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

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

Antibody Prevalence of West Nile Virus in Birds, Illinois, 2002

Antibodies to West Nile virus were detected in 94 of 1,784 Illinois birds during 2002. Captive and urban birds had higher seropositivity than did birds from natural areas, and northern and central Illinois birds’ seropositivity was greater than that from birds from the southern sites. Adult and hatch-year exposure rates did not differ significantly

Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract

The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity

Genotyping structural variants in pangenome graphs using the vg toolkit.

Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmark vg against state-of-the-art SV genotypers using three sequence-resolved SV catalogs generated by recent long-read sequencing studies. In addition, we use assemblies from 12 yeast strains to show that graphs constructed directly from aligned de novo assemblies improve genotyping compared to graphs built from intermediate SV catalogs in the VCF format

Compartmental Genomics in Living Cells Revealed by Single-Cell Nanobiopsy

The ability to study the molecular biology of living single cells in heterogeneous cell populations is essential for next generation analysis of cellular circuitry and function. Here, we developed a single-cell nanobiopsy platform based on scanning ion conductance microscopy (SICM) for continuous sampling of intracellular content from individual cells. The nanobiopsy platform uses electrowetting within a nanopipette to extract cellular material from living cells with minimal disruption of the cellular milieu. We demonstrate the subcellular resolution of the nanobiopsy platform by isolating small subpopulations of mitochondria from single living cells, and quantify mutant mitochondrial genomes in those single cells with high throughput sequencing technology. These findings may provide the foundation for dynamic subcellular genomic analysis

Search for Anomalous Couplings in the Higgs Sector at LEP

Anomalous couplings of the Higgs boson are searched for through the processes e^+ e^- -> H gamma, e^+ e^- -> e^+ e^- H and e^+ e^- -> HZ. The mass range 70 GeV < m_H < 190 GeV is explored using 602 pb^-1 of integrated luminosity collected with the L3 detector at LEP at centre-of-mass energies sqrt(s)=189-209 GeV. The Higgs decay channels H -> ffbar, H -> gamma gamma, H -> Z\gamma and H -> WW^(*) are considered and no evidence is found for anomalous Higgs production or decay. Limits on the anomalous couplings d, db, Delta(g1z), Delta(kappa_gamma) and xi^2 are derived as well as limits on the H -> gamma gamma and H -> Z gamma decay rates

Study of Inclusive Strange-Baryon Production and Search for Pentaquarks in Two-Photon Collisions at LEP

Measurements of inclusive production of the Lambda, Xi- and Xi*(1530) baryons in two-photon collisions with the L3 detector at LEP are presented. The inclusive differential cross sections for Lambda and Xi- are measured as a function of the baryon transverse momentum, pt, and pseudo-rapidity, eta. The mean number of Lambda, Xi- and Xi*(1530) baryons per hadronic two-photon event is determined in the kinematic range 0.4 GeV < pt< 2.5 GeV, |eta| < 1.2. Overall agreement with the theoretical models and Monte Carlo predictions is observed. A search for inclusive production of the pentaquark theta+(1540) in two-photon collisions through the decay theta+ -> proton K0s is also presented. No evidence for production of this state is found