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South African National Bioinformatics Institute - Research Interests and Current Projects

 

Research at SANBI has set well recognised milestones in the field of computational biology. Our tools and techniques have not only been developed but also implemented across heterogenous domains of advanced research. Local and international efforts have driven our discoveries. Until recently, the core of SANBI’s research has focused upon gene expression biology.

Methods developed and applied at SANBI revolve around a greater understanding of the underlying causes of diseases. We approach the problem by comparison of genes, genomes and transcriptomes. We use computational gene expression biology to create novel biological insights and to provide biomarkers for experimental validation. We perform analysis of human genome variation, transcriptional diversity on both the expression and splicing level and the unravelling of transcriptional regulatory networks.

Dr Junaid Gamieldien 

The Knowledge Integration and Biomarker Discovery Group's core focus is the development of computational tools that improve the success rate of integrative ultra-high-throughput genomics experiments. The group's core project applies knowledge representation theory to produce a semantic database, called the BORG (BioOntological Relationship Graph). which assimilates millions of biological and biomedical facts into a large on-disk virtual 'mind map'. The project's initial focus was to develop querying facilities that enable researchers to perform large and complex in-silico experiments in exactly the way that they think about it, were it humanly possible to remember all the facts that are effectively the result of hundreds of thousands of functional, gene knockout, gene expression and disease association experiments. This focus has been further extended to using the existing knowledge in the database to identify causative mutations in in-house and collaborative clinically-targeted Next Generation Sequencing projects through the use of novel guilt-by-association and guilt-by-transitive-association strategies. The group is also working on several other clinical genomics projects including re-mining the plethora of genomics experimental data in public databases for simple diagnostic, prognostic and clinically informative biomarkers; and also in-silico drug lead discovery.

Current Projects

  • Semantic Integration of Biomedical Knowledge to Support In-Silico Discover

  • Next Generation Sequencing and Semantic Discovery for Personalised Genomic Medicine

  • Normalization and statistical methods for cross-platform expression array analysis

  • Graph theoretic methods for identifying functionally important proteins in protein interaction networks and their applications to cancer

  • Development of a simple artificial intelligence method to accurately subtype breast cancers based on gene expression barcodes

  • Massively-parallel computational identification of novel broad spectrum antivirals to combat coronavirus infection  


Professor Simon Travers

Prof Travers' research interests involve using computational approaches to study the molecular evolution of Human Immunodeficiency Virus (HIV).  His research focuses on understanding the mechanisms of how the virus evades various therapeutic interventions and how we can use computational tools to predict the likelihood of treatment failure in individuals about to start on antiretroviral drugs.  His other main research involves modelling the structure of carbohydrates bound to the surface of a HIV virion with a view to identifying novel therapeutic targets.

Current Projects

  • Seq2Res: A computational pipeline for the implementation of high-throughput, cost-effective HIV drug resistance testing.
  • Exploring the application of next-generation sequencing technologies to HIV drug resistance testing.

  • Biologically relevant  Sequence Alignment on Graphics Processing Units

  • Elucidating the structural conformation of the epitopes of glycan-binding agents that play a role in HIV neutralization.

  • Uncovering HIV sexual transmission networks in Karonga District, Malawi.

  • Characterizing the prevalence and mode of CXCR4-usage in HIV-1 subtype C

 

Professor Alan Christoffels 

My bioinformatics laboratory studies host-pathogen interactions with a view to understand the regulatory networks that control immune responses to pathogen challenge. Machine learning approaches are being implemented in an attempt to identify novel protein-protein interactions that can be tested experimentally. These studies are complemented by next generation sequencing data that allows us to get a glimpse of the host and pathogenic genes that are triggered during infection. We have been developing methods to analyze this rich source of genomic and transcriptomic data.

Current Projects

  • Development of a computational framework for Mycobacterium tuberculosis genetic variation and DNA methylation analysis

  • Genome assembly of next generation sequencing data for the Oryx bacillus: a species of the Mycobacterium tuberculosis complex

  • Prediction of human-Mycobacterium tuberculosis protein interaction and functional inference using the machine learning approach

  • Effects of nucleotide variation on the structure and function of human arylamine N-acetyltransferase 1 (NAT1)

  • Identification of novel inhibitors for two M.tuberculosis drug targets identified within first line drug resistant pathways

  • Susceptibility to M.tuberculosis: importance of multiple key genes in human and non-human primates

  • Unraveling Trypanosoma brucei-human protein-protein interactions: an investigation of intracellular trafficking towards the flagellar pocket and computational prediction of a flagellar interactome.

  • Identification and characterisation of miRNAs and their putative target genes in Anopheles funestus

  • Deciphering co-regulated genes in G.morsitans: A combination of in-silico and experimental approaches

  • Computational identification and characterization of iron regulatory-related proteins in Glossina morsitans

  • Development of a computational framework for gene elucidation and transcriptome profiling in Venturia inaequalis

  • Genome annotation of Venturia inaequalis

  • Discovery of transcriptional regulatory mechanisms controlling plant carotenoid biosynthesis

 

Dr Gordon Harkins 

I employ cutting-edge methods of laboratory experimentation, next-generation sequence analysis, Bayesian statistical methodologies and high-performance computing methods investigate the evolutionary underpinnings of the emergence and spread of the numerous novel plant and animal viral diseases threatening the health and food security of Africa and the rest of the developing world.

Current Projects

  •  Evolution of HIV-1 subtype C gp160 sequences in the female genital tract and plasma during acute and chronic infection

  •  A characterization of the genetic diversity in pre-genocide HIV populations in Rwanda using evidence from archival biopsy samples

  •  An investigation of the impact of HIV sharing in HIV concordant heterosexual South African couples on viral load and clinical disease progression

  •  Reconstructing the evolutionary history of HIV-1 in Cameroon

  •  The identification of biologically important secondary structures in disease-causing RNA viruses

  •  Reconstructing the evolutionary history of Psittacine beak and feather disease

  •  Characterizing the diversity of Avihepadnaviruses in parrots

  •  Spatio-temporal dynamics and evolution of pathogenicity in African maize, tomato and cassava infecting geminivirus species

  •  The effects of the widespread deployment of cassava, tomato and maize Geminivirus resistant cultivars on long-term pathogen evolution

  • Molecular diversity, evolutionary history and geographical dissemination of bipartite Begomoviruses


Dr Nicki Tiffin

I work on human genetics underlying disease, specifically in African populations, aiming to characterise genetic diversity in South Africa patient populations within the disease context. My research encompasses generic approaches to disease gene prediction, genomics underlying specific diseases in Africa including systemic lupus erythematosus and salt‑sensitive hypertension, and genetics of host response to infection by Leishmania. I am also interested in exploring the similarities and overlap of genetic and expression profiles of patients with infectious diseases, autoimmune diseases and idiopathic degenerative diseases. I am a member of two projects within the Human Heredity and Health in Africa (H3Africa) initiative funded by the Wellcome Trust, UK and the NIH, USA:  I lead the SANBI component of the H3Africa bioinformatics network; and I head the bioinformatics component of the Kidney Disease Research Network. I have a keen interest in the area of translational research that aims to bring together computational approaches, molecular biology and clinical approaches to enhance our understanding of and ability to modify the disease state.

Current projects

  • Genetics underlying salt-sensitive hypertension in South African patients

  • Genetics underlying systemic lupus erythematosus in South African patients

  • Genome wide approaches to disease gene identification in familial adult myoclonic epilepsy in a South African family

  • The relationship between genome structure and disease genes

  • Human Heredity and Health in Africa Bioinformatics Network (H3ABioNet): building bioinformatics capacity in Africa

  • Human Heredity and Health in Africa Kidney Disease Research Network: investigating genetic and environmental contributors to Kidney Disease in

  • Africa

  • SysCo Consortium: Systems biology investigation of host response to infection with Leishmania major.

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