The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity ...among African individuals has been surveyed
. Here we performed whole-genome sequencing analyses of 426 individuals-comprising 50 ethnolinguistic groups, including previously unsampled populations-to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon-but in other genes, variants denoted as 'likely pathogenic' in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.
Genomics policy development involves assessing a wide range of issues extending from specimen collection and data sharing to whether and how to utilize advanced technologies in clinical practice and ...public health initiatives. A survey was conducted among African scientists and stakeholders with an interest in genomic medicine, seeking to evaluate: 1) Their knowledge and understanding of the field. 2) The institutional environment and infrastructure available to them. 3) The state and awareness of the field in their country. 4) Their perception of potential barriers to implementation of precision medicine. We discuss how the information gathered in the survey could instruct the policies of African institutions seeking to implement precision, and more specifically, genomic medicine approaches in their health care systems in the following areas: 1) Prioritization of infrastructures. 2) Need for translational research. 3) Information dissemination to potential users. 4) Training programs for specialized personnel. 5) Engaging political stakeholders and the public. A checklist with key requirements to assess readiness for implementation of genomic medicine programs is provided to guide the process from scientific discovery to clinical application.
Genomics data are currently being produced at unprecedented rates, resulting in increased knowledge discovery and submission to public data repositories. Despite these advances, genomic information ...on African-ancestry populations remains significantly low compared with European- and Asian-ancestry populations. This information is typically segmented across several different biomedical data repositories, which often lack sufficient fine-grained structure and annotation to account for the diversity of African populations, leading to many challenges related to the retrieval, representation and findability of such information. To overcome these challenges, we developed the African Genomic Medicine Portal (AGMP), a database that contains metadata on genomic medicine studies conducted on African-ancestry populations. The metadata is curated from two public databases related to genomic medicine, PharmGKB and DisGeNET. The metadata retrieved from these source databases were limited to genomic variants that were associated with disease aetiology or treatment in the context of African-ancestry populations. Over 2000 variants relevant to populations of African ancestry were retrieved. Subsequently, domain experts curated and annotated additional information associated with the studies that reported the variants, including geographical origin, ethnolinguistic group, level of association significance and other relevant study information, such as study design and sample size, where available. The AGMP functions as a dedicated resource through which to access African-specific information on genomics as applied to health research, through querying variants, genes, diseases and drugs. The portal and its corresponding technical documentation, implementation code and content are publicly available.
The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data ...analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.
Abstract
Childhood cancers present unique challenges for variant interpretation in a clinical context due to their rarity, low mutation burden, diversity of molecular alterations, and heterogeneity ...among patients. Consequently, genes and variants associated with childhood tumors are under-represented in public cancer databases and knowledgebases. A focused effort is needed for the structured curation of genetic variant-level data to document diagnostic, prognostic, and therapeutic biomarkers for childhood cancers. The Pediatric Cancer Curation Advancement Subcommittee (PCCAS), a collaboration between the Clinical Interpretations of Variants in Cancer knowledgebase (CIViC; civicdb.org), the ClinGen Somatic Pediatric Cancer Taskforce, Disease Ontology (DO; disease-ontology.org) and CIViCmine (bionlp.bcgsc.ca/civicmine/), is addressing this challenge through enhanced curation, tagging, and automation.
PCCAS created a pediatric specific curation standard operating procedure (SOP) to harmonize pediatric evidence entered in CIViC. Our SOP provides general guidance and considerations to define and classify childhood cancers and to represent childhood cancer evidence on a spectrum of age-related incidence and presentation. For instance, pediatric evidence in CIViC is now tagged using Human Phenotype Ontology (HPO) age of onset terms, allowing pediatric evidence to be easily searched, tracked, and sorted. We also initiated the addition of new age of onset terms to enhance the granularity of these tags.
WHO ICD-O nomenclature has been chosen for pediatric disease classification in CIViC. ICD-O provides updated terminology including specific genetic subtypes, which are important in pediatric cancers where their underlying molecular profiles often define the disease. To aid curator selection of disease, we verified pediatric relevant ICD-O terms inclusion in DO and restructured DO disease hierarchies to ensure proper mapping.
CIViC highlights our pediatric cancer initiative in multiple areas including a homepage feature linking directly to a dedicated pediatric advanced search that returns all evidence tagged with pediatric or young adult age of onset. Most importantly, our childhood specific SOP and initiatives are included in all ClinGen Somatic Cancer and CIViC training sessions for consistent implementation.
CIViCmine supports CIViC by using natural language processing to identify important cancer biomarkers in the literature. To better identify pediatric biomarkers, we are adapting and refining CIViCmine to use MeSH terms and other approaches to enhance accuracy in the identification of childhood evidence in both the literature and CIViC. In conclusion, implementation of these procedures, features, and automation are pushing to make childhood cancer variant evidence more accessible and interpretable.
Citation Format: Jason Saliba, Jake Lever, Kilannin Krysiak, Arpad Danos, Alex Wagner, Heather E. Williams, Laveniya Satgunaseelan, David Meredith, Cameron J. Grisdale, Chimene Kesserwan, Jianling Ji, Shruti Rao, Catherine Cottrell, Alanna Church, Mark Evans, Yasmina Jaufeerally-Fakim, Lynn M. Schriml, Angshumoy Roy, Gordana Raca, Malachi Griffith, Obi L. Griffith. Enhancing pediatric cancer variant curation and representation through standardized classification and automation abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1193.
SUMMARY
Suppression subtractive hybridization was used to isolate the genes which are specifically up‐regulated in the biotrophic phase of the incompatible interaction between a potato genotype, 1512 ...c(16), containing the resistance gene R2, and a Phytophthora infestans isolate containing the avirulence gene Avr2. Eight cDNAs were up‐regulated in the biotrophic phase of the incompatible interaction. Seven of these were also up‐regulated in the compatible interaction, but not until late in the necrotrophic phase. Amongst the sequences to be isolated were genes encoding the cysteine protease cathepsin B, StCathB, and an oxysterol binding protein, StOBP1; equivalent genes are involved in programmed cell death (PCD) processes in animals, but have yet to be implicated in such processes in plants. Whereas StOBP1 was up‐regulated early in potato plants containing either R gene‐mediated or moderate to high levels of field resistance, the highest levels of up‐regulation of StCathB were observed early in R gene‐mediated resistance but gradually increased from the early to late stages of field resistance, revealing these genes to be components of independent defence pathways and providing a means of distinguishing between these forms of resistance. StOBP1 was up‐regulated by oligogalacturonides (plant cell wall breakdown products generated by pectinase activities), indicating that it is also a component of a general, non‐specific defence pathway and is unlikely to play a role in PCD. In contrast, the expression of StCathB was unaffected by oligogalacturonide treatment, further associating its up‐regulation specifically with the gene‐for‐gene interaction.
...the workshop contributed towards the facilitation of metagenomics research by engaging researchers from laboratories across the continent providing expertise and relevant content, and hopefully ...provided additional capacity building in the form of collaborative efforts between the participants, thus fulfilling the two primary goals of the H3Africa initiative. ...we have made an effort to compile most of the material into an online resource accessible via the Web, with most contributions made publicly available (to the extent possible), including-importantly-the Ubuntu/QIIME VirtualBox image with data and software already pre-packaged for further use by the wider community.
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