A bioinformatic analysis of malaria host and pathogen genomics

Malaria is a significant global disease caused by infection with parasites of the Plasmodium genus, which resulted in an estimated 216 million cases and 445,000 deaths in 2016 alone. Co-evolution of Plasmodium parasites and their human hosts has shaped both genomes for thousands of years. In this thesis I describe my work identifying and characterising novel genomic variants and selection signals associated with host-pathogen interactions in malaria. For the parasite, analysis of the impact of sustained sulfadoxine/pyrimethamine (SP) use on the Malawian parasite population (n=220) lead to the identification of selection signals associated with SP resistance factors and a novel 436 bp gch1 promoter region duplication at near-fixation. Next a global approach to copy number variation discovery (n=3,110), based on short read sequencing, identified several novel and geographically specific variants including large 22.9 kbp duplications of crt in West Africa. Finally, an inversion discovery pipeline was developed for a long read based approach to inversion detection (n=17). This led to the identification of a novel ‘sandwich inversion’ of pi4k in a sample of GB4, similar to inversion-duplication of gch1 in Dd2. For human genetics within the context of malaria, I conducted a GWAS with a Tanzanian dataset (n=914) and identified novel protective associations, such as for IL-23R and IL-12RBR2. I also identified novel structural variants (SV) with a short-read sequencing based dataset of Tanzanian parent-child trios (n=234) identifying several novel SVs associated with blood antigen systems. Near-fixation deletions in SEC22B and BET1L were also identified, suggesting an impact on intracellular transportation. Genomic variation associated with host-pathogen interactions is diverse, and SVs represent one overlooked aspect that requires further investigation. Bioinformatic approaches can help identify novel variants but depend upon novel software development, such as those described within this thesis (e.g. SV-Pop)

Neutron Drops and Skyrme Energy-Density Functionals

The J$^{\pi}$=0$^+$ ground state of a drop of 8 neutrons and the lowest 1/2$^-$ and 3/2$^-$ states of 7-neutron drops, all in an external well, are computed accurately with variational and Green's function Monte Carlo methods for a Hamiltonian containing the Argonne $v_{18}$ two-nucleon and Urbana IX three-nucleon potentials. These states are also calculated using Skyrme-type energy-density functionals. Commonly used functionals overestimate the central density of these drops and the spin-orbit splitting of 7-neutron drops. Improvements in the functionals are suggested

Direct Urca Process in a Neutron Star Mantle

We show that the direct Urca process of neutrino emission is allowed in two possible phases of nonspherical nuclei (inverse cylinders and inverse spheres) in the mantle of a neutron star near the crust-core interface. The process is open because neutrons and protons move in a periodic potential created by inhomogeneous nuclear structures. In this way the nucleons acquire large quasimomenta needed to satisfy momentum-conservation in the neutrino reaction. The appropriate neutrino emissivity in a nonsuperfluid matter is about 2--3 orders of magnitude higher than the emissivity of the modified Urca process in the stellar core. The process may noticeably accelerate the cooling of low-mass neutron stars.Comment: 7 pages, 3 figures, submitted to A&

A survey of the parameter space of the compressible liquid drop model as applied to the neutron star inner crust

We present a systematic survey the range of predictions of the neutron star inner crust composition, crust-core transition densities and pressures, and density range of the nuclear `pasta' phases at the bottom of the crust provided by the compressible liquid drop model in the light of current experimental and theoretical constraints on model parameters. Using a Skyrme-like model for nuclear matter, we construct baseline sequences of crust models by consistently varying the density dependence of the bulk symmetry energy at nuclear saturation density, $L$, under two conditions: (i) that the magnitude of the symmetry energy at saturation density $J$ is held constant, and (ii) $J$ correlates with $L$ under the constraint that the pure neutron matter (PNM) EoS satisfies the results of ab-initio calculations at low densities. Such baseline crust models facilitate consistent exploration of the $L$ dependence of crustal properties. The remaining surface energy and symmetric nuclear matter parameters are systematically varied around the baseline, and different functional forms of the PNM EoS at sub-saturation densities implemented, to estimate theoretical `error bars' for the baseline predictions. Inner crust composition and transition densities are shown to be most sensitive to the surface energy at very low proton fractions and to the behavior of the sub-saturation PNM EoS. Recent calculations of the energies of neutron drops suggest that the low-proton-fraction surface energy might be higher than predicted in Skyrme-like models, which our study suggests may result in a greatly reduced volume of pasta in the crust than conventionally predicted.Comment: 37 Pages, 16 figures, accepted for publication in Astrophysical Journal Supplement Serie

Mixed quark-nucleon phase in neutron stars and nuclear symmetry energy

The influence of the nuclear symmetry energy on the formation of a mixed quark-nucleon phase in neutron star cores is studied. We use simple parametrizations of the nuclear matter equation of state, and the bag model for the quark phase. The behavior of nucleon matter isobars, which is responsible for the existence of the mixed phase, is investigated. The role of the nuclear symmetry energy changes with the value of the bag constant B. For lower values of B the properties of the mixed phase do not depend strongly on the symmetry energy. For larger B we find that a critical pressure for the first quark droplets to form is strongly dependent on the nuclear symmetry energy, but the pressure at which last nucleons disappear is independent of it.Comment: 12 pages, 16 figures, Phys. Rev. C in pres

The Minimal CFL-Nuclear Interface

At nuclear matter density, electrically neutral strongly interacting matter in weak equilibrium is made of neutrons, protons and electrons. At sufficiently high density, such matter is made of up, down and strange quarks in the color-flavor locked phase, with no electrons. As a function of increasing density (or, perhaps, increasing depth in a compact star) other phases may intervene between these two phases which are guaranteed to be present. The simplest possibility, however, is a single first order phase transition between CFL and nuclear matter. Such a transition, in space, could take place either through a mixed phase region or at a single sharp interface with electron-free CFL and electron-rich nuclear matter in stable contact. Here we construct a model for such an interface. It is characterized by a region of separated charge, similar to an inversion layer at a metal-insulator boundary. On the CFL side, the charged boundary layer is dominated by a condensate of negative kaons. We then consider the energetics of the mixed phase alternative. We find that the mixed phase will occur only if the nuclear-CFL surface tension is significantly smaller than dimensional analysis would indicate.Comment: 30 pages, 7 figure

Upper limits on the observational effects of nuclear pasta in neutron stars

The effects of the existence of exotic nuclear shapes at the bottom of the neutron star inner crust - nuclear `pasta' - on observational phenomena are estimated by comparing the limiting cases that those phases have a vanishing shear modulus and that they have the shear modulus of a crystalline solid . We estimate the effect on torsional crustal vibrations and on the maximum quadrupole ellipticity sustainable by the crust. The crust composition and transition densities are calculated consistently with the global properties, using a liquid drop model with a bulk nuclear equation of state (EoS) which allows a systematic variation of the nuclear symmetry energy. The symmetry energy J and its density dependence L at nuclear saturation density are the dominant nuclear inputs which determine the thickness of the crust, the range of densities at which pasta might appear, as well as global properties such as the radius and moment of inertia. We show the importance of calculating the global neutron star properties on the same footing as the crust EoS, and demonstrate that in the range of experimentally acceptable values of L, the pasta phase can alter the crust frequencies by up to a factor of three, exceeding the effects of superfluidity on the crust modes, and decrease the maximum quadrupole ellipticity sustainable by the crust by up to an order of magnitude. The signature of the pasta phases and the density dependence of the symmetry energy on the potential observables highlights the possibility of constraining the EoS of dense, neutron-rich matter and the properties of the pasta phases using astrophysical observations.Comment: 8 pages, 7 figures, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Partial Homology Relations - Satisfiability in terms of Di-Cographs

Directed cographs (di-cographs) play a crucial role in the reconstruction of evolutionary histories of genes based on homology relations which are binary relations between genes. A variety of methods based on pairwise sequence comparisons can be used to infer such homology relations (e.g.\ orthology, paralogy, xenology). They are \emph{satisfiable} if the relations can be explained by an event-labeled gene tree, i.e., they can simultaneously co-exist in an evolutionary history of the underlying genes. Every gene tree is equivalently interpreted as a so-called cotree that entirely encodes the structure of a di-cograph. Thus, satisfiable homology relations must necessarily form a di-cograph. The inferred homology relations might not cover each pair of genes and thus, provide only partial knowledge on the full set of homology relations. Moreover, for particular pairs of genes, it might be known with a high degree of certainty that they are not orthologs (resp.\ paralogs, xenologs) which yields forbidden pairs of genes. Motivated by this observation, we characterize (partial) satisfiable homology relations with or without forbidden gene pairs, provide a quadratic-time algorithm for their recognition and for the computation of a cotree that explains the given relations

Microscopic Study of Slablike and Rodlike Nuclei: Quantum Molecular Dynamics Approach

Structure of cold dense matter at subnuclear densities is investigated by quantum molecular dynamics (QMD) simulations. We succeeded in showing that the phases with slab-like and rod-like nuclei etc. can be formed dynamically from hot uniform nuclear matter without any assumptions on nuclear shape. We also observe intermediate phases, which has complicated nuclear shapes. Geometrical structures of matter are analyzed with Minkowski functionals, and it is found out that intermediate phases can be characterized as ones with negative Euler characteristic. Our result suggests the existence of these kinds of phases in addition to the simple ``pasta'' phases in neutron star crusts.Comment: 6 pages, 4 figures, RevTex4; to be published in Phys. Rev. C Rapid Communication (accepted version

First Order Kaon Condensation in Neutron Stars: Finite Size Effects in the Mixed Phase

We study the role of Coulomb and surface effects on the phase transition from dense nuclear matter to a mixed phase of nuclear and kaon-condensed matter. We calculate corrections to the bulk calculation of the equation of state (EOS) and the critical density for the transition by solving explicitly for spherical, cylindrical, and planar structures. The importance of Debye screening in the determination of the charged particle profiles is studied in some detail. We find that the surface and Coulomb contributions to the energy density are small, but that they play an important role in the determination of the critical pressure for the transition, as well as affecting the size and geometry of favored structures. This changes the EOS over a wide range of pressure and consequently increases the maximum mass by about 0.1 solar masses. Implications for transport properties of the mixed phase are also discussed.Comment: 18 pages, 6 figure