Inferring the Characteristics of Ancient Populations using Bioinformatic Analysis of Genome-wide DNA Sequencing Data

In this thesis, I apply, evaluate, and develop methods for learning about past populations from genome-wide sequencing data. Specifically, I: • apply methods based on random genetic drift between populations, to determine that pre-Holocene gene flow occurred between the ancestors of domestic cattle (Bos primigenius) and European bison (Bison priscus), and that the contribution of Bos genealogy to the bison lineage was less than 10 %; • use simulations to assess the impact of short genomic scaffolds when inferring past populations sizes with the pairwise sequentially Markov coalescent, and show that population size inferences can be robust for scaffold lengths as short as 100 kb; • perform genetic sex determination of ancient DNA specimens to show that bison (Bison spp.) and brown bear (Ursus arctos) specimens are approximately 75% male, and that male-biased observations likely stem from the ecological and social structures of the populations; • and develop a suite of software tools for processing hairpin bisulfite sequencing data, which can be used to investigate genome-wide DNA methylation levels in ancient DNA.Thesis (Ph.D.) -- University of Adelaide, School of Biological Sciences, 201

Distance Geometry for Kissing Spheres

A kissing sphere is a sphere that is tangent to a fixed reference ball. We develop in this paper a distance geometry for kissing spheres, which turns out to be a generalization of the classical Euclidean distance geometry.Comment: 11 pages, 2 picture

Prioritization of HCV treatment in the direct-acting antiviral era: an economic evaluation

BACKGROUND & AIMS: We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID). METHODS: A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment. RESULTS: The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage. CONCLUSIONS: Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high

A genomic exploration of the early evolution of extant cats and their sabre-toothed relatives

Background: The evolutionary relationships of Felidae during their Early-Middle Miocene radiation is contentious. Although the early common ancestors have been subsumed under the grade-group Pseudaelurus, this group is thought to be paraphyletic, including the early ancestors of both modern cats and extinct sabretooths. Methods: Here, we sequenced a draft nuclear genome of Smilodon populator, dated to 13,182 ± 90 cal BP, making this the oldest palaeogenome from South America to date, a region known to be problematic for ancient DNA preservation. We analysed this genome, together with genomes from other extinct and extant cats to investigate their phylogenetic relationships. Results: We confirm a deep divergence (~20.65 Ma) within sabre-toothed cats. Through the analysis of both simulated and empirical data, we show a lack of gene flow between Smilodon and contemporary Felidae. Conclusions: Given that some species traditionally assigned to Pseudaelurus originated in the Early Miocene ~20 Ma, this indicates that some species of Pseudaelurus may be younger than the lineages they purportedly gave rise to, further supporting the hypothesis that Pseudaelurus was paraphyletic

A genomic exploration of the early evolution of extant cats and their sabre-toothed relatives

[Background] The evolutionary relationships of Felidae during their Early-Middle Miocene radiation is contentious. Although the early common ancestors have been subsumed under the grade-group Pseudaelurus, this group is thought to be paraphyletic, including the early ancestors of both modern cats and extinct sabretooths. [Methods] Here, we sequenced a draft nuclear genome of Smilodon populator, dated to 13,182 ± 90 cal BP, making this the oldest palaeogenome from South America to date, a region known to be problematic for ancient DNA preservation. We analysed this genome, together with genomes from other extinct and extant cats to investigate their phylogenetic relationships. [Results] We confirm a deep divergence (~20.65 Ma) within sabre-toothed cats. Through the analysis of both simulated and empirical data, we show a lack of gene flow between Smilodon and contemporary Felidae. [Conclusions] Given that some species traditionally assigned to Pseudaelurus originated in the Early Miocene ~20 Ma, this indicates that some species of Pseudaelurus may be younger than the lineages they purportedly gave rise to, further supporting the hypothesis that Pseudaelurus was paraphyletic.This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No [681396]), (project Extinction Genomics). This project has also received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. FP7-PEOPLE-2011-IEF-298820. The work was also supported by the Independent Research Fund Denmark | Natural Sciences, Forskningsprojekt 1, grant no. 8021-00218B to EDL

Variability of the winter wind waves and swell in the North Atlantic and North Pacific as revealed by the Voluntary Observing Ship data

This paper analyses secular changes and interannual variability in the wind wave, swell, and significant wave height (SWH) characteristics over the North Atlantic and North Pacific on the basis of wind wave climatology derived from the visual wave observations of voluntary observing ship (VOS) officers. These data are available from the International Comprehensive Ocean–Atmosphere Data Set (ICOADS) collection of surface meteorological observations for 1958–2002, but require much more complicated preprocessing than standard meteorological variables such as sea level pressure, temperature, and wind. Visual VOS data allow for separate analysis of changes in wind sea and swell, as well as in significant wave height, which has been derived from wind sea and swell estimates. In both North Atlantic and North Pacific midlatitudes winter significant wave height shows a secular increase from 10 to 40 cm decade−1 during the last 45 yr. However, in the North Atlantic the patterns of trend changes for wind sea and swell are quite different from each other, showing opposite signs of changes in the northeast Atlantic. Trend patterns of wind sea, swell, and SWH in the North Pacific are more consistent with each other. Qualitatively the same conclusions hold for the analysis of interannual variability whose leading modes demonstrate noticeable differences for wind sea and swell. Statistical analysis shows that variability in wind sea is closely associated with the local wind speed, while swell changes can be driven by the variations in the cyclone counts, implying the importance of forcing frequency for the resulting changes in significant wave height. This mechanism of differences in variability patterns of wind sea and swell is likely more realistic than the northeastward propagation of swells from the regions from which the wind sea signal originates

On morphological hierarchical representations for image processing and spatial data clustering

Hierarchical data representations in the context of classi cation and data clustering were put forward during the fties. Recently, hierarchical image representations have gained renewed interest for segmentation purposes. In this paper, we briefly survey fundamental results on hierarchical clustering and then detail recent paradigms developed for the hierarchical representation of images in the framework of mathematical morphology: constrained connectivity and ultrametric watersheds. Constrained connectivity can be viewed as a way to constrain an initial hierarchy in such a way that a set of desired constraints are satis ed. The framework of ultrametric watersheds provides a generic scheme for computing any hierarchical connected clustering, in particular when such a hierarchy is constrained. The suitability of this framework for solving practical problems is illustrated with applications in remote sensing

Trait and phylogenetic diversity provide insights into community assembly of reef‐associated shrimps (Palaemonidae) at different spatial scales across the Chagos Archipelago

Coral reefs are the most biodiverse marine ecosystem and one of the most threatened by global climate change impacts. The vast majority of diversity on reefs is comprised of small invertebrates that live within the reef structure, termed the cryptofauna. This component of biodiversity is hugely understudied, and many species remain undescribed. This study represents a rare analysis of assembly processes structuring a distinct group of cryptofauna, the Palaemonidae, in the Chagos Archipelago, a reef ecosystem under minimal direct human impacts in the central Indian Ocean. The Palaemonidae are a diverse group of Caridae (infraorder of shrimps) that inhabit many different niches on coral reefs and are of particular interest because of their varied habitat associations. Phylogenetic and trait diversity and phylogenetic signal were used to infer likely drivers of community structure. The mechanisms driving palaemonid community assembly and maintenance in the Chagos Archipelago showed distinct spatial patterns. At local scales, among coral colonies and among reefs fringing individual atolls, significant trait, and phylogenetic clustering patterns suggest environmental filtering may be a dominant ecological process driving Palaemonidae community structure, although local competition through equalizing mechanisms may also play a role in shaping the local community structure. Importantly, we also tested the robustness of phylogenetic diversity to changes in evolutionary information as multi‐gene phylogenies are resource intensive and for large families, such as the Palaemonidae, are often incomplete. These tests demonstrated a very modest impact on phylogenetic community structure, with only one of the four genes (PEPCK gene) in the phylogeny affecting phylogenetic diversity patterns, which provides useful information for future studies on large families with incomplete phylogenies. These findings contribute to our limited knowledge of this component of biodiversity in a marine locality as close to undisturbed by humans as can be found. It also provides a rare evaluation of phylogenetic diversity methods