Haplotype-aware graph indexes

The variation graph toolkit (VG) represents genetic variation as a graph. Each path in the graph is a potential haplotype, though most paths are unlikely recombinations of true haplotypes. We augment the VG model with haplotype information to identify which paths are more likely to be correct. For this purpose, we develop a scalable implementation of the graph extension of the positional Burrows-Wheeler transform. We demonstrate the scalability of the new implementation by indexing the 1000 Genomes Project haplotypes. We also develop an algorithm for simplifying variation graphs for k-mer indexing without losing any k-mers in the haplotypes

Haplotype-aware graph indexes.

MOTIVATION: The variation graph toolkit (VG) represents genetic variation as a graph. Although each path in the graph is a potential haplotype, most paths are non-biological, unlikely recombinations of true haplotypes. RESULTS: We augment the VG model with haplotype information to identify which paths are more likely to exist in nature. For this purpose, we develop a scalable implementation of the graph extension of the positional Burrows-Wheeler transform. We demonstrate the scalability of the new implementation by building a whole-genome index of the 5008 haplotypes of the 1000 Genomes Project, and an index of all 108 070 Trans-Omics for Precision Medicine Freeze 5 chromosome 17 haplotypes. We also develop an algorithm for simplifying variation graphs for k-mer indexing without losing any k-mers in the haplotypes. AVAILABILITY AND IMPLEMENTATION: Our software is available at https://github.com/vgteam/vg, https://github.com/jltsiren/gbwt and https://github.com/jltsiren/gcsa2. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Effect of dipolar interactions on the magnetization of a cubic array of nanomagnets

We investigated the effect of intermolecular dipolar interactions on a cubic 3D ensemble of 5X5X4=100 nanomagnets, each with spin $S = 5$. We employed the Landau-Lifshitz-Gilbert equation to solve for the magnetization $M(B)$ curves for several values of the damping constant $\alpha$, the induction sweep rate, the lattice constant $a$, the temperature $T$, and the magnetic anisotropy field $H_A$. We find that the smaller the $\alpha$, the stronger the maximum induction required to produce hysteresis. The shape of the hysteresis loops also depends on the damping constant. We find further that the system magnetizes and demagnetizes at decreasing magnetic field strengths with decreasing sweep rates, resulting in smaller hysteresis loops. Variations of $a$ within realistic values (1.5 nm - 2.5 nm) show that the dipolar interaction plays an important role in the magnetic hysteresis by controlling the relaxation process. The $T$ dependencies of $\alpha$ and of $M$ are presented and discussed with regard to recent experimental data on nanomagnets. $H_A$ enhances the size of the hysteresis loops for external fields parallel to the anisotropy axis, but decreases it for perpendicular external fields. Finally, we reproduce and test an $M(B)$ curve for a 2D-system [M. Kayali and W. Saslow, Phys. Rev. B {\bf 70}, 174404 (2004)]. We show that its hysteretic behavior is only weakly dependent on the shape anisotropy field and the sweep rate, but depends sensitively upon the dipolar interactions. Although in 3D systems, dipole-dipole interactions generally diminish the hysteresis, in 2D systems, they strongly enhance it. For both square 2D and rectangular 3D lattices with ${\bm B}||(\hat{\bm x}+\hat{\bm y})$, dipole-dipole interactions can cause large jumps in the magnetization.Comment: 15 pages 14 figures, submitted to Phys. Rev.

Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease

Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena, right pallidum, right thalamus, cerebellum, middle frontal, middle occipital, right superior and left inferior temporal gyri, and left superior parietal lobule. The modulated happiness network included postcentral gyri, left caudate, right cingulate cortex, right superior and inferior parietal lobules, and right superior frontal, middle temporal, middle occipital and precentral gyri. These effects were not driven merely by striatal dysfunction. We did not find equivalent associations between brain structure and emotion recognition, and the pre-manifest Huntington's disease cohort did not have a behavioural deficit in out-of-scanner emotion recognition relative to controls. In addition, we found increased neural activity in the pre-manifest subjects in response to all three emotions in frontal regions, predominantly in the middle frontal gyri. Overall, these findings suggest that pathophysiological effects of Huntington's disease may precede the development of overt clinical symptoms and detectable cerebral atroph

SOFIA and ALMA Investigate Magnetic Fields and Gas Structures in Massive Star Formation: The Case of the Masquerading Monster in BYF 73

We present SOFIA+ALMA continuum and spectral-line polarisation data on the massive molecular cloud BYF 73, revealing important details about the magnetic field morphology, gas structures, and energetics in this unusual massive star formation laboratory. The 154$\mu$m HAWC+ polarisation map finds a highly organised magnetic field in the densest, inner 0.55$\times$0.40 pc portion of the cloud, compared to an unremarkable morphology in the cloud's outer layers. The 3mm continuum ALMA polarisation data reveal several more structures in the inner domain, including a pc-long, $\sim$500 M$_{\odot}$ "Streamer" around the central massive protostellar object MIR 2, with magnetic fields mostly parallel to the east-west Streamer but oriented north-south across MIR 2. The magnetic field orientation changes from mostly parallel to the column density structures to mostly perpendicular, at thresholds $N_{\rm crit}$ = 6.6$\times$10$^{26}$ m$^{-2}$, $n_{\rm crit}$ = 2.5$\times$10$^{11}$ m$^{-3}$, and $B_{\rm crit}$ = 42$\pm$7 nT. ALMA also mapped Goldreich-Kylafis polarisation in $^{12}$CO across the cloud, which traces in both total intensity and polarised flux, a powerful bipolar outflow from MIR 2 that interacts strongly with the Streamer. The magnetic field is also strongly aligned along the outflow direction; energetically, it may dominate the outflow near MIR 2, comprising rare evidence for a magnetocentrifugal origin to such outflows. A portion of the Streamer may be in Keplerian rotation around MIR 2, implying a gravitating mass 1350$\pm$50 M$_{\odot}$ for the protostar+disk+envelope; alternatively, these kinematics can be explained by gas in free fall towards a 950$\pm$35 M$_{\odot}$ object. The high accretion rate onto MIR 2 apparently occurs through the Streamer/disk, and could account for $\sim$33% of MIR 2's total luminosity via gravitational energy release.Comment: 33 pages, 32 figures, accepted by ApJ. Line-Integral Convolution (LIC) images and movie versions of Figures 3b, 7, and 29 are available at https://gemelli.spacescience.org/~pbarnes/research/champ/papers

West Nile Virus Detection in American Crows

A dipstick immunochromatographic assay used for West Nile virus (WNV) detection in mosquitoes was investigated for application to testing of fecal, saliva, and tissue samples from dead American Crows (Corvus brachyrhynchos). Results suggest that VecTest may be an efficient method for WNV detection in field-collected, dead American Crows, although confirmation of results and further investigation are warranted

West Nile Virus Detection in American Crows

A dipstick immunochromatographic assay used for West Nile virus (WNV) detection in mosquitoes was investigated for application to testing of fecal, saliva, and tissue samples from dead American Crows (Corvus brachyrhynchos). Results suggest that VecTest may be an efficient method for WNV detection in field-collected, dead American Crows, although confirmation of results and further investigation are warranted

THE MAGNETIC FIELD MORPHOLOGY OF THE CLASS 0 PROTOSTAR L1157-mm

We present the first detection of polarization around the Class 0 low-mass protostar L1157-mm at two different wavelengths. We show polarimetric maps at large scales (10 '' resolution at 350 mu m) from the SHARC-II Polarimeter and at smaller scales (1.'' 2-4.'' 5 at 1.3 mm) from the Combined Array for Research in Millimeter-wave Astronomy (CARMA). The observations are consistent with each other and show inferred magnetic field lines aligned with the outflow. The CARMA observations suggest a full hourglass magnetic field morphology centered about the core; this is only the second well-defined hourglass detected around a low-mass protostar to date. We apply two different methods to CARMA polarimetric observations to estimate the plane-of-sky magnetic field magnitude, finding values of 1.4 and 3.4 mG.</p

Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in the HIV Outpatient Study: 1999–2008

Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT) in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS) who, during 1999–2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI) was defined as triple-class exposure (TCE). Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999–2008 (88% to 79%, P = 0.05). Resistance to PIs decreased among PI-exposed patients (71% to 46%, P = 0.010) as exposure to ritonavir-boosted PIs increased (6% to 81%, P < 0.001). Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%), and triple-class-resistance among TCE patients (66% to 41%), but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999–2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs