Fine-scale variability in coral bleaching and mortality during a marine heatwave

Coral bleaching and mortality can show significant spatial and taxonomic heterogeneity at local scales, highlighting the need to understand the fine-scale drivers and impacts of thermal stress. In this study, we used structure-from-motion photogrammetry to track coral bleaching, mortality, and changes in community composition during the 2019 marine heatwave in Kāneʻohe Bay, Hawaiʻi. We surveyed 30 shallow reef patches every 3 weeks for the duration of the bleaching event (August-December) and one year after, resulting in a total of 210 large-area, high-resolution photomosaics that enabled us to follow the fate of thousands of coral colonies through time. We also measured environmental variables such as temperature, sedimentation, depth, and wave velocity at each of these sites, and extracted estimates of habitat complexity (rugosity R and fractal dimension D) from digital elevation models to better understand their effects on patterns of bleaching and mortality. We found that up to 80% of corals experienced moderate to severe bleaching in this period, with peak bleaching occurring in October when heat stress (Degree Heating Weeks) reached its maximum. Mortality continued to accumulate as bleaching levels dropped, driving large declines in more heat-susceptible species (77% loss of Pocillopora cover) and moderate declines in heat-tolerant species (19% and 23% for Porites compressa and Montipora capitata, respectively). Declines in live coral were accompanied by a rapid increase in algal cover across the survey sites. Spatial differences in bleaching were significantly linked to habitat complexity and coral species composition, with reefs that were dominated by Pocillopora experiencing the most severe bleaching. Mortality was also influenced by species composition, fractal dimension, and site-level differences in thermal stress. Our results show that spatial heterogeneity in the impacts of bleaching are driven by a mix of environmental variation, habitat complexity, and differences in assemblage composition

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Challenges and opportunities for integrating structural variants into conservation genomics.

Reduced costs and increased accessibility of whole-genome sequencing (WGS) technologies continue to facilitate the use of genomic data to inform conservation management. Whole- genome single nucleotide polymorphisms (SNPs) are increasingly used to estimate population diversity and differentiation to inform translocations, identify signatures of local adaptation or hybridisation and introgression, and inform conservation breeding programs. In general, these conservation management interventions aim to ensure populations have sufficient genetic diversity to adapt to environmental change. However, SNPs are but one type of variant and may not holistically capture genetic diversity or evolutionary potential. Structural variants (SVs), which are large variants typically defined as ≥50bp in length, include deletions, duplications, insertions, inversions and translocations. SVs have been found to be a significant source of genetic diversity as they intersect with genes and gene regions more frequently and impact more genomic content overall than SNPs. Further, mounting evidence indicates that SVs play an important role in the evolution of adaptive traits. However, SVs remain largely understudied in a conservation context. To date, the majority of SV research has taken place in well-resourced fields (e.g., primary industry and human health) and the minimum sequencing and bioinformatic thresholds to leverage conservation genomics data for SV studies is unclear. This thesis aims to explore the challenges and opportunities associated with studying SVs in non-model species of conservation concern, and to identify potential strategies for incorporating SVs into the conservation genomics toolbox. Chapter 2, published as a Perspective in the Molecular Ecology ‘Whole Genome Sequencing in Molecular Ecology’ Special Issue, is a product of all of the learnings of this thesis. In this Perspective, my co-authors and I discuss the relative performance of sequencing technologies and bioinformatic approaches in a conservation context. We examine the wider literature for emerging tools and strategies aimed at investigating SVs in small populations. Insights gained from these well resourced fields are likely to inform approaches best suited to investigating SVs in non-model organisms, especially since there is very little research outside these well studied species and fewer still that investigate SVs in a conservation context. We also argue that advances like long-read sequencing and genome graphs will be increasingly utilised in conservation genomics. In the meantime, gaps remain in our understanding of the limitations and expected systematic biases introduced by short-read data for population SV studies in non-model organisms. Extensive benchmarking studies within the human genomics space demonstrate that whole genome short-read sequence data is prone to high false-positive rates and systematic biases towards detecting smaller SVs. However, short-read resequence data is currently one of the most common WGS data types available for species of conservation concern. Further, the resources required to establish and validate a reliable ‘truth’ set for SV benchmarking and validation are likely unattainable for many threatened species. In Chapter 3 we leverage an unprecedented population-level short-read resequence data set and a high-quality, chromosomally assembled reference genome for the critically endangered kākāpō (Strigops habroptilus) to explore four strategies for SV discovery and genotyping. My coauthors and I compare variability in SV call sets and genotype consistency to explore how this may impact SV population studies. We find a high level of variability in SV type, size distribution, and number of SVs per chromosome between the four approaches. However, SVs successfully recover known population structure in the dataset. These results indicate that, although SV studies with short- read data may be informative, caution should be exercised when interpreting results. Taking the insights gained from Chapter 3, in Chapter 4 we shift our focus to the most endangered breeding bird in Aotearoa New Zealand, the New Zealand fairy tern/tara iti (Sternula nereis davisae). Tara iti are one of three subspecies that include the Australian fairy tern (Sternula nereis nereis) and New Caledonian fairy tern (Sternula nereis exsul). All taxa are either highly threatened or experiencing declines due to anthropogenic disturbance, introduced predators and a changing climate. Observation data indicates that tara iti have persisted as a small population since the 1950’s, but this is likely an underestimate. To investigate the level of genome-wide diversity within, and population differentiation between tara iti and the closely related Australian fairy tern, we utilise short-read WGS data aligned to a chromosomally scaffolded reference genome for the common tern (Sterna hirundo) to detect SNPs and SVs. Overall, there was a high level of congruence between SNP and SV data. For example, we observed much lower levels of heterozygosity in SNP data and a high proportion of fixed SVs in tara iti. This is consistent with the expectation of a persistently small population size for tara iti. In addition, both SNP and SV data demonstrated a high level population differentiation between the two taxa. These results represent the ‘first steps’ towards integrating SNPs and SVs to better inform conservation management of tara iti and have implications for the taxonomic status of the fairy tern species complex. In Chapter 2 we highlight the exciting promise of genome graphs, which capture population variation in genome structure and sequence by aligning multiple reference individuals. Genome graphs can facilitate the discovery and genotyping of large and complex variants, because they remove any bias that comes from having a single linear reference genome. In Chapter 5 we present the first steps towards a kākāpō pangenome. We target 12 individuals in the kākāpō population, including 10 highly represented ‘founding’ individuals, to generate long-read data using Oxford Nanopore Technology. Using a high-quality chromosomally assembled kākāpō reference genome (Jane’s genome) as a guide, we target chromosome 7 for graph construction as it contains four functional genes of interest (Toll-like Receptors, or TLRs). Assemblies for seven individuals alongside Jane’s genome were used to construct the graph. We observe depth outliers along the length of the graphs for chromosome 7 and each TLR, likely indicating poorly assembled and/or highly repetitive regions. When examining the graph topology for each of the four TLRs, we observe large putative SVs in two of them. However, more work is required to determine whether these represent assembly errors or reflect true variation. These results are exciting as they represent the first known attempt to implement genome graphs in a species of conservation concern. Finally, Chapter 6 provides a summary of the main findings of this thesis and revisits the exciting promise of integrating SVs into the conservation genomics toolkit. The appendices contain two additional manuscripts that I co-authored during my PhD and a collation of reports prepared for Te Arai and Mangawhai Shorebirds Trust and Department of Conservation. This combined research represents an exciting step towards the integration of SVs into conservation decision frameworks for species of conservation concern globally

Fine-scale variability in coral bleaching and mortality during a marine heatwave

Coral bleaching and mortality can show significant spatial and taxonomic heterogeneity at local scales, highlighting the need to understand the fine-scale drivers and impacts of thermal stress. In this study, we used structure-from-motion photogrammetry to track coral bleaching, mortality, and changes in community composition during the 2019 marine heatwave in Kāneʻohe Bay, Hawaiʻi. We surveyed 30 shallow reef patches every 3 weeks for the duration of the bleaching event (August-December) and one year after, resulting in a total of 210 large-area, high-resolution photomosaics that enabled us to follow the fate of thousands of coral colonies through time. We also measured environmental variables such as temperature, sedimentation, depth, and wave velocity at each of these sites, and extracted estimates of habitat complexity (rugosity R and fractal dimension D) from digital elevation models to better understand their effects on patterns of bleaching and mortality. We found that up to 80% of corals experienced moderate to severe bleaching in this period, with peak bleaching occurring in October when heat stress (Degree Heating Weeks) reached its maximum. Mortality continued to accumulate as bleaching levels dropped, driving large declines in more heat-susceptible species (77% loss of Pocillopora cover) and moderate declines in heat-tolerant species (19% and 23% for Porites compressa and Montipora capitata, respectively). Declines in live coral were accompanied by a rapid increase in algal cover across the survey sites. Spatial differences in bleaching were significantly linked to habitat complexity and coral species composition, with reefs that were dominated by Pocillopora experiencing the most severe bleaching. Mortality was also influenced by species composition, fractal dimension, and site-level differences in thermal stress. Our results show that spatial heterogeneity in the impacts of bleaching are driven by a mix of environmental variation, habitat complexity, and differences in assemblage composition

Illness progression in chronic fatigue syndrome: a shifting immune baseline.

BACKGROUND: Validation of biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) across data sets has proven disappointing. As immune signature may be affected by many factors, our objective was to explore the shift in discriminatory cytokines across ME/CFS subjects separated by duration of illness. METHODS: Cytokine expression collected at rest across multiple studies for female ME/CFS subjects (i) 18 years or younger, ill for 2 years or less (n = 18), (ii) 18–50 years of age, ill for 7 years (n = 22), and (iii) age 50 years or older (n = 28), ill for 11 years on average. Control subjects were matched for age and body mass index (BMI). Data describing the levels of 16 cytokines using a chemiluminescent assay was used to support the identification of separate linear classification models for each subgroup. In order to isolate the effects of duration of illness alone, cytokines that changed significantly with age in the healthy control subjects were excluded a priori. RESULTS: Optimal selection of cytokines in each group resulted in subsets of IL-1α, 6, 8, 15 and TNFα. Common to any 2 of 3 groups were IL-1α, 6 and 8. Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration sub-groups produced ME/CFS classification accuracies of 75–88 %. The contribution of IL-1α, higher in recently ill adolescent ME/CFS subjects was progressively less important with duration. While high levels of IL-8 screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years. Similarly, while low levels of IL-6 suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years. CONCLUSIONS: These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-016-0142-3) contains supplementary material, which is available to authorized users

GA4GH: International policies and standards for data sharing across genomic research and healthcare

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits