Haplotype inference based on Hidden Markov Models in the QTL-MAS 2010 multi-generational dataset

<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated an approach for efficient computation of genotype probabilities, and more generally probabilities of allele inheritance in inbred as well as outbred populations. That work also included an extension for haplotype inference, or phasing, using Hidden Markov Models. Computational phasing of multi-thousand marker datasets has not become common as of yet. In this communication, we further investigate the method presented earlier for such problems, in a multi-generational dataset simulated for QTL detection.</p> <p>Results</p> <p>When analyzing the dataset simulated for the 14th QTLMAS workshop, the phasing produced showed zero deviations compared to original simulated phase in the founder generation. In total, 99.93% of all markers were correctly phased. 97.68% of the individuals were correct in all markers over all 5 simulated chromosomes. Results were produced over a weekend on a small computational cluster. The specific algorithmic adaptations needed for the Markov model training approach in order to reach convergence are described.</p> <p>Conclusions</p> <p>Our method provides efficient, near-perfect haplotype inference allowing the determination of completely phased genomes in dense pedigrees. These developments are of special value for applications where marker alleles are not corresponding directly to QTL alleles, thus necessitating tracking of allele origin, and in complex multi-generational crosses. The cnF2freq codebase, which is in a current state of active development, is available under a BSD-style license.</p

Imputation of Single Nucleotide Polymorphism Genotypes in Biparental, Backcross, and Topcross Populations with a Hidden Markov Model

Genomic selection offers great potential to increase the rate of genetic improvement in plant breeding programs. The ability to accurately impute missing genotypes for a large number of individuals, screened with low marker density, at low cost is crucial for achieving this. In this research an existing general algorithm for tracing allele inheritance in known pedigrees was modified to enable genotype imputation in specific crosses (biparental, backcross, and topcross) that are common in plant breeding. The extension was tested with a series of representative simulated examples of these crosses. The results show success of imputation is affected by many factors including the number of low-density markers per cM, level of inbreeding or intercrossing of the individuals to have genotypes imputed, level of inbreeding of the parents of a cross, and genome length; but not by the number of high-density markers or by the interaction between the genome length and the number of low-density markers. With as few as one or two markers per 20 cM genotype imputation was successful when parents were inbred. Therefore, genotyping strategies in which inbred parents of a cross are genotyped at high-density and their descendants are genotyped with 200 to 400 markers genome wide may be cost effective and useful in practical plant breeding programs that utilize genomic selection

A statistical approach to detect protein complexes at X-ray free electron laser facilities

The Flash X-ray Imaging (FXI) technique, under development at X-ray free electron lasers (XFEL), aims to achieve structure determination based on diffraction from individual macromolecular complexes. We report an FXI study on the first protein complex-RNA polymerase II-ever injected at an XFEL. A successful 3D reconstruction requires a high number of observations of the sample in various orientations. The measured diffraction signal for many shots can be comparable to background. Here we present a robust and highly sensitive hit-identification method based on automated modeling of beamline background through photon statistics. It can operate at controlled false positive hit-rate of 3 x10(-5). We demonstrate its power in determining particle hits and validate our findings against an independent hit-identification approach based on ion time-of-flight spectra. We also validate the advantages of our method over simpler hit-identification schemes via tests on other samples and using computer simulations, showing a doubled hit-identification power

Coherent diffraction of single Rice Dwarf virus particles using hard X-rays at the Linac Coherent Light Source

Single particle diffractive imaging data from Rice Dwarf Virus (RDV) were recorded using the Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS). RDV was chosen as it is a wellcharacterized model system, useful for proof-of-principle experiments, system optimization and algorithm development. RDV, an icosahedral virus of about 70 nm in diameter, was aerosolized and injected into the approximately 0.1 mu m diameter focused hard X-ray beam at the CXI instrument of LCLS. Diffraction patterns from RDV with signal to 5.9 angstrom ngstrom were recorded. The diffraction data are available through the Coherent X-ray Imaging Data Bank (CXIDB) as a resource for algorithm development, the contents of which are described here.11Ysciescopu

Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser

Citation: Ekeberg, T., Svenda, M., Abergel, C., Maia, F., Seltzer, V., Claverie, J. M., . . . Hajdu, J. (2015). Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser. Physical Review Letters, 114(9), 6. doi:10.1103/PhysRevLett.114.098102We present a proof-of-concept three-dimensional reconstruction of the giant mimivirus particle from experimentally measured diffraction patterns from an x-ray free-electron laser. Three-dimensional imaging requires the assembly of many two-dimensional patterns into an internally consistent Fourier volume. Since each particle is randomly oriented when exposed to the x-ray pulse, relative orientations have to be retrieved from the diffraction data alone. We achieve this with a modified version of the expand, maximize and compress algorithm and validate our result using new methods.Additional Authors: Andersson, I.;Loh, N. D.;Martin, A. V.;Chapman, H.;Bostedt, C.;Bozek, J. D.;Ferguson, K. R.;Krzywinski, J.;Epp, S. W.;Rolles, D.;Rudenko, A.;Hartmann, R.;Kimmel, N.;Hajdu, J

Three-dimensional reconstruction of the giant mimivirus particle with an X-ray free-electron laser

10.1103/PhysRevLett.114.098102Physical Review Letters114909810

Intergenerational impacts of maternal mortality: Qualitative findings from rural Malawi

Background: Maternal mortality, although largely preventable, remains unacceptably high in developing countries such as Malawi and creates a number of intergenerational impacts. Few studies have investigated the far-reaching impacts of maternal death beyond infant survival. This study demonstrates the short- and long-term impacts of maternal death on children, families, and the community in order to raise awareness of the true costs of maternal mortality and poor maternal health care in Neno, a rural and remote district in Malawi. Methods: Qualitative in-depth interviews were conducted to assess the impact of maternal mortality on child, family, and community well-being. We conducted 20 key informant interviews, 20 stakeholder interviews, and six sex-stratified focus group discussions in the seven health centers that cover the district. Transcripts were translated, coded, and analyzed in NVivo 10. Results: Participants noted a number of far-reaching impacts on orphaned children, their new caretakers, and extended families following a maternal death. Female relatives typically took on caregiving responsibilities for orphaned children, regardless of the accompanying financial hardship and frequent lack of familial or governmental support. Maternal death exacerbated children’s vulnerabilities to long-term health and social impacts related to nutrition, education, employment, early partnership, pregnancy, and caretaking. Impacts were particularly salient for female children who were often forced to take on the majority of the household responsibilities. Participants cited a number of barriers to accessing quality child health care or support services, and many were unaware of programming available to assist them in raising orphaned children or how to access these services. Conclusions: In order to both reduce preventable maternal mortality and diminish the impacts on children, extended families, and communities, our findings highlight the importance of financing and implementing universal access to emergency obstetric and neonatal care, and contraception, as well as social protection programs, including among remote populations