The first near-complete assembly of the hexaploid bread wheat genome, Triticum aestivum, bioRxiv, 2017-07-04
AbstractCommon bread wheat, Triticum aestivum, has one of the most complex genomes known to science, with 6 copies of each chromosome, enormous numbers of near-identical sequences scattered throughout, and an overall size of more than 15 billion bases. Multiple past attempts to assemble the genome have failed. Here we report the first successful assembly of T. aestivum, using deep sequencing coverage from a combination of short Illumina reads and very long Pacific Biosciences reads. The final assembly contains 15,344,693,583 bases and has a weighted average (N50) contig size of of 232,659 bases. This represents by far the most complete and contiguous assembly of the wheat genome to date, providing a strong foundation for future genetic studies of this important food crop. We also report how we used the recently published genome of Aegilops tauschii, the diploid ancestor of the wheat D genome, to identify 4,179,762,575 bp of T. aestivum that correspond to its D genome components.
biorxiv genomics 200-500-users 2017NanoJ-SQUIRREL quantitative mapping and minimisation of super-resolution optical imaging artefacts, bioRxiv, 2017-07-03
Most super-resolution microscopy methods depend on steps that contribute to the formation of image artefacts. Here we present NanoJ-SQUIRREL, an ImageJ-based analytical approach providing a quantitative assessment of super-resolution image quality. By comparing diffraction-limited images and super-resolution equivalents of the same focal volume, this approach generates a quantitative map of super-resolution defects, as well as methods for their correction. To illustrate its broad applicability to super-resolution approaches we apply our method to Localization Microscopy, STED and SIM images of a variety of in-cell structures including microtubules, poxviruses, neuronal actin rings and clathrin coated pits. We particularly focus on single-molecule localisation microscopy, where super-resolution reconstructions often feature imperfections not present in the original data. By showing the quantitative evolution of data quality over these varied sample preparation, acquisition and super-resolution methods we display the potential of NanoJ-SQUIRREL to guide optimization of superresolution imaging parameters.
biorxiv biophysics 100-200-users 2017A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids, bioRxiv, 2017-06-29
AbstractThere is increasing interest in developing 3D tumor organoid models for drug development and personalized medicine applications. While tumor organoids are in principle amenable to high-throughput drug screenings, progress has been hampered by technical constraints and extensive manipulations required by current methodologies. Here, we introduce a miniaturized, fully automatable, flexible high-throughput method using a simplified geometry to rapidly establish 3D organoids from cell lines and primary tissue and robustly assay drug responses. As proof of principle, we use our miniring approach to establish organoids of high-grade serous tumors and one carcinosarcoma of the ovaries and screen hundreds of protein kinase compounds currently FDA-approved or in clinical development. In all cases we could identify drugs causing significant reduction in cell viability, number and size of organoids within a week from surgery, a timeline compatible with therapeutic decision making.
biorxiv cancer-biology 0-100-users 2017Chromatin accessibility dynamics of myogenesis at single cell resolution, bioRxiv, 2017-06-27
AbstractOver a million DNA regulatory elements have been cataloged in the human genome, but linking these elements to the genes that they regulate remains challenging. We introduce Cicero, a statistical method that connects regulatory elements to target genes using single cell chromatin accessibility data. We apply Cicero to investigate how thousands of dynamically accessible elements orchestrate gene regulation in differentiating myoblasts. Groups of co-accessible regulatory elements linked by Cicero meet criteria of “chromatin hubs”, in that they are physically proximal, interact with a common set of transcription factors, and undergo coordinated changes in histone marks that are predictive of gene expression. Pseudotemporal analysis revealed a subset of elements bound by MYOD in myoblasts that exhibit early opening, potentially serving as the initial sites of recruitment of chromatin remodeling and histone-modifying enzymes. The methodological framework described here constitutes a powerful new approach for elucidating the architecture, grammar and mechanisms of cis-regulation on a genome-wide basis.
biorxiv genomics 100-200-users 2017General sexual desire, but not desire for uncommitted sexual relationships, tracks changes in women’s hormonal status, bioRxiv, 2017-06-27
AbstractSeveral recent longitudinal studies have investigated the hormonal correlates of both young adult women’s general sexual desire and, more specifically, their desire for uncommitted sexual relationships. Findings across these studies have been mixed, potentially because each study tested only small samples of women (Ns = 43, 33, and 14). Here we report results from a much larger (N = 375) longitudinal study of hormonal correlates of young adult women’s general sexual desire and their desire for uncommitted sexual relationships. Our analyses suggest that within-woman changes in general sexual desire are negatively related to progesterone, but are not related to testosterone or cortisol. We observed some positive relationships for estradiol, but these were generally only significant for solitary sexual desire. By contrast with our results for general sexual desire, analyses showed no evidence that changes in women’s desire for uncommitted sexual relationships are related to their hormonal status. Together, these results suggest that changes in hormonal status contribute to changes in women’s general sexual desire, but do not influence women’s desire for uncommitted sexual relationships.
biorxiv animal-behavior-and-cognition 100-200-users 2017Evaluating Metagenome Assembly on a Simple Defined Community with Many Strain Variants, bioRxiv, 2017-06-26
AbstractWe evaluate the performance of three metagenome assemblers, IDBA, MetaSPAdes, and MEGAHIT, on short-read sequencing of a defined “mock” community containing 64 genomes (Shakya et al. (2013)). We update the reference metagenome for this mock community and detect several additional genomes in the read data set. We show that strain confusion results in significant loss in assembly of reference genomes that are otherwise completely present in the read data set. In agreement with previous studies, we find that MEGAHIT performs best computationally; we also show that MEGAHIT tends to recover larger portions of the strain variants than the other assemblers.
biorxiv bioinformatics 100-200-users 2017