Background and objectives
Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a Pan African bioinformatics network, was established to build capacity specifically to enable H3Africa researchers to analyse their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet’s role has evolved in response to changing needs from the consortium and the African bioinformatics community. The network set out to develop core bioinformatics infrastructure and capacity for genomics research in various aspects of data collection, transfer, storage and analysis.
Methods and results
Various resources have been developed to address genomic data management and analysis needs of H3Africa researchers and other scientific communities on the continent. NetMap was developed and used to build an accurate picture of network performance within Africa and between Africa and the rest of the world, and Globus Online has been rolled out to facilitate data transfer. A participant recruitment database was developed to monitor participant enrolment, and data is being harmonized through the use of ontologies and controlled vocabularies. The standardized metadata will be integrated to provide a search facility for H3Africa data and biospecimens. Since H3Africa projects are generating large-scale genomic data, facilities for analysis and interpretation are critical. H3ABioNet is implementing several data analysis platforms that provide a large range of bioinformatics tools or workflows, such as Galaxy, the Job Management System and eBiokits. A set of reproducible, portable and cloud scalable pipelines to support the multiple H3Africa data types are also being developed and dockerized to enable execution on multiple computing infrastructures. In addition, new tools have been developed for analysis of the uniquely divergent African data and for downstream interpretation of prioritized variants. To provide support for these and other bioinformatics queries, an online bioinformatics helpdesk backed by broad consortium expertise has been established. Further support is provided by means of various modes of bioinformatics training.
Conclusion
For the past 4 years, the development of infrastructure support and human capacity through H3ABioNet, have significantly contributed to the establishment of African scientific networks, data analysis facilities and training programmes. Here, we describe the infrastructure and how it has impacted genomics and bioinformatics research in Africa.
Saturated fatty acids (SFA) have been reported to alter organelle integrity and function in many cell types, including muscle and pancreatic β-cells, adipocytes, hepatocytes and cardiomyocytes. SFA accumulation results in increased amounts of ceramides/sphingolipids and saturated phospholipids (PL). In this study, using a yeast-based model that recapitulates most of the trademarks of SFA-induced lipotoxicity in mammalian cells, we demonstrate that these lipid species act at different levels of the secretory pathway. Ceramides mostly appear to modulate the induction of the unfolded protein response and the transcription of nutrient transporters destined to the cell surface. On the other hand, saturated PL, by altering membrane properties, directly impact vesicular budding at later steps in the secretory pathway, i.e. at the trans-Golgi Network level. They appear to do so by increasing lipid order within intracellular membranes which, in turn, alters the recruitment of loose lipid packing-sensing proteins, required for optimal budding, to nascent vesicles. We propose that this latter general mechanism could account for the well-documented deleterious impacts of fatty acids on the last steps of the secretory pathway in several cell types.
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