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Dive into the research topics where Ayton Meintjes is active.

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Featured researches published by Ayton Meintjes.


Human Genetics | 2010

Genome-wide analysis of the structure of the South African Coloured Population in the Western Cape.

Erika de Wit; Wayne Delport; Chimusa E. Rugamika; Ayton Meintjes; Marlo Möller; Paul D. van Helden; Cathal Seoighe; Eileen G. Hoal

Admixed populations present unique opportunities to discover the genetic factors underlying many multifactorial diseases. The geographical position and complex history of South Africa has led to the establishment of the unique admixed population known as the South African Coloured. Not much is known about the genetic make-up of this population, and the historical record is patchy. We genotyped 959 individuals from the Western Cape area, self-identified as belonging to this population, using the Affymetrix 500k genotyping platform. This resulted in nearly 75,000 autosomal SNPs that could be compared with populations represented in the International HapMap Project and the Human Genome Diversity Project. Analysis by means of both the admixture and linkage models in STRUCTURE revealed that the major ancestral components of this population are predominantly Khoesan (32–43%), Bantu-speaking Africans (20–36%), European (21–28%) and a smaller Asian contribution (9–11%), depending on the model used. This is consistent with historical data. While of great historical and genealogical interest, this information is also essential for future admixture mapping of disease genes in this population.


BMC Genomics | 2014

Population-specific common SNPs reflect demographic histories and highlight regions of genomic plasticity with functional relevance

Ananyo Choudhury; Scott Hazelhurst; Ayton Meintjes; Ovokeraye Achinike-Oduaran; Shaun Aron; Junaid Gamieldien; Mahjoubeh Jalali Sefid Dashti; Nicola Mulder; Nicki Tiffin; Michele Ramsay

BackgroundPopulation differentiation is the result of demographic and evolutionary forces. Whole genome datasets from the 1000 Genomes Project (October 2012) provide an unbiased view of genetic variation across populations from Europe, Asia, Africa and the Americas. Common population-specific SNPs (MAF > 0.05) reflect a deep history and may have important consequences for health and wellbeing. Their interpretation is contextualised by currently available genome data.ResultsThe identification of common population-specific (CPS) variants (SNPs and SSV) is influenced by admixture and the sample size under investigation. Nine of the populations in the 1000 Genomes Project (2 African, 2 Asian (including a merged Chinese group) and 5 European) revealed that the African populations (LWK and YRI), followed by the Japanese (JPT) have the highest number of CPS SNPs, in concordance with their histories and given the populations studied. Using two methods, sliding 50-SNP and 5-kb windows, the CPS SNPs showed distinct clustering across large genome segments and little overlap of clusters between populations. iHS enrichment score and the population branch statistic (PBS) analyses suggest that selective sweeps are unlikely to account for the clustering and population specificity. Of interest is the association of clusters close to recombination hotspots. Functional analysis of genes associated with the CPS SNPs revealed over-representation of genes in pathways associated with neuronal development, including axonal guidance signalling and CREB signalling in neurones.ConclusionsCommon population-specific SNPs are non-randomly distributed throughout the genome and are significantly associated with recombination hotspots. Since the variant alleles of most CPS SNPs are the derived allele, they likely arose in the specific population after a split from a common ancestor. Their proximity to genes involved in specific pathways, including neuronal development, suggests evolutionary plasticity of selected genomic regions. Contrary to expectation, selective sweeps did not play a large role in the persistence of population-specific variation. This suggests a stochastic process towards population-specific variation which reflects demographic histories and may have some interesting implications for health and susceptibility to disease.


BMC Bioinformatics | 2014

A web-based protein interaction network visualizer

Gustavo A. Salazar; Ayton Meintjes; Gaston K. Mazandu; Richard O Akinola; Nicola Mulder

BackgroundInteraction between proteins is one of the most important mechanisms in the execution of cellular functions. The study of these interactions has provided insight into the functioning of an organism’s processes. As of October 2013, Homo sapiens had over 170000 Protein-Protein interactions (PPI) registered in the Interologous Interaction Database, which is only one of the many public resources where protein interactions can be accessed. These numbers exemplify the volume of data that research on the topic has generated. Visualization of large data sets is a well known strategy to make sense of information, and protein interaction data is no exception. There are several tools that allow the exploration of this data, providing different methods to visualize protein network interactions. However, there is still no native web tool that allows this data to be explored interactively online.ResultsGiven the advances that web technologies have made recently it is time to bring these interactive views to the web to provide an easily accessible forum to visualize PPI. We have created a Web-based Protein Interaction Network Visualizer: PINV, an open source, native web application that facilitates the visualization of protein interactions (http://biosual.cbio.uct.ac.za/pinv.html). We developed PINV as a set of components that follow the protocol defined in BioJS and use the D3 library to create the graphic layouts. We demonstrate the use of PINV with multi-organism interaction networks for a predicted target from Mycobacterium tuberculosis, its interacting partners and its orthologs.ConclusionsThe resultant tool provides an attractive view of complex, fully interactive networks with components that allow the querying, filtering and manipulation of the visible subset. Moreover, as a web resource, PINV simplifies sharing and publishing, activities which are vital in today’s research collaborative environments. The source code is freely available for download at https://github.com/4ndr01d3/biosual.


PLOS ONE | 2010

Computational analysis of candidate disease genes and variants for salt-sensitive hypertension in indigenous Southern Africans.

Nicki Tiffin; Ayton Meintjes; Rajkumar Ramesar; Vladimir B. Bajic; Brian Rayner

Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension.


Nature Communications | 2017

Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans

Ananyo Choudhury; Michele Ramsay; Scott Hazelhurst; Shaun Aron; Soraya Bardien; Gerrit Botha; Emile R. Chimusa; Alan Christoffels; Junaid Gamieldien; Mahjoubeh J. Sefid-Dashti; Fourie Joubert; Ayton Meintjes; Nicola Mulder; Raj Ramesar; Jasper Rees; Kathrine Scholtz; Dhriti Sengupta; Himla Soodyall; Philip Venter; Louise Warnich; Michael S. Pepper

The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease.African populations show a high level of genetic diversity and extensive regional admixture. Here, the authors sequence the whole genomes of 24 South African individuals of different ethnolinguistic origin and find substantive genomic divergence between two southeastern Bantu-speaking groups.


Global heart | 2017

Development of Bioinformatics Infrastructure for Genomics Research in H3Africa

Nicola Mulder; Ezekiel Adebiyi; Marion O. Adebiyi; Seun Adeyemi; Azza Elgaili Ahmed; Rehab Ahmed; Bola Akanle; Mohamed Alibi; Don Armstrong; Shaun Aron; Efejiro Ashano; Shakuntala Baichoo; Alia Benkahla; David K. Brown; Emile R. Chimusa; Faisal M. Fadlelmola; Dare Falola; Segun Fatumo; Kais Ghedira; Amel Ghouila; Scott Hazelhurst; Itunuoluwa Isewon; Segun Jung; Samar K. Kassim; Jonathan K. Kayondo; Mamana Mbiyavanga; Ayton Meintjes; Somia Mohammed; Abayomi Mosaku; Ahmed Moussa

BACKGROUND 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 (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNets role has evolved in response to changing needs from the consortium and the African bioinformatics community. OBJECTIVES H3ABioNet 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 enrollment, 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. Because 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. CONCLUSIONS 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 programs. Here, we describe the infrastructure and how it has affected genomics and bioinformatics research in Africa.


F1000Research | 2014

PPI layouts : BioJS components for the display of Protein-Protein Interactions

Gustavo A. Salazar; Ayton Meintjes; Nicola Mulder

Summary: We present two web-based components for the display of Protein-Protein Interaction networks using different self-organizing layout methods: force-directed and circular. These components conform to the BioJS standard and can be rendered in an HTML5-compliant browser without the need for third-party plugins. We provide examples of interaction networks and how the components can be used to visualize them, and refer to a more complex tool that uses these components. Availability: http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7753


PLOS Computational Biology | 2017

Assessing computational genomics skills: Our experience in the H3ABioNet African bioinformatics network

C. Victor Jongeneel; Ovokeraye Achinike-Oduaran; Ezekiel Adebiyi; Marion O. Adebiyi; Seun Adeyemi; Bola Akanle; Shaun Aron; Efejiro Ashano; Hocine Bendou; Gerrit Botha; Emile R. Chimusa; Ananyo Choudhury; Ravikiran Donthu; Jenny Drnevich; Oluwadamila Falola; Christopher J. Fields; Scott Hazelhurst; Liesl M. Hendry; Itunuoluwa Isewon; Radhika S. Khetani; Judit Kumuthini; Magambo Phillip Kimuda; Lerato Magosi; Liudmila Sergeevna Mainzer; Suresh Maslamoney; Mamana Mbiyavanga; Ayton Meintjes; Danny Mugutso; Phelelani T. Mpangase; Richard J. Munthali

The H3ABioNet pan-African bioinformatics network, which is funded to support the Human Heredity and Health in Africa (H3Africa) program, has developed node-assessment exercises to gauge the ability of its participating research and service groups to analyze typical genome-wide datasets being generated by H3Africa research groups. We describe a framework for the assessment of computational genomics analysis skills, which includes standard operating procedures, training and test datasets, and a process for administering the exercise. We present the experiences of 3 research groups that have taken the exercise and the impact on their ability to manage complex projects. Finally, we discuss the reasons why many H3ABioNet nodes have declined so far to participate and potential strategies to encourage them to do so.


PLOS ONE | 2013

Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells.

Alice Riedel; Boitumelo Mofolo; Elita Avota; Sibylle Schneider-Schaulies; Ayton Meintjes; Nicola Mulder; Susanne Kneitz

Background Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. Methods To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. Results Applying our algorithm to the data, 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. Conclusions PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression.


PLOS ONE | 2018

A common molecular signature of patients with sickle cell disease revealed by microarray meta-analysis and a genome-wide association study

Cherif Ben Hamda; Raphael Z Sangeda; Liberata Mwita; Ayton Meintjes; Siana Nkya; Sumir Panji; Nicola Mulder; Lamia Guizani-Tabbane; Alia Benkahla; Julie Makani; Kais Ghedira

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 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.

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Scott Hazelhurst

University of the Witwatersrand

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Shaun Aron

University of the Witwatersrand

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Ananyo Choudhury

University of the Witwatersrand

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Gerrit Botha

University of Cape Town

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