing antibiotic disks and comparing against a MacFarland standard were done and compared with appropriate controls. The mean bacterial counts are as follows: Soil (328.50x104CFU/ml), Water (240.92x104CFU/ml), Leaf (75.00x104CFU/ml), Feaces (47.00x104CFU/ml), Air (217.00x104CFU/ml). The bacteria species isolated include Salmonellaspp, Staphylococcusspp, Shigellaspp,Escherichiacoli, Edwardsiellasp, Kurthiasp, and Proteusspp. The fungi isolated from the samples were Aspergillusspp, Mucorspp, Rhizopusspp and Rhodotorulaspp. The antibiotics susceptibility of the bacteria isolated were determined using ampicillin, chloramphenicol, erythromycin, gentamycin, penicillin, streptomycin and tetracycline.Of all the bacteria isolated from the samples analyzed, gentamycin showed the highest (26 of 30) sensitivity while the highest level of resistance (100%) by the isolates was reported in penicillin. In conclusion, cattle egrets are capable of spreading zoonotic, pathogenic and antibiotic resistant bacteria and fungi and should not be encouraged near human habitation. However, further genomics study to identify and characterize the organisms that cannot be identified by microbiology methods is recommended

Metagenomic analysis of blood samples obtained from febrile patients in Nigeria Judith U. Oguzie (1,2) , Philomena Eromon (1), Paul Oluniyi (1,2), Katherine J. Siddle (3), Ikponmwosa Odia (4), Sarah M. Winnicki (3), Samar Mehta (3), Iguosadolo Nosamiefan (1), Kayla G. Barnes (3), Daniel J. Park (3), Eghosa Uyigue (1,2), Tolulope Kayode (1,2), Fehintola Ajogbasile (1,2), Jessica Uwanibe (1,2), Sylvanus Okogbenin (4), George Akpede (4), Peter O. Okokhere (4), Onikepe A. Folarin (1,2), Pardis C. Sabeti (3) and Christian T. Happi (1,2). (1) African Center of Excellence for Genomics of Infectious Diseases, (2) Department of Biological Sciences, Redeemer’s University, Ede, Osun State, Nigeria (3) Broad Institute of MIT and Harvard (4) Irrua Specialist Teaching Hospital, Edo State, Nigeria INTRODUCTION: Fever, a common but non-specific sign of many infectious diseases can lead to misdiagnosis and overdiagnosis. This has great impact on spread of infectious disease as accurate and timely diagnosis is necessary for timely management and control of disease. In countries where infectious disease is endemic, there is high prevalence of co-infection of these diseases. There is therefore need to identify all possible infections present in order to inform management of such febrile case. In addition, knowledge of the pathogens may enable understanding of the pathogenesis and possible interactions between pathogens. The advent of next generation sequencing (NGS) which allow for metagenomic analysis enables sequencing of whole genomes of all organisms present in samples without prior knowledge. In addition, NGS also enable characterization of all pathogens present in such samples. OBJECTIVE: This study therefore, applies NGS technology and metagenomic analysis to identify and characterize pathogens present in blood samples obtained from patient with febrile illnesses in Nigeria in order to improve differential diagnosis. METHODOLOGY: RNA was isolated from plasma samples obtained from patients with febrile illness. Nextera libraries were prepared and sequenced on the Illumina MiSeq and Hiseq/Novaseq next generation sequencing machines. Metagenomic analysis of the nucleotide sequences generated was done using viral-ngs 1.21.2 software executed on the cloud-based DNAnexus platform. Other pathogen taxa present in the samples were identified using Kraken by building a database that includes known human pathogens. To validate data and exclude false positives we used the negative control reads for various pathogens to set a threshold and further align reads to appropriate reference genomes using novoalign software. RESULTS: A total of 134 samples were sequenced and considered for this analysis. Lassa virus, Yellow fever virus, HIV and GB virus C were detected in 92(69%), 9 (7%), 1(1%) and 5(2%) of the samples respectively. Other pathogens

19 | P a g e detected are Plasmodium spps (10%) Leptospira interrogans (1%), Salmonella enterica (2%), Neisseria gonorrhoeae (2%), Mycobacterium tuberculosis (1.5%), Trypanosoma brucei (5%), Vibrio cholerae (1.5%), Cryptosporidium Parvum (1%) and Leishmania donovani (13%). NEXT STEPS: Future perspective will be to evaluate interactions between pathogens and link effect of coinfection on patient outcome.

H3Africa/GSK ADME: High throughput analysis of ADME pharmacogenomic variants at genomic and protein levels in African populations Houcemeddine Othman (1), Jorge da Rocha (1,2), on behalf of the H3A/GSK NCD Open Lab ADME Collaboration. (1) Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand (2) Division of Human Genetics, University of the Witwatersrand, Johannesburg. Pharmacogenomics is an active research field and availability of high quality whole genomes opens new avenues of research. The Absorption, Distribution, Metabolism, and Excretion (ADME) genes are involved in the in vivo processing of drugs and xenobiotics. Their function and genetic distribution significantly affects the pharmacogenomics properties in a population, which can have significant clinical implications. Africa has one of the most genetically diverse continental populations. Consequently, the ADME gene pool is affected by such diversity and there have been several studies reporting that the risk of adverse effects and pharmacological inefficiency in African populations differs substantially from non-African populationsfor. Previous studies reporting these effects have focussed on a limited number of genes and non-representative African populations. Herein, we present the H3Africa/GSK ADME project, aiming to explore pharmacogenomics variation of the African population at a large scale genomic level. The project, physically based at the Sydney Brenner Institute of Molecular Bioscience of the University of the Witwatersrand is the fruit of collaborative efforts between the H3Africa Consortium, with funding and support by GSK's Africa NCD Open Lab. High-coverage whole genome sequences (n=415)from at least eight sub-Saharan countries will be used in the study. The main objectives are to characterise rare and common pharmacogenomic variation in ADME genes in African populations and to investigate the functional effect of the identified variants in these populations. For such ends, four working groups were assigned to Genomic Mining, Copy Number variation (CNV) and Indel analysis, Protein Modelling/Structural Analysis and Pathway Analysis. In addition, the H3Africa/GSK ADME project aims to establish a substantial network in pharmacogenomics in term of capacity building and academic research at the continental and international levels.

Prevalence and characterization of haemophilus influenzae in the nasopharynx of young children, South Africa Authors: F. Patel (1)*, A.B. Brueggemann (7), M. Jansen van Rensburg (7) , H.J Zar (2,3,4), M.P. Nicol (1,5,6), L. Ah Tow (1)* (1) Division of Medical Microbiology, Department of Pathology, University of Cape Town, South Africa (2) Department of Paediatrics and Child Health, University of Cape Town, South Africa (3) Red Cross War memorial Children’s Hospital, Cape Town, South Africa (4) MRC Unit on Child and Adolescent Health, University of Cape Town, South Africa (5) Institute of infectious Disease and Molecular Medicine, faculty of Health Sciences, University of Cape Town, South Africa (6) National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa (7) Division of Infectious Disease, Department of Medicine, Imperial College, London BACKGROUND: Haemophilus influenzae, a coloniser of the nasopharynx (NP), is capable of causing infections such as otitis media, pneumonia and meningitis in young children. H. influenzae may be encapsulated (serotypes a-f) or unencapsulated (non-typeable, NTHi). It is unknown whether children are colonized by a single strain, or sequentially by multiple strains of H. influenzae. We investigated the longitudinal changes in the prevalence and diversity of H. influenzae in the nasopharynx of healthy infants using phenotypic and whole genome sequencing (WGS) data. METHODS: We included 137 children participating in a birth cohort, in Cape Town, South Africa (Drakenstein Child Health Study) between 2012 and 2013. Nasopharyngeal swabs were collected at birth and fortnightly thereafter for the first year of life, with additional sampling at 18 and 24 months. H. influenzae isolates were confirmed with molecular identification. Molecular typing was performed to classify isolates as one of six serotypes or non typeable. WGS was performed on the Illumina HiSeq platform. Genotypes were assigned using MLST and clonal complex data.

20 | P a g e

RESULTS: A total of 3616 nasopharyngeal samples were collected. None of the children were colonised at birth. H. influenzae prevalence at 2 weeks of age was 1.9% (2/106), reaching a peak of 54.5% (72/132) at 24 weeks of age. NTHi accounted for 92.4% (1282/1386), with serotypeable 7.5% (104/1386) and cap-deficient variants 0.1% (2/1386) accounting for the remainder. Serotype a,b,c,e and f accounted for 0.2%, 1.95%, 1.4%, 1.8% and 1.95% respectively. At the species level, a total of 332 acquisitions were seen in the first year of life. Recurrent episodes of colonisation were observed; mean first colonisation duration was 12 weeks. At the genotype level (using MLST and clonal complex data), there were 727 acquisitions and mean first colonisation duration was 7 weeks. CONCLUSION: NTHi accounted for the vast majority of H. influenzae isolates in this cohort. Incorporation of genotype data allowed us to obtain a more accurate estimate of number of acquisitions and carriage duration. Carriage with H. influenzae in infancy is more dynamic than previously appreciated.

Bioinformatics analysis of nicotinic acetylcholine receptor subunit α 8 (nAchra8) protein evolution in different higher and lower organisms. Medhat Radi (1), Ahmed M. Alzohiry Othman M. Othman (3), Elshiekh A. Ali (1), Aboghalia H Ahmed (4) (1) Pest physiology department Plant Protection Research institute, Dokki, Egypt (2) Faculty of Agricultural, Zagazig University, Zagazig, Egypt (3) Cell biology department, National Research center, Giza, Egypt (4) Faculty of science, Suez Canal University. Ismailia, Egypt Nicotinic acetylcholine receptors plays an essential roles in cognitive processes in higher organisms (e.g. human and mouse) and in lower organisms (e.g. insects). Nicotinic acetylcholine receptors (nAChRs) are member of prototypical cys-loop ligand-gated ion channel (LGIC) superfamily. During cell signaling, nAChRs mediates the fast actions of acetylcholine (ACh) at synapses. BLASTN and BLASTP search revealed the existence of nAChRα8 subunits in the gene and its protein in different organisms, but not limited to, human, mouse, rat, monkey, dolphin, zebra fish, pigeon, chicken, Asian honey bee, fruit fly, silk worm and threadworm similar to the honey bee nAChRα8 subunit gene and protein. The multiple sequence alignment (MSA) between all sequences was performed using Clustal omega with default setting. A phylogenetic tree was constructed by using jalview Neighbor joining algorithm. Studied sequences showed a significant degree of similarity which confirming their orthology. Further, investigations will be performed for nAChRα8 molecular modeling and docking.

IgG3 Allelic Variation Impacts Neutralization Potency and Fc Effector Function of an HIV V2-Specific Broadly Neutralizing Antibody Simone I. Richardson* (1,2), Bronwen E. Lambson (1,2), Andrew R. Crowley (3), Arman Bashirova (4,5), Cathrine Scheepers (1,2), Nigel Garrett (6,7), Salim Abdool Karim (6), Nonhlanhla N. Mkhize (1,2), Mary Carrington (4,5), Margaret E. Ackerman (3), Penny L. Moore (1,2,6), Lynn Morris * (1,2,6) (1) Centre for HIV and STI’s, National Institute for Communicable Diseases, Johannesburg, Gauteng, 2131, South Africa. (2) Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, 2193, South Africa. (3) Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, 03755, USA. (4) Ragon Institute of Massachusetts General Hospital, MIT, and Harvard University, Boston, Massachusetts 02129, USA. (5) Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702, USA. (6) Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, KwaZulu-Natal, 4013, South Africa. (7) Department of Public Health Medicine, School of Nursing and Public Health, University of KwaZulu- Natal, Durban, 4013, South Africa. IgG3 antibodies are associated with potent Fc effector function, which contributes to vaccine efficacy and HIV control. In an HIV-infected individual, CAP256, persistently high levels of plasma IgG3 mediated both broad neutralizing activity and Fc function. Sequencing of germline DNA and antibodies isolated from this donor revealed a novel IGHG3 allele (named IGHG3*01m) and long-lived IGHG3*17 allele. These IgG3 allelic variants of V2 broadly neutralizing antibody (bNAb) CAP256-VRC26.25 showed significant differences between them in their ability to mediate ADCC. Sequence analysis revealed that IgG3*17 has a lysine at position 392 that abrogates a potential N- linked glycan (PNG) motif present in the novel allele. Mutation of the lysine to an asparagine to match IgG3*01m restored ADCC activity. Neutralization potency was also significantly higher for IgG3 bNAbs with IgG3*01m showing increased potency compared to IgG3*17. Hinge region switches revealed this was largely a result of increased hinge

21 | P a g e length of IgG3*01m. Future directions include the assessment of mutations and long hinges to improve the functional activity of CAP256-VRC26.25 in humanised mice. These data indicate the functional relevance of allelic variation in the constant region which can be exploited for passive immunity.

Multidisciplinary investigation of rare genetic diseases in Tunisia Lilia Romdhane (1, 2), Mezzi, Nessrine (1), Abdelhak, Sonia (1) on behalf of the Laboratory of Biomedical Genomics and Oncogenetics and Collaborators (1) Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, 1002 Tunis Belvédère, Tunisia (2) Department of Biology, Faculty of Science of Bizerte, Université Tunis Carthage, 7021 Jarzouna, Tunisia North African populations constitute a large and heterogeneous group generated as a consequence of the admixture with many other Mediterranean, African and Middle Eastern populations throughout history. The population structure is characterized by a high rate of endogamous and consanguineous marriages; this cultural trait is shared with all the other countries in the region (i.e. North Africa and Middle East). The consequence of the particular familial and population structure is an increase in the prevalence of genetic diseases. During the last years, Tunisia, as other North African countries, is undergoing an epidemiological transition with an increase of the prevalence of non-communicable diseases. Despite educational, demographic and behavioral changes that have taken place during the last decades, endogamy still exists and consequently there is an increase in the frequency of genetic diseases. In order to assess the burden of these disorders, we have performed a systematic manual text mining of available data in the literature, including grey literature. More than 500 diseases of genetic origin have been identified of which more than 60 % are autosomal recessive. The most frequent disease set encompasses congenital malformations, deformations and chromosomal abnormalities (26%) of the genetic diseases followed by the endocrine, nutritional and metabolic diseases (24%) and diseases of the nervous system (18%). Approximately, half of the identified genetic diseases have not been investigated at the molecular level. Among the diseases with known molecular etiology, at least one founder mutation in one gene has been reported in addition to allelic and genetic heterogeneity. The health consequences of consanguinity include not only an increased risk of the expression of autosomal recessive diseases but also the co-occurrence of two or more genetic diseases and particular phenotypic expressions. More than 80% of the diseases could be considered as ultra-rare, as they affect less than one per 100.000 individuals. Consequently, diagnosis of these diseases is particularly challenging, taking into account their rarity and clinical and genetic heterogeneity. Using Next Generation Sequencing (NGS) allowed us to identify the mutation spectrum of several rare diseases in the Tunisian population, including patients with atypical ultra-rare phenotypes. The affected families benefitted from early molecular diagnosis, genetic counseling and prenatal diagnosis. NGS, in particular Whole exome sequencing (WES) in consanguineous families is becoming a very promising cost effective tool for disease gene identification and is having a dual role in diagnosis and research. Investigation of consanguineous populations gives also a unique opportunity to better evaluate the impact of consanguinity on the genome dynamic and on health. Indeed, it is questionable that consanguinity could lead only to negative effects and should have been culturally favored for some beneficial reasons.

MultiOmeSEQ: A suite of tools for integrated analysis of multi-level omics datasets Alfred Ssekagiri (1), Daudi Jjingo (2) (1) Department of Medical Microbiology, School of Biological Sciences, Makerere University, Uganda (2) Department of Information Technology, School of Computing Sciences, Makerere University, Uganda INTRODUCTION: Despite the potential of microbiomes in understanding health and disease, less has been done towards multi-omics level studying of microbiomes in relation to deadly diseases. Analysis of single-omic datasets for example metagenomics focuses on structure and functional profiles of microbial communities. This approach does not tackle interactions amongst the different entities of the microbiome. The aim of this project is to develop tools for integrative analysis of multi-omics data. METHODS:This project will employ genomic techniques to generate multi-omics high-throughput data including metagenomics and metatranscriptomics. Methods for integrative analysis of these data will be formulated using statistical models and tools developed to implement these methods. This will potentially reveal the integrative power of multi-omics analyses and provide a comparative platform with single-omic studying of microbial communities. TESTING AND VALIDATION: As a use-case, the implemented methods and tools will be used for studying microbial evolution and its role in tuberculosis pathogenicity. In addition to achieving objectives of this project, the designed methods and tools will be generally applicable to the field of microbial ecology and thus contribute to the continued understanding health and disease.

22 | P a g e

Minimum Information Required Research Reporting Guidelines - Case Studies from H3Africa Judit Kumuthini (1), Lyndon Zass (1), Melek Chaouch (6), Michael Thompson (7), Paul Olowoyo (2), Mamana Mbiyavanga (3), Katherine Johnston (3), Faniyan Moyinoluwalogo (4), Gordon Wells (1), Christiaan van Woerden (3), Andrew J. Mallett (5), Chirag Patel (5), Mayowa Owolabi (4), Nicola J. Mulder (3) (1) Centre for Proteomic and Genomic Research, South Africa (2) Ido-Ekiti/Afe Babalola University, Nigeria (3) University of Cape Town, South Africa (4) University of Ibadan, Nigeria (5) KidGen Renal Genetics Flagship, Australia (6) Institut Pasteur de Tunis, Tunis, Tunisia (7) National Institute of Mathematical Sciences, Kumasi, Ghana INTRODUCTION: The management and analyses of large datasets is one of the grand challenges of modern biomedical research. Large-scale data analytics have introduced new challenges to biomedical researchers, including the storage, management, and analyses of datasets. Standardising the methods in which clinical and research data are being collected, reported, managed and(or) stored can support the resolution of these challenges, by enhancing data compatibility, interoperability, reproducibility and re-use, and facilitating data sharing and collaboration. OBJECTIVES: The Human Heredity and Health in Africa’s Bioinformatics Network’s (H3ABioNet, www.h3abionet.org) (Mulder et al., 2016) Data & Standards work package aims to develop domain - specific data reporting guidelines, applicable to the H3Africa consortium, to specifically address the data management concerns in low-resource and low-income regions. Thus far, the project has targeted two domains that address global health concerns – stroke and kidney disease research. METHODS: To develop the reporting guidelines, a list of reporting recommendations was proposed based on the review of existing resources, including data collection measures on PhenX Toolkit, and experimental reporting guidelines on FAIRsharing. These recommendations were also harmonised with the H3Africa 2

Standard Case Report Form (CRF) Version 1.1. The recommendations were then reviewed by a broad range of domain researchers and clinicians, using anonymous online surveys, constructed to evaluate, and harmonize the recommendations, identify them as “essential” or “optional”, propose additional recommendations and remove any existing reporting inconsistencies. Once harmonized, the recommendations (henceforth referred to as elements) were manually defined using Zooma, and ontologies found using the BioPortal and Ontology Lookup Service (OLS) search engines. Associated eXtensible Markup Language (XML) schemas were developed for the reporting guideline, to carry all the data and metadata regarding the participant, experiment and study while maintaining the associations between them, allowing the exchange of biological and clinical data between dissimilar health information or research systems. RESULTS: The kidney disease online survey was completed by 46 international field-specialists; majority (57%) worked as dual clinician-researchers, majority had over 10 years’ experience in the field (78%), and majority was based in Australia (35%), followed by Africa (33%) and North America (22%). The stroke online survey was completed by 20 international stroke-specialists, majority were based in Africa (50%), followed by America (20%) and Europe (20%), majority (80%) were working as dual clinician- researchers and majority had over 10 years’ experience in the field (70%). The quintessential information reported using these standards is separated into three fields; participant-level, study-level and experiment-level information. Participant-level information include Demographics, Lifestyle Factors, Anthropometrics, Blood Pressure, Adverse Drug Reactions, and more. Study-level information include Study ID, Research Institute and Study Design. Experiment-level information include Biopecimen Type, Instrumentation employed, Sample Management Protocol, Quality Control Protocol and more. NEXT STEPS: The reporting guidelines are designed for use by research clinicians and healthcare workers, researchers, data managers and bioinformaticians involved in stroke or kidney disease research. The reporting guidelines go beyond listing “minimum required” data elements and aim to provide a comprehensive data dictionary, with standardized response options, which can be adapted for broad use. To promote the adoption of the reporting guidelines, we hope to employ the reporting guidelines within our own consortia studies, and advocate use on an international platform. Ultimately, the reporting guidelines have the potential to support both the H3Africa community as well as the stroke and kidney disease research communities at large with current and future research..

23 | P a g e

BIOGRAPHIES

FELLOWS Mr. Elvis Twumasi Aboagye [email protected] Doctoral degree student University of Ghana, Ghana; University of Cape Town, Soth Africa, Aboagye, Elvis Twumasi is a Ph.D. student at the University of Ghana and holds a thesis completion fellowship at the University of Cape Town. He is working on Hearing Impairment Genetic Studies (HI-GENES) in Africa Project. This project seeks to explore functional genomics and African genome diversity to elucidate specific markers linked to human hearing disorders. The goal is to establish a causal link between population-specific genetic variations and epigenetic modifications/dysregulation, to disease etiology or susceptibility. At the West African Centre for Cell Biology of Infectious Pathogens (University of Ghana) and Division of Human Genetics (University of Cape Town), we are focused on elucidating population-specific genetic marker for segregating early on-set of autosomal recessive non- syndromic hearing impairment (ARNSHI) in Africa. The target is to create and design a molecular diagnostic tool for newborn screening in Africa. Future investigation will explore 1) the use of computational algorithms to correct varied cellular epigenetic dysregulation, 2) epi-transcriptomics and disease/disorders, and 3) single-cell methods that allow description of single-cell resolution of DNA modifications Ms. Ester Acen [email protected] Doctoral degree student Makerere University, Uganda I am a Biomedical scientist with a masters in Biomedical Lab Sciences and management. I am currently a Ph.D. student in the department of microbiology College of Health Sciences at Makerere University. Ms. Fehintola Ajogbasile [email protected] Doctoral degree student Redeemer's University, African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Nigeria My name is Ajogbasile Fehintola Victoria, a Ph.D. student in molecular biology and genomics at the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University, Nigeria. My research focus is on the genetic diversity and molecular surveillance of antimalarial resistance of Plasmodium falciparum in Nigeria. I also have an interest in the genetic diversity of other pathogens transmitted by mosquitoes. Dr. Monia Ardhaoui [email protected] Postdoctoral fellow Institut Pasteur de Tunis, Tunisia Monia Ardhaoui is a postdoctoral researcher at the Laboratory of Molecular Epidemiology and Experimental Pathology at the Institut Pasteur de Tunis. She is also working as project manager of the Clinical Investigation Center at this Institute. Monia received her Ph.D. and MSc degrees from the High Institute of Biotechnology and Faculty of Pharmacy at Monastir University, Tunisia, respectively. She has multidisciplinary research skills on Molecular Biology, Biostatistics, and Bioinformatics. Her research interests include but are not limited to the area of infectious diseases and epidemiology. For her master project, she has worked on the detection and genotyping of rotaviruses in children with Intestinal Invagination. She acquired skills in Molecular Biology and Biostatistics. During her Ph.D. she conducted the first national epidemiological study in Tunisia, funded by the African Bank of Development, which was focused on HPV cervix infection prevalence and genotype distribution in a large sample of Tunisian women. In addition, she has got a Yersin and Calmette Fellowship of the network of Pasteur Institutes to attend a training at the Center of Excellence in Bioinformatics (CEBio) of the FIOCRUZ René Rachou institute in Belo Horizonte, Minas Gerais- Brazil, where she developed HPV genotyping using NGS. Her research outcomes include articles in peer-reviewed, indexed journals and numerous communications in international conferences. Her results on the prevalence of HPV infection and NGS defined genotypes are used to inform policy as regards the adoption of HPV vaccine strategies.

Ms. Maroua Boujemâa [email protected] Doctoral degree student

24 | P a g e

University of Tunis El Manar, Pasteur Institute of Tunis, LR16IPT05 Laboratory of Biomedical Genomics and Oncogenetics,1002, Tunis, Tunisia Ph.D. student at Laboratory of Biomedical Genomics and Oncogenetics in Pasteur Institute of Tunis. Working on the genetic basis of breast cancer in Tunisian population. Graduated with a Master's degree in biomedical sciences “with highest honour” from Higher School of Health Sciences and Techniques of Tunis. Member of H3ABioNet Pasteur Institute of Tunis-node. Dr. Jean-Tristan Brandenburg [email protected] Postdoctoral fellow Sydney Brenner Institute for Molecular Bioscience - Wits University, France I am a postdoctoral researcher at Sydney Brenner Institute for Molecular Bioscience - Wits University. My main researches are concentrated on the analysis of kidney diseases (CKD) in epidemiological and genome-wide analysis. Along with my colleagues, we were analyzing the prevalence of CKD in different African site. Furthermore, with Genome-Wide Association approach and genetics data, we research some locus link with phenotype as CKD. Dr. Melek Chaouch [email protected] Postdoctoral fellow Institut Pasteur de Tunis, Tunisia, Tunisia I entered the Pasteur Institute in 2006 as a graduating engineer from The National Agronomic Institute of Tunisia to fulfill my graduate internship. Fascinated by the scientific research, advances in molecular biology, the available technologies, and devices that I have seen in that honorable institution, I decided to pursue my graduate studies Masters (Graduation -2008) and Ph.D. research (Graduation -2014) within the same department and institution. Throughout these years I have gained a large experience in the fields of parasitology, molecular biology and bioinformatics, and I have developed a heavy sense of analysis and significant research potential. Post-doc Researcher 2015/2016 Postdoctoral researcher at Institut Pasteur de Tunis, Medical Parasitology Biotechnology and Molecules Laboratory, as part of the project financed by the World Health Organization (EMRO TDR-), entitled “Development and evaluation of a Loop-mediated Isothermal Amplification method for the diagnosis of Old world Leishmania in Tunisia “. Post-doc Researcher August 2016 Postdoctoral Fellow at Institut Pasteur de Tunis, Laboratory of BioInformatics, bioMathematics, and bioStatistics (BIMS). H3ABioNet node ambassador and active member of projects within different work packages. Mr. Hamza Dallali [email protected] Doctoral degree student Pasteur Institute of Tunis, Tunisia Hamza Dallali is a Ph.D. student in the final year of the thesis in the Laboratory of Biomedical Genomics and Oncogenetics in the Pasteur Institute of Tunis under the supervision of Pr. Sonia ABDELHAK and Dr. Rym Kefi. He started his thesis entitled: “Investigation of monogenic and multifactorial forms of diabetes and its complications in the Tunisian population” upon graduation as an engineer in Industrial Biology from the National Institute of Applied Sciences and Technology in 2015. During his thesis, he participated in the MEDIGENE project investigating the genetic and environmental factors of metabolic syndrome in the Mediterranean populations through the design and the statistical analyses of association studies. In addition, he is a member of the H3ABioNet Tunisian node, and he contributed to the analysis of Next Generation Sequencing (NGS) data for the different projects in the laboratory. Moreover, he got in touch with the use of NGS for the molecular investigation of monogenic forms of diabetes. Indeed, he carried out a six-month internship in the diabetes unit at the Mendel Institute (Rome, Italy), which allowed him to experience library preparation for an NGS panel as well as the functional annotation of genetic variants. This latter work is actually in the press. Currently, he is writing his thesis manuscript in order to defend it during this year. Ms. Sara El Jadid [email protected] Doctoral degree student National School of Applied Sciences of Tangier, Abdelmalek Essaadi University, Morocco Sara El Jadid ([email protected]) is a Ph.D. student working in Bioinformatics in the field of analyzing Proteomics data. Prior to beginning the Ph.D. program, Sara has completed her Master's degree with honors in bioinformatics in the National School of Applied Science of Tangier-Morocco. She had an internship in INRA in Paris (France) for her Master's thesis where she developed new features for MassChroQ (a tool performing quantification of proteins). She is a training assistant for the CODATA-RDA School for research data science. After

25 | P a g e being a student in the event, she was invited in Trieste, Sao Paulo, and Kigali to act as a mentor to provide assistant and mentorship to participants. She is preparing herself to become a researcher involved in high technology programs in bioinformatics and she has a special interest in some key areas of research, such as proteomics, drug discoveries, rare diseases, and cancer. Mr. Cherif Ben-Hamda [email protected] Doctoral degree student Tunis, Tunisia He is a bioinformatician who is currently a member of the Laboratory of Bioinformatics, in Institut Pasteur de Tunis. He is a part of the functional genomics team within its affiliated lab. Cherif has a background in biology, his main interest includes gene expression profile analysis, regulatory genomics, functional genomics, gene/protein interaction networks, metagenomics, new genome assembly, and web tools development. After obtaining his master degree in Biochemistry and Biotechnology, he started his Ph.D. in Bioinformatics in 2014, in the frame of H3ABioNet project. During which, he worked on large scale OMICS data analysis and identification of candidate genes involved in a particular phenotype. Cherif has been a bioinformatics lecturer in several national and international courses. He co-authored several articles and book chapter during his Ph.D. and will defend his thesis project by February 2018. Ms. Mariem Hanachi [email protected] Doctoral degree student Institute Pasteur of Tunis, College of Science of Bizerte, Tunisia After obtaining my first master's degree in "Infectious Diseases, Contagion and Prevention" at the Marseille Faculty of Medicine, I pursued a second master's degree in "Human Genetics and Animal Models". During these masters, I followed internships in which I focused on the study of pathogens such as amoebae, bacteria, and the parasite Leishmania. I was thus introduced to different cell culture and molecular biology techniques. Interested in the field of Bioinformatics, I am currently pursuing a thesis at the Pasteur Institute of Tunis in the "Bioinformatics, Biostatistics and Biomathematics" laboratory under the supervision of Dr. Oussema Souiai and Dr. Alia BenKahla. My thesis subject mainly concerns the study of the intestinal microbiota and more precisely the study of phages. Dr. Eric Katagirya [email protected] Makerere University, Uganda Medical doctor and Biomedical scientist with in-depth training in clinical microbiology and genetics/genomics analysis.

Mr. Ayoub Ksouri [email protected] Doctoral degree student Institute Pasteur of Tunis, Tunisia Ayoub Ksouri is P.hD student from Tunisia, graduated in biotechnology (bachelor's degree) and microbiology (Master degree), and currently, he finished his Ph.D. project (to be defended before 2019) related to immune- bioinformatics as part of the H3ABioNet project phase 1 (Tunisian node). During the last 5 years, he acquired valuable skills with data sequence analysis of DNA and proteins. He developed pipelines to achieve sequence signatures, structure patterns as well as 3D function-structure relationships. Within Bio-Informatic, biomathematics, and biostatistics (BIMS) Lab research group, he is regularly performing High throughput data analysis tasks of Chip- Seq, RNA-Seq, metagenomics, gene variants associated with disease and variant calling, in the frame of H3ABioNet Tunisian node. In addition, I am an active collaborator with Tunisian H3ABioNet Node as a researcher working on a project in structural bioinformatics and as teaching lecturer for the annually held summer course (IBT). Along with his Ph.D. training, he participated in several local and international courses/workshops. I also had opportunities to participate as a speaker on helpful tools and pipelines for High throughput data analysis (NGS, GWAS, ...) and lecturer for training computer languages (R, Python, and Perl).

Mr. Foued Maaoui [email protected] Virtual University of Tunis, Tunisia; Pasteur Institute of Tunis, Tunisia Researcher in Education Sciences, I work in the field of health education. Our goal is the innovation of emancipatory educational interventions for infectious and noncommunicable diseases.

26 | P a g e

Ms. Noluthando Manyisa [email protected] Doctoral degree student University of Cape Town, South Africa Ph.D. Candidate at the Division of Human Genetics, University of Cape Town. My research focuses on hearing impairment in African populations and I am a part of the HIGenes project

Ms. Monica Mbabazi [email protected] Makerere University, Uganda Studied in Bweranyangi Girls'School, Studied at Mbarara University, a bachelor at Kyambogo University. Currently pursuing a masters at Makerere University. Look forward to being one of the greatest scientists in Africa.

Mrs. Najah Mighri [email protected] Doctoral degree student Institut Pasteur de Tunis, University of Tunis ElManar, Tunisia Ph.D. Student at the laboratory of Biomedical Genomics and Oncogenetics in Institut Pasteur de Tunis. My research project aims to investigate the clinico-epidemiological profile and genetic features of Breast cancer in Tunisian population. Graduated with a professional Master's degree in Biotechnology and industrial development from the Higher Institute of Biotechnology, Sidi Thabet, Tunisia in 2012 and with a research master’s Degree in molecular biology from the same institute in 2015. Mr. Savannah Mwesigwa [email protected] Doctoral degree student Makerere University, Uganda Savannah Mwesigwa has been supported by the CAfGEN project at Baylor College of Medicine (BCM) since June 1st, 2014. He is a doctoral student from the College of Health Sciences, Department of Medical Microbiology, Makerere University, Kampala, Uganda. During his laboratory rotation with Dr. Neil Hanchard at the USDA/ARS Children's Nutrition Research Center, BCM, he utilized whole exome sequencing (WES) data to investigate hyperhemolysis syndrome in sickle cell patients receiving recurrent transfusions. The goal of this project is to identify novel genes that may play a role in this condition. He carried out the data processing and bioinformatics filtering where he identified a loss-of-function variant in the MBL2 gene that may be a possible contributor to this condition. For this, he was given the top abstract award for the 2016 AABB annual meeting and has prepared a draft manuscript for publication. This rotation provided him an excellent opportunity to develop the necessary bioinformatics skill-set that he is currently utilizing in his doctoral research project where he is looking into off- target reads from WES data. So far, he has extracted viral, mitochondrial, and splice-sites DNA sequence reads and hopes to identify key genetic differences that may be associated with HIV disease progression in pediatric African populations.

Ms. Margaret Nabatanzi [email protected] Doctoral degree student Rhodes University, South Africa Margaret Nabatanzi is a Ph.D. student in Bioinformatics at Rhodes University, South Africa. She completed a master’s degree in Bioinformatics from Rhodes University, and a bachelor’s degree in Computer Science from Makerere University, Uganda. Her current work involves further development of the PRIMO pipeline to model protein complexes. For her MSc. she worked on a web application that employs artificial neural networks to predict HIV drug resistance. For her Ph.D. project, Margaret plans to continue working on improving methods for predicting drug resistance using machine learning in single nucleotide polymorphisms (SNPs) analysis. Outside her current Ph.D. work Margaret is interested in medical statistics, big data analytics, machine learning, and artificial intelligence, which together with bioinformatics she intends to pursue as part of her life-long career plan. Ms. Rose Nabatanzi [email protected] Doctoral degree student

27 | P a g e

Makerere University College of Health Sciences, Uganda I am a junior scientist at Makerere University College of Health Sciences with an interest in the immunology of infectious diseases in particular HIV and its co-infections. I am a second year Ph.D. student at Makerere University, College of Health Sciences. I have bachelor’s degree in biomedical laboratory technology and a Master of science degree in immunology and Clinical Microbiology both from Makerere University. I have extensive laboratory experience doing hands-on laboratory bench work at various specialized research centres including the Uganda Virus Research Institute, Joint Clinical Research Centre and currently MakCHS. My research interests are in conducting translational research in infectious diseases in particular HIV/AIDS and its co-infections. My current research as a Ph.D. fellow is looking at the recovery of the innate immune responses after long term Antiretroviral therapy in an African cohort. I am focusing on utilizing my excellent laboratory skills and experience to answer questions relevant to improve patient care and address challenges related to global health in Africa. My long-term goal is to become an internationally recognized independent researcher in academia.

Ms. Careen Naitore [email protected] Master’s degree student Jomo Kenyatta University of Agriculture and technology Msc student taking bioinformatics and molecular biology Research title is “miRNA transcriptome in tsetse”Skills : Bioinformaatics skills; Transcriptomics analysis functional genomics analysis, stucture analysis, differential expression analysis

Mr. Chukwuemeka Nwankwo [email protected] Doctoral degree student Redeemer's University, Nigeria Chukwuemeka has over 30 months of post-graduate teaching and research experience in microbiology. In his BSc thesis, he elucidated the microbial content in cattle egret droppings gotten from a contaminated site in Redemption Camp, Mowe, Ogun State, and discovered many harmful microorganisms including Escherichia coli and Salmonella typhii. His MSc dissertation was titled ‘Antimicrobial and Spectroscopic analyses of Cola millenii K schum’ in which he investigated claims about the medicinal plant. Spectroscopic analyses revealed the presence of several bioactive compounds. His Ph.D. research is on Schiff Bases and their antibiofilm activities using Pseudomonas aeruginosa strain PA01. He is a JWARG certified malaria microscopist and CITI certified in Conflicts of Interest and Health Information Privacy and Security.

Mrs. Judith Oguzie [email protected] Doctoral degree student Redeemer's University, African Centre of Excellence for Genomics of Infectious Diseases, Nigeria Judith Uche Oguzie is a Doctor of Veterinary Medicine (University of Maiduguri)Doctro with an MSc in Medical Microbiology and currently a Ph.D. student (Molecular Biology and Genomics at the African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer's University. Her research interests include the prevention, characterization, and control of zoonotic pathogenic infection in vectors/animal reservoirs and humans as well as applying molecular tools such as Polymerase Chain Reaction and Next generation sequencing in understanding pathogens responsible for infectious disease outbreaks.

Dr. Houcemeddine Othman [email protected] Postdoctoral fellow Sydney Brenner Institute for Molecular Bioscience - University of the Witwatersrand I am a postdoctoral researcher at Sydney Brenner Institute for Molecular Bioscience - Wits University. My main researches are concentrated on the structure-activity relationship of proteins using in silico approach. Along with my colleagues, we are developing bioinformatics tools to understand the impact of mutations on the structures of proteins involved in drug metabolism using multidisciplinary approaches.

Ms. Fadheela Patel [email protected] Doctoral degree student University of Cape Town, South Africa

28 | P a g e

I am a Ph.D. student in the Medical Microbiology Department at the University of Cape Town.

Mr. Medhat Radi [email protected] Doctoral degree student Plant protection research institute, Egypt Medhat Radi Abdelrahman is assistant research in plant protection research institute. Also a Ph.D. student at Suez Canal University. His Ph.D. work for two years focus specifically on honey bee memory genes and learning behavior. Medhat got a master degree in molecular genetics from Zagazig University. Furthermore, he is a TOT in bioinformatics belongs to The Egyptian center of bioinformatics and genomics. He interested in learning and expand his boundaries in many science branches like molecular genetics, microbiology, bioinformatics and any other related branches also teaching and spread all knowledge in his bag to his colleagues and students so he is a leader for scientific group and a coordinator of non- profit group known as "preparing of Egyptian scientist project" finally, Medhat loves reading, drawing and traveling

Dr. Simone Richardson [email protected] Postdoctoral fellow National Institute for Communicable Diseases, South Africa I am a postdoctoral fellow at the National Institute for Communicable Diseases in Lynn Morris group. I am interested in the functional relevance of novel antibody alleles with particular relevance to the Fc region.

Dr. Lilia Romdhane [email protected] Institut Pasteur de Tunis, Tunisia; Faculté des Sciences de Bizerte, Tunisia I am an assistant professor at the Department of Life Sciences at the Faculty of Sciences of Bizerte. I teach bioinformatics and genetics to undergraduate students. I am also a research associate at the Laboratory of Biomedical Genomics and Oncogenetics at the Pasteur Institute of Tunis. My research activities focus on rare and ultra-rare genetic diseases in order to establish their spectrum in the Tunisian population, their molecular bases and the impact of the consanguinity on their occurrence and on the genome structure through textual mining, high-throughput genotyping and sequencing data analyses.

Mr. Alfred Ssekagiri [email protected] Doctoral degree student Makerere University, Uganda Alfred Ssekagiri is a first year Ph.D. candidate at the University of Makerere, Uganda in the Department of Medical Microbiology under the supervision of Dr. Daudi Jjingo and Dr. David Kateete. His research interests are in the area of microbial informatics, with interest in developing tools for analysis of microbial communities and relationship between the microbiome, antimicrobial resistance, health, and disease. He obtained his B.Sc. from Makerere University where he studied Mathematics, physics with education. He later joined African Institute for Mathematical Sciences where he obtained M.sc. in Applied mathematics. Alfred received an M.Sc. in Bioinformatics from the University of Glasgow where he developed an R package for statistical analysis of microbial communities in an environmental context. He has participated as H3ABioNet bioinformatics associate at Uganda Virus Research Institute, co-facilitated bioinformatics training hosted at the institute and East African Network for Bioinformatics Training (EANBiT).

Mr. Lyndon Zass [email protected] Center for Proteomic and Genomic Research, South Africa I am a junior bioinformaticist at the Centre of Proteomic and Genomic Research (CPGR) H3ABioNet node. I graduated from Stellenbosch University with a Masters degree in Human Genetics in 2017. Currently, I am working under the supervision of Dr. Judit Kumuthini, where I function as the co-lead of the Helpdesk management and development project and am involved in a number of H3ABioNet-related pharmacogenomics, data management, data standardization, and training projects.

29 | P a g e

TRAINERS

Sonia Abdelhak [email protected] Institut Pasteur de Tunis Dr Sonia Abdelhak DSc, PhD, is head of the Research Laboratory on Biomedical Genomics and Oncogenetics at Institut Pasteur de Tunis. She is mainly involved in the study of the molecular basis of inherited rare disorders in endogamous populations. Dr Abdelhak is author of more than 170 scientific publications. She is also involved in R&I training activities and capacity building in human molecular genetics, genomics and bioinformatics. Dr Abdelhak acts as an independent expert for national and international institutions (Tunisian Ministry of Higher Education and Scientific Research, the EU for European Research framework programme…). She is currently involved in the EU-H2020 project “Ingenious Science shops to promote Participatory Innovation, Research and Equity in Science” http://www.inspiresproject.eu/. Since 2011, Dr Abdelhak is the General Secretary and founding member of an NGO, Association la Recherche en Action (React-tn) www.react.org.tn.

Mr. Paballo Chauke [email protected] University of Cape Town, South Africa, South Africa Paballo Chauke, currently Training and Outreach Coordinator for H3ABIONET- a Pan-African Bioinformatics Network for H3Africa, has an MSc in Biodiversity, Conservation and Management (BCM) from the School of Geography and Environment (SoGE) at the University of Oxford (Oriel College) in the United Kingdom. His MSc research was titled “Fighting the Good Fight: Green Violence and Anti-Poaching of Rhino in the Kruger National Park, South Africa”. Mr. Chauke also has two degrees from the University of Cape Town, an undergraduate degree with a triple major in Sociology, Environmental Geographical Sciences, and Xhosa Communication. He also holds an honours degree in Environmental Geographical Sciences from the same institution. He has a multi-trans and cross-disciplinary background and has a vast experience in research, coordination, facilitation, teaching, translation, supervision, mentoring and volunteering. He has a myriad of overlapping interests and skills/experience ranging from climate change, (sexual) health, poverty eradication, land restitution, nature conservation, and social justice just to name a few.

Kais Ghedira [email protected]

Amel Ghouila [email protected] Institut Pasteur de Tunis Amel Ghouila is a bioinformatician at Institut Pasteur de Tunis, where she works on the frame of H3ABionet. She has a background in computer sciences with a PhD in Bioinformatics from the LIRMM, Montpellier. Within H3ABioNet, she is involved in teaching activities, coordinates the sustainability and outreach and leads the Machine Learning group. Amel is an Open Science and Open Education advocate. She was nominated by Mozilla as one of “50 People Who Are Making the Internet a Better Place. She is the general secretary for the African Society of Bioinformatics and Computational Biology (ASBCB) and is a regional ambassador for the Technovation program: the global tech entrepreneurship for young girls.

Ikram Guizani [email protected] ; [email protected] Institut Pasteur de Tunis Ikram Guizani is expert in leishmaniasis research. She is holder of a PhD and a Doctorat d’Etat from Universities of Nice and Tunis El Manar, respectively. Throughout her career at the IPT, Ikram supervised more than 40 Post- doctoral, PhD and Master Students in Molecular biology and Genetics, Parasitology, Microbiology, Biochemistry, Bioinformatics and Genomics fields. She authors more than 50 publications and chapters, and 3 patents. She received different awards and grants from EU- programs, TDR, AUF, CRDF, Inst. Pasteur, PEER/NAS-USAID... She has a large professional service experience including membership to EU panels, TDR steering committees, TDR-STAC and management of international networks (eg SSI-TDR).

30 | P a g e

Yosr Hamdi [email protected] , [email protected] Institut Pasteur de Tunis Yosr Hamdi followed her graduate studies at Laval University, Quebec, Canada. She started in the field of human genetics with Pr. Alan Anderson who led her graduation project (2005) on the Human Genome Project. Then she focused her studies on the genetic component of breast cancer. She had a Master degree in Cellular & Molecular Biology at the faculty of Medicine, Laval University where she did bioinformatics studies on genes involved in oxidative stress and their association with breast cancer. She joined the Genomics center of the Hospital Center of Laval University, Quebec, Canada, where she obtained her PhD in Molecular Medicine. She identified two new loci 4q21 and 11q22, as associated with the overall breast cancer risk, and with the modification of breast cancer risk in BRCA1 mutation carriers, respectively. Combining genomics, cellular and molecular biology and bioinformatics, she continues the genetic and molecular investigations of breast cancer in African populations, as a part of her postdoctoral studies at Institut Pasteur de Tunis, Tunisia.

Rolanda Julius [email protected] University of Cape Town Rolanda Julius recently completed her PhD in Zoology with the University of Pretoria. She is a member of the South African Council for Natural Science Professions (SACNASP) and her research interests include zoonotic disease ecology, parasitology and molecular phylogenetics. She has experience in teaching molecular techniques, facilitating practical course components and as has been a tutor for several undergraduate modules in the natural sciences faculty. She has also co-supervised postgraduate honours and MSc degree studies. She is dedicated to promoting public health awareness and life science education.

Rym Kefi [email protected] , [email protected] Institut Pasteur de Tunis Dr Rym KEFI is a Senior Lecturer (PhD, Habilitation to Supervise Research) in Institut Pasteur in Tunis (IPT).Team leader in the Laboratory of Biomedical Genomics and Oncogenetics and responsible for the Genetic Typing Laboratory in IPT. She obtained a Master degree and a PhD at the University of the Mediterranean (Marseille- France). She joined in 2006 IPT. She is mainly involved in research on human genetic disorders, genetic diversity in North Africa and genetic typing in forensic. Rym KEFI is TWAS young affiliate, Global Young Academy member, laureate of the Next Einstein forum and young scientist member of the World Economic forum. Rym KEFI is also involved in training and teaching activities. She is an author/ co-author of more than 70 publications.

Ahmed Rebai [email protected] Center of Biotechnology of Sfax, Tunisia Pr Rebai get a PhD degree in statistical genetics in 1995 and he is currently director of the Laboratory of Molecular and Cellular Screening Processes at the Centre of Biotechnology of Sfax. and leads a research group in computational biology working on computational methods, tools and techniques for the analysis of genomics data and their applications to the diagnosis and prognosis of complex diseases. He published more than 200 journal articles, edited one book and filed three patents. Pr Rebai was awarded the National Medal of The Tunisian Republic in Science and Education in 2006.

Oussema Souai [email protected] IPT, Tunisia During my master thesis on Bioinformatics at the University of Provence, France, I retained the idea that I need to improve my skills in the field in my native country. For that, I contacted Dr. Alia Benkahla to be my co-supervisor (with Christine Brun) during my Ph.D. She was welcoming and we worked successfully on the prediction, inference, and analysis of host and pathogen interaction networks. After my thesis defense, I was engaged in 2 years contract as a post-doc fellow in the INRA, Versailles. During these 2 years, I focused on the annotation of phage proteins using hidden Markov models. During my second post-doc, in the CNRS, I worked on the analysis of RNAseq data and more specifically on the “Detection of generic differential RNA processing events from RNA-Seq data.

31 | P a g e

The latter post-doc position was in the Pasteur Institute of Tunis as RNA-seq analyst. We were particularly focusing on transcriptomic changes for public health issue diseases such as (Leishmaniosis, TB, Crohndiseases...) Finally, I was hired in Oct 2015 as an assistant professor in the Institut supéreur des technologies médicales de Tunis, where I'm a lecturer in Computational Biology and Biostatics. Simultaneously, I still conduct my research in microbiome, metagenome and RNAseq analysis in the IPT.

Sadri Znaidi [email protected] Institut Pasteur de Tunis Dr. Sadri ZNAIDI is a biochemist (B.Sc., M.Sc. from the Université de Sherbrooke, Canada) and molecular biologist (Ph.D., from the University of Montreal, Canada), with expertise in yeast genetics and functional genomics. He is currently a RIIP (Institut Pasteur International Network) Affiliate Program Fellow, with affiliations at the Institut Pasteur in Tunis and Paris. His current work focuses on the implementation of systems biology-oriented approaches to identify and characterize components of the biological circuitry involved in the interaction of fungal pathogens with the host environment.

32 | P a g e

ORGANIZING TEAM Michelle Skelton Prof Ahmed Rebai Project Manager/PI Centre of Biotechnology of Sfax H3Africa Administrative Co-ordinating Centre [email protected] (H3ACC) Department of Integrated Biomedical Sciences Amel Ghouila University of Cape Town Local Conference Organiser Tel: +27 (0) 21 650 1947 [email protected] Mobile: +27 (0) 82 810 3031 [email protected] Cherif Ben Hamda Local Conference Organiser Linda Dywili [email protected] H3ACC Administrative Assistant & Events Coordinator Cyrine Bouabid Tel:+27(0)216505307 Local Conference Organiser Mobile:+27(0)738686126 [email protected] [email protected] Hamza Dalleli Rolanda Julius Local Conference Organiser H3ACC Training Coordinator [email protected] Tel:+27(0)216505307 Mobile: +27(0)834899875 Kais Ghedira [email protected] Local Conference Organiser [email protected] Rosalyn Wamuyu H3Africa Grants Officer Maria Kabbage [email protected] Local Conference Organiser Tel: +254 20 806 0674 [email protected]

Confidence Mothiba Mariem Hannachi H3ACC IT Support Consultant Local Conference Organiser Faculty of Health Sciences [email protected] University of Cape Town [email protected] Maroua Boujemâa Local Conference Organiser Deidre Raubenheimer [email protected] UCT Bremner Building, Lower Campus, Rondebosch, 7700 Melek Chaouch Tel: +27 (021) 406 6167 Postdoctoral Fellow Email: [email protected] | www.uct- Institut Pasteur de Tunis cmc.co.za Address: 13, Place Pasteur-B.P 74 1002 Tunis Belvédère Sonia Abdelhak [email protected] Institut Pasteur de Tunis [email protected] 13, Place Pasteur 1002 BP74 Meriem Fassatoui Tunisia Local Conference Organiser [email protected] [email protected]/meriem.fassatoui [email protected] @outlook.fr

Alia BenKahla Monia Ardhaoui Laboratory of BioInformatics, bioMathematics and Local Conference Organiser bioStatistics (BIMS) [email protected] Institute Pasteur of Tunis E-mail: [email protected] Nadia Kheriji Local Conference Organiser [email protected]

33 | P a g e

Rym Ouni Olfa Mghirbi Local Conference Organiser Local Conference Organiser [email protected] [email protected] Yosr Hamdi Oussama Souiai Biomedical Genomics and Oncogenetics Local Conference Organiser Institute Pasteur of Tunis, Tunisia [email protected] [email protected]

Members H3Africa Education and Coordinated Training Working Group (ECTWG)

EMERGENCY NUMBERS Police: Ambulance Fire brigade 197 190 198

34 | P a g e

SITE MAP

35 | P a g e

NOTES

36 | P a g e