OptiDiff: structural variation detection from single optical mapping reads

Detecting structural variation (SV) in eukaryotic genomes is of broad interest due to its often dramatic phenotypic effects, but remains a major, costly challenge based on DNA sequencing data. A cost-effective alternative in detecting large-scale SV has become available with advances in optical mapping technology. However, the algorithmic approaches to identifying SVs from optical mapping data are limited. Here, we propose a novel, open-source SV detection tool, OptiDiff, which employs a single molecule based approach to detect and classify homozygous and heterozygous SVs at coverages as low as 20x, showing better performance than the state of the art.

Patterns of Structural Variation Define Prostate Cancer Across Disease States

The complex genomic landscape of prostate cancer evolves across disease states under therapeutic pressure directed toward inhibiting androgen receptor (AR) signaling. While significantly altered genes in prostate cancer have been extensively defined, there have been fewer systematic analyses of how structural variation reflects the genomic landscape of this disease. We comprehensively characterized structural alterations across 278 localized and 143 metastatic prostate cancers profiled by whole genome and transcriptome sequencing. We observed distinct significantly recurrent breakpoints in localized and metastatic castration-resistant prostate cancers (mCRPC), with pervasive alterations in noncoding regions flanking the AR, MYC, FOXA1, and LSAMP genes in mCRPC. We defined nine subclasses of mCRPC based on signatures of structural variation, each associated with distinct genetic features and clinical outcomes. Our results comprehensively define patterns of structural variation in prostate cancer and identify clinically actionable subgroups based on whole genome profiling.

Structural variation of the 3-acetamido-4,5,6-trihydroxyazepane iminosugar through epimerization and C- alkylation leads to low micromolar HexAB and NagZ inhibitors

We report the synthesis of seven-membered iminosugars derived from a 3S-acetamido-4R,5R,6S-trihydroxyazepane scaffold and their evaluation as inhibitors of functionally related exo-N-acetylhexosaminidases including human O-GlcNAcase (OGA), human lysosomal b-hexosaminidase (HexAB), and...

IDENTIFYING PLANT GENES SHAPING MICROBIOTA COMPOSITION IN THE BARLEY RHIZOSPHERE

A prerequisite to exploiting soil microbes for sustainable crop production is the identification of the plant genes shaping microbiota composition in the rhizosphere, the interface between roots and soil. Here we used metagenomics information as an external quantitative phenotype to map the host genetic determinants of the rhizosphere microbiota in wild and domesticated genotypes of barley, the fourth most cultivated cereal globally. We identified a small number of loci with a major effect on the composition of rhizosphere communities. One of those, designated the QRMC-3HS locus, emerged as a major determinant of microbiota composition. We then subjected soil-grown sibling lines harbouring contrasting alleles at QRMC-3HS and hosting contrasting microbiotas to comparative root RNA-seq profiling. This allowed us to identify three primary candidate genes, including a Nucleotide-Binding-Leucine-Rich-Repeat (NLR) gene in a region of structural variation of the barley genome. Our results provide novel insights into the footprint of crop improvement on the plants capacity of shaping rhizosphere microbes.

Differences of the stem vascular system across populations of two tropical species under contrasting water conditions

Structural differences in the secondary vascular tissues among habitats can contribute to understanding species performances, especially regarding water and photosynthate transport. The pattern of association between the secondary xylem tissue and water availability from the environment has been widely studied, unlike the secondary phloem, which has been barely explored. Here, we evaluated the structural variation of the secondary xylem and phloem in stems of four populations of two tropical tree species under contrasting water conditions. We also investigated the mirrored structure between both tissues. At dry sites, Moquiniastrum polymorphum had higher vessel density, thicker xylem fibers cell walls, and taller rays in both tissues commonly associated with safe transport, in agreement with our expectations. In contrast, the populations of Zanthoxylum rhoifolium had most features in disagreement with the water availability of each site. The perforation and sieve plates, the ray composition, and the axial parenchyma were similar in the two tree species’ xylem and phloem tissues. However, the quantitative descriptors of cell sizes were not correlated between the xylem and phloem. In general, there is a different pattern of morphological variation across sites in the two tropical tree species, highlighting that any generalization regarding the vascular system structure across environments should be avoided. Xylem and phloem revealed a mirrored structure in a few qualitative features, not followed by the dimensions of different cell types. Future research needs to explore the causes of the unexpected structural variation in the vascular system across populations in tropical tree species.