Browsing by Author "Van Heusden, Peter"

Now showing 1 - 13 of 13
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    The African Coelecanth genome provides insights into tetrapod evolution
    (Macmillan Publishers, 2013) Christoffels, Alan; Hesse, Uljana; Gamieldien, Junaid; Panji, Sumir; Picone, Barbara; Van Heusden, Peter
    The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
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    Capacity building for whole genome sequencing of Mycobacterium tuberculosis and bioinformatics in high TB burden countries
    (Oxford University Press, 2020) Van Heusden, Peter
    Background Whole-genome sequencing (WGS) is increasingly used for Mycobacterium tuberculosis (Mtb) research. Countries with the highest tuberculosis (TB) burden face important challenges to integrate WGS into surveillance and research. Methods We assessed the global status of Mtb WGS and developed a 3-week training course coupled with long-term mentoring and WGS infrastructure building. Training focused on genome sequencing, bioinformatics and development of a locally relevant WGS research project. The aim of the long-term mentoring was to support trainees in project implementation and funding acquisition. The focus of WGS infrastructure building was on the DNA extraction process and bioinformatics. Findings Compared to their TB burden, Asia and Africa are grossly underrepresented in Mtb WGS research. Challenges faced resulted in adaptations to the training, mentoring and infrastructure building. Out-of-date laptop hardware and operating systems were overcome by using online tools and a Galaxy WGS analysis pipeline. A case studies approach created a safe atmosphere for students to formulate and defend opinions. Because quality DNA extraction is paramount for WGS, a biosafety level 3 and general laboratory skill training session were added, use of commercial DNA extraction kits was introduced and a 2-week training in a highly equipped laboratory was combined with a 1-week training in the local setting. Interpretation By developing and sharing the components of and experiences with a sequencing and bioinformatics training program, we hope to stimulate capacity building programs for Mtb WGS and empower high-burden countries to play an important role in WGS-based TB surveillance and research.
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    Chromosomal-level assembly of the Asian seabass genome using long sequence reads and multi-layered scaffolding
    (Public Library of Science, 2016) Vij, Shubha; Van Heusden, Peter; Christoffels, Alan; Mbandi, Stanley K.; Mwangi, Sarah
    We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species’ native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics.
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    Combat-tb: an integrated environment for m tuberculosis data analysis
    (Universty of the Western Cape, 2018) Van Heusden, Peter
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    Getting the most out of HTC with workflows
    (University of the Western Cape, 2018) Van Heusden, Peter
    Slides for a presentation on High Throughput Computing and workflows including . Commentary on the contract between High Throughput Computing (HTC) and High Performance Computing (HPC). A description of the layers of the Research Computing stack . Theory of workflow design and considerations in workflow design
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    Getting the Most out of HTC with Workflows
    (Universty of the Western Cape, 2018) Van Heusden, Peter; Koch, Christina
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    High throughput computing in bioinformatics: workflows, containers and emerging paradigms
    (University of the Western Cape, 2018) Van Heusden, Peter
    Next Generation Sequencing has brought genomic analysis within the range of a great number of laboratories, while increasing the demand for bioinformatic analysis. These typically comprise workflows composed out of chains of analyses with data flowing between workflow steps. Such analysis is amenable to High Throughput Computing, a form of high performance computing characterised by a focus on overall analysis throughput rather than optimisation of a single application. In recent years workflow languages and container technologies have become a key part in composing efficient, reproducible and re-usable bionformatic workflows. These technologies, however, pose a challenge for High Performance Computing providers as they require different characteristics from an execution environment to that provided by traditional HPC clusters. These challenges will be discussed and some approaches to solving them will be discussed.
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    Inferring bona fide transfrags in RNA-Seq derived-transcriptome assemblies of non-model organisms
    (BioMed Central, 2015) Mbandi, Stanley K.; Hesse, Uljana; Van Heusden, Peter; Christoffels, Alan
    Background: De novo transcriptome assembly of short transcribed fragments (transfrags) produced from sequencing-by-synthesis technologies often results in redundant datasets with differing levels of unassembled, partially assembled or mis-assembled transcripts. Post-assembly processing intended to reduce redundancy typically involves reassembly or clustering of assembled sequences. However, these approaches are mostly based on common word heuristics and often create clusters of biologically unrelated sequences, resulting in loss of unique transfrags annotations and propagation of mis-assemblies. Results: Here, we propose a structured framework that consists of a few steps in pipeline architecture for Inferring Functionally Relevant Assembly-derived Transcripts (IFRAT). IFRAT combines 1) removal of identical subsequences, 2) error tolerant CDS prediction, 3) identification of coding potential, and 4) complements BLAST with a multiple domain architecture annotation that reduces non-specific domain annotation. We demonstrate that independent of the assembler, IFRAT selects bona fide transfrags (with CDS and coding potential) from the transcriptome assembly of a model organism without relying on post-assembly clustering or reassembly. The robustness of IFRAT is inferred on RNA-Seq data of Neurospora crassa assembled using de Bruijn graph-based assemblers, in single (Trinity and Oases-25) and multiple (Oases-Merge and additive or pooled) k-mer modes. Single k-mer assemblies contained fewer transfrags compared to the multiple k-mer assemblies. However, Trinity identified a comparable number of predicted coding sequence and gene loci to Oases pooled assembly. IFRAT selects bona fide transfrags representing over 94% of cumulative BLAST-derived functional annotations of the unfiltered assemblies. Between 4-6% are lost when orphan transfrags are excluded and this represents only a tiny fraction of annotation derived from functional transference by sequence similarity. The median length of bona fide transfrags ranged from 1.5kb (Trinity) to 2kb (Oases), which is consistent with the average coding sequence length in fungi. The fraction of transfrags that could be associated with gene ontology terms ranged from 33-50%, which is also high for domain based annotation. We showed that unselected transfrags were mostly truncated and represent sequences from intronic, untranslated (5′ and 3′) regions and non-coding gene loci. Conclusions: IFRAT simplifies post-assembly processing providing a reference transcriptome enriched with functionally relevant assembly-derived transcripts for non-model organism.
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    An integrated and comparative approach towards identification, characterization and functional annotation of candidate genes for drought tolerance in sorghum (Sorghum bicolor (L.) Moench)
    (BioMed Central, 2017) Woldesemayat, Adugna Abdi; Van Heusden, Peter; Ndimba, Bongani K.; Christoffels, Alan
    BACKGROUND: Drought is the most disastrous abiotic stress that severely affects agricultural productivity worldwide. Understanding the biological basis of drought-regulated traits, requires identification and an in-depth characterization of genetic determinants using model organisms and high-throughput technologies. However, studies on drought tolerance have generally been limited to traditional candidate gene approach that targets only a single gene in a pathway that is related to a trait. In this study, we used sorghum, one of the model crops that is well adapted to arid regions, to mine genes and define determinants for drought tolerance using drought expression libraries and RNA-seq data. RESULTS: We provide an integrated and comparative in silico candidate gene identification, characterization and annotation approach, with an emphasis on genes playing a prominent role in conferring drought tolerance in sorghum. A total of 470 non-redundant functionally annotated drought responsive genes (DRGs) were identified using experimental data from drought responses by employing pairwise sequence similarity searches, pathway and interprodomain analysis, expression profiling and orthology relation. Comparison of the genomic locations between these genes and sorghum quantitative trait loci (QTLs) showed that 40% of these genes were co-localized with QTLs known for drought tolerance. The genome reannotation conducted using the Program to Assemble Spliced Alignment (PASA), resulted in 9.6% of existing single gene models being updated. In addition, 210 putative novel genes were identified using AUGUSTUS and PASA based analysis on expression dataset. Among these, 50% were single exonic, 69.5% represented drought responsive and 5.7% were complete gene structure models. Analysis of biochemical metabolism revealed 14 metabolic pathways that are related to drought tolerance and also had a strong biological network, among categories of genes involved. Identification of these pathways, signifies the interplay of biochemical reactions that make up the metabolic network, constituting fundamental interface for sorghum defence mechanism against drought stress. CONCLUSIONS: This study suggests untapped natural variability in sorghum that could be used for developing drought tolerance. The data presented here, may be regarded as an initial reference point in functional and comparative genomics in the Gramineae family.
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    Messages from SA covid vax chat Telegram channel
    (University of the Western Cape, 2024) Van Heusden, Peter
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    Taste and odorant receptors of the coelecanth- a gene repertoire in transition
    (Wiley, 2014) Picone, Barbara; Hesse, Uljana; Panji, Sumir; Van Heusden, Peter; Jonas, Mario; Christoffels, Alan
    G-protein coupled chemosensory receptors (GPCR-CRs) aid in the perception of odors and tastes in vertebrates. So far, six GPCR-CR families have been identified that are conserved in most vertebrate species. Phylogenetic analyses indicate differing evolutionary dynamics between teleost fish and tetrapods. The coelacanth Latimeria chalumnae belongs to the lobe-finned fishes, which represent a phylogenetic link between these two groups. We searched the genome of L. chalumnae for GPCR-CRs and found that coelacanth taste receptors are more similar to those in tetrapods than in teleost fish: two coelacanth T1R2s co-segregate with the tetrapod T1R2s that recognize sweet substances, and our phylogenetic analyses indicate that the teleost T1R2s are closer related to T1R1s (umami taste receptors) than to tetrapod T1R2s. Furthermore, coelacanths are the first fish with a large repertoire of bitter taste receptors (58 T2Rs). Considering current knowledge on feeding habits of coelacanths the question arises if perception of bitter taste is the only function of these receptors. Similar to teleost fish, coelacanths have a variety of olfactory receptors (ORs) necessary for perception of water-soluble substances. However, they also have seven genes in the two tetrapod OR subfamilies predicted to recognize airborne molecules. The two coelacanth vomeronasal receptor families are larger than those in teleost fish, and similar to tetrapods, form V1R and V2R monophyletic clades. This may point to an advanced development of the vomeronasal organ as reported for lungfish. Our results show that the intermediate position of Latimeria in the phylogeny is reflected in its GPCR-CR repertoire.
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    The COMBAT-TB Project
    (University of the Western Cape, 2018) Van Heusden, Peter
    Presentation to Galaxy Africa 2018 (http://galaxyafrica.sanbi.ac.za/) conference on COMBAT TB project.
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    Virome assembly and annotation: A surprise in the Namib Desert
    (Frontiers Research Foundation, 2017) Hesse, Uljana; Van Heusden, Peter; Kirby, Bronwyn; Olonade, Israel; van Zyl, Leonardo Joaquim; Trindade, Marla
    Sequencing, assembly, and annotation of environmental virome samples is challenging. Methodological biases and differences in species abundance result in fragmentary read coverage; sequence reconstruction is further complicated by the mosaic nature of viral genomes. In this paper, we focus on biocomputational aspects of virome analysis, emphasizing latent pitfalls in sequence annotation. Using simulated viromes that mimic environmental data challenges we assessed the performance of five assemblers (CLC-Workbench, IDBA-UD, SPAdes, RayMeta, ABySS). Individual analyses of relevant scaffold length fractions revealed shortcomings of some programs in reconstruction of viral genomes with excessive read coverage (IDBA-UD, RayMeta), and in accurate assembly of scaffolds ?50 kb (SPAdes, RayMeta, ABySS). The CLC-Workbench assembler performed best in terms of genome recovery (including highly covered genomes) and correct reconstruction of large scaffolds; and was used to assemble a virome from a copper rich site in the Namib Desert. We found that scaffold network analysis and cluster-specific read reassembly improved reconstruction of sequences with excessive read coverage, and that strict data filtering for non-viral sequences prior to downstream analyses was essential. In this study we describe novel viral genomes identified in the Namib Desert copper site virome. Taxonomic affiliations of diverse proteins in the dataset and phylogenetic analyses of circovirus-like proteins indicated links to the marine habitat. Considering additional evidence from this dataset we hypothesize that viruses may have been carried from the Atlantic Ocean into the Namib Desert by fog and wind, highlighting the impact of the extended environment on an investigated niche in metagenome studies.