Sampling distributions and the bootstrap

The bootstrap can be used to assess uncertainty of sample estimates

Points of Significance: Statistics versus Machine Learning

International audienc

Update of the Anopheles gambiae PEST genome assembly

BACKGROUND: The genome of Anopheles gambiae, the major vector of malaria, was sequenced and assembled in 2002. This initial genome assembly and analysis made available to the scientific community was complicated by the presence of assembly issues, such as scaffolds with no chromosomal location, no sequence data for the Y chromosome, haplotype polymorphisms resulting in two different genome assemblies in limited regions and contaminating bacterial DNA. RESULTS: Polytene chromosome in situ hybridization with cDNA clones was used to place 15 unmapped scaffolds (sizes totaling 5.34 Mbp) in the pericentromeric regions of the chromosomes and oriented a further 9 scaffolds. Additional analysis by in situ hybridization of bacterial artificial chromosome (BAC) clones placed 1.32 Mbp (5 scaffolds) in the physical gaps between scaffolds on euchromatic parts of the chromosomes. The Y chromosome sequence information (0.18 Mbp) remains highly incomplete and fragmented among 55 short scaffolds. Analysis of BAC end sequences showed that 22 inter-scaffold gaps were spanned by BAC clones. Unmapped scaffolds were also aligned to the chromosome assemblies in silico, identifying regions totaling 8.18 Mbp (144 scaffolds) that are probably represented in the genome project by two alternative assemblies. An additional 3.53 Mbp of alternative assembly was identified within mapped scaffolds. Scaffolds comprising 1.97 Mbp (679 small scaffolds) were identified as probably derived from contaminating bacterial DNA. In total, about 33% of previously unmapped sequences were placed on the chromosomes. CONCLUSION: This study has used new approaches to improve the physical map and assembly of the A. gambiae genome

MISTIC: mutual information server to infer coevolution

MISTIC (mutual information server to infer coevolution) is a web server for graphical representation of the information contained within a MSA (multiple sequence alignment) and a complete analysis tool for Mutual Information networks in protein families. The server outputs a graphical visualization of several information-related quantities using a circos representation. This provides an integrated view of the MSA in terms of (i) the mutual information (MI) between residue pairs, (ii) sequence conservation and (iii) the residue cumulative and proximity MI scores. Further, an interactive interface to explore and characterize the MI network is provided. Several tools are offered for selecting subsets of nodes from the network for visualization. Node coloring can be set to match different attributes, such as conservation, cumulative MI, proximity MI and secondary structure. Finally, a zip file containing all results can be downloaded. The server is available at http://mistic.leloir.org.ar. In summary, MISTIC allows for a comprehensive, compact, visually rich view of the information contained within an MSA in a manner unique to any other publicly available web server. In particular, the use of circos representation of MI networks and the visualization of the cumulative MI and proximity MI concepts is novel.Fil: Simonetti, Franco Lucio. Fundación Instituto Leloir. Unidad de Bioinformática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Teppa, Elin. Fundación Instituto Leloir. Unidad de Bioinformática; ArgentinaFil: Chernomoretz, Ariel. Fundación Instituto Leloir. Unidad de Bioinformática; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; ArgentinaFil: Nielsen, Morten. Technical University of Denmark. Center for Biological Sequence Analysis; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Marino Buslje, Cristina . Fundación Instituto Leloir. Unidad de Bioinformática; Argentin

Förderung des Transfers materialwissenschaftlicher Forschungsergebnisse hin zur Markteinführung durch ein strukturiertes Rahmenprogramm zur interdisziplinären Kompetenzaneignung und Demonstrator-Entwicklung: eine Fallstudie

Das vorliegende Paper beschreibt ein Vorgehen zur Förderung des Transfers materialwissenschaftlicher Forschungsergebnisse hin zur Marktfähigkeit durch ein strukturiertes Rahmenprogramm zur Kompetenzaneignung und zur interdisziplinären kollaborativen Demonstrator-Entwicklung anhand eines Fallbeispiels. Das Rahmenprogramm dient der Vermittlung von Kompetenzen aus Design und Geschäftsmodellentwicklung zur Überwindung des „Valley of Death“, also des scheiternden Transfers von Forschungsergebnissen hin zur Marktreife. Es werden Methodik und Vorgehen im Vorhaben betrachtet. Darüber hinaus werden die observierten Limitationen beschrieben, die bei der Arbeit mit den Methoden beobachtet wurden und das Feld noch weiter einschränken. Die Ergebnisse wurden auf Basis von a) Literaturanalysen, b) einer Umfrage unter Materialwissenschaftlern und c) Beobachtungen bei der Konzeption, Durchführung und Auswertung von Trainings im „Material Demo Lab“ bewertet. Zu den Kernerkenntnissen gehört, die gesteigerte Akzeptanz der neu erlernten Methoden, wenn diese vorrangig die Technologieentwicklung vor dem Hintergrund der Geschäftsmodellentwicklung adressieren. Die Entwicklung eines Technologiedemonstrators wurde als treibende Kraft und Motivationsgeber im beschriebenen Rahmenprogramm identifiziert

PIMMS (Pragmatic Insertional Mutation Mapping System) laboratory methodology a readily accessible tool for identification of essential genes in Streptococcus

The Pragmatic Insertional Mutation Mapping (PIMMS) laboratory protocol was developed alongside various bioinformatics packages (Blanchard et al., 2015) to enable detection of essential and conditionally essential genes in Streptococcus and related bacteria. This extended the methodology commonly used to locate insertional mutations in individual mutants to the analysis of mutations in populations of bacteria. In Streptococcus uberis, a pyogenic Streptococcus associated with intramammary infection and mastitis in ruminants, the mutagen pGhost9:ISS1 was shown to integrate across the entire genome. Analysis of >80,000 mutations revealed 196 coding sequences, which were not be mutated and a further 67 where mutation only occurred beyond the 90th percentile of the coding sequence. These sequences showed good concordance with sequences within the database of essential genes and typically matched sequences known to be associated with basic cellular functions. Due to the broad utility of this mutagen and the simplicity of the methodology it is anticipated that PIMMS will be of value to a wide range of laboratories in functional genomic analysis of a wide range of Gram positive bacteria (Streptococcus, Enterococcus, and Lactococcus) of medical, veterinary, and industrial significance

The complex intron landscape and massive intron invasion in a picoeukaryote provides insights into intron evolution

Genes in pieces and spliceosomal introns are a landmark of eukaryotes, with intron invasion usually assumed to have happened early on in evolution. Here, we analyse the intron landscape of Micromonas, a unicellular green alga in the Mamiellophyceae lineage, demonstrating the co-existence of several classes of introns and the occurrence of recent massive intron invasion. This study focuses on two strains, CCMP1545 and RCC299, and their related individuals from ocean samplings, showing that they not only harbour different classes of introns depending on their location in the genome, as for other Mamiellophyceae, but uniquely carry several classes of repeat introns. These introns, dubbed introner elements (IEs), are found at novel positions in genes and have conserved sequences, contrary to canonical introns. This IE invasion has a huge impact on the genome, doubling the number of introns in the CCMP1545 strain. We hypothesize that each IE class originated from a single ancestral IE that has been colonizing the genome after strain divergence by inserting copies of itself into genes by intron transposition, likely involving reverse splicing. Along with similar cases recently observed in other organisms, our observations in Micromonas strains shed a new light on the evolution of introns, suggesting that intron gain is more widespread than previously thought

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

Phylogenomic approaches to DNA barcoding of herbal medicines: developing clade-specific diagnostic characters for Berberis

DNA barcoding of herbal medicines has been mainly concerned with authentication of products in trade and has raised awareness of species substitution and adulteration. More recently DNA barcodes have been included in pharmacopoeias, providing tools for regulatory purposes. The commonly used DNA barcoding regions in plants often fail to resolve identification to species level. This can be especially challenging in evolutionarily complex groups where incipient or reticulate speciation is ongoing. In this study, we take a phylogenomic approach, analyzing whole plastid sequences from the evolutionarily complex genus Berberis in order to develop DNA barcodes for the medicinally important species B. aristata. The phylogeny reconstructed from an alignment of ~160k bp of chloroplast DNA for 57 species reveals that the pharmacopoeial species in question is polyphyletic, complicating development of a species-specific DNA barcode. Instead we propose a DNA barcode that is clade specific, using our phylogeny to define Operational Phylogenetic Units (OPUs). The plastid alignment is then reduced to small, informative DNA regions including nucleotides diagnostic for these OPUs. These DNA barcodes were tested on commercial samples, and shown to discriminate plants in trade and therefore to meet the requirement of a pharmacopoeial standard. The proposed method provides an innovative approach for inferring DNA barcodes for evolutionarily complex groups for regulatory purposes and quality control