Alsray1628

Antimicrobial use (AU) in days of therapy per 1000 patient-days (DOT/1000pd) varies widely among children's hospitals. We evaluated indirect standardization to adjust AU for case mix, a source of variation inadequately addressed by current measurements. Hospitalizations from the Pediatric Health Information System were grouped into 85 clinical strata. Observed to expected (OE) ratios were calculated by indirect standardization and compared to DOT/1000pd. Outliers were defined by OE z-scores. Antibacterial DOT/1000pd ranged from 345 to 776 (2.2-fold variation; interquartile range [IQR] 552-679), whereas OE ratios ranged from 0.8 to 1.14 (1.4-fold variation; IQR 0.93-1.05). OE ratios were moderately correlated with DOT/1000pd (correlation estimate 0.44; 95% CI 0.19-0.64; p=0.0009). Using indirect standardization to adjust for case mix reduces apparent AU variation and may enhance stewardship efforts by providing adjusted comparisons to inform interventions.Molluscs biomineralize structures that vary in composition, form, and function, prompting questions about the genetic mechanisms responsible for their production and the evolution of these mechanisms. Chitons (Mollusca, Polyplacophora) are a promising system for studies of biomineralization because they build a range of calcified structures including shell plates and spine- or scale-like sclerites. Chitons also harden the calcified teeth of their rasp-like radula with a coat of iron (as magnetite). Here we present the genome of the West Indian fuzzy chiton Acanthopleura granulata, the first from any aculiferan mollusc. The A. granulata genome contains homologs of many genes associated with biomineralization in conchiferan molluscs. We expected chitons to lack genes previously identified from pathways conchiferans use to make biominerals like calcite and nacre because chitons do not use these materials in their shells. Surprisingly, the A. granulata genome has homologs of many of these genes, suggesting that the ancestral mollusc may have had a more diverse biomineralization toolkit than expected. The A. granulata genome has features that may be specialized for iron biomineralization, including a higher proportion of genes regulated directly by iron than other molluscs. A. granulata also produces two isoforms of soma-like ferritin one is regulated by iron and similar in sequence to the soma-like ferritins of other molluscs, and the other is constitutively translated and is not found in other molluscs. The A. granulata genome is a resource for future studies of molluscan evolution and biomineralization.

Improvements in DNA sequencing technology and computational methods have led to a substantial increase in the creation of high-quality genome assemblies of many species. To understand the biology of these genomes, annotation of gene features and other functional elements is essential; however for most species, only the reference genome is well-annotated.

One strategy to annotate new or improved genome assemblies is to map or 'lift over' the genes from a previously-annotated reference genome. Here we describe Liftoff, a new genome annotation lift-over tool capable of mapping genes between two assemblies of the same or closely-related species. Liftoff aligns genes from a reference genome to a target genome and finds the mapping that maximizes sequence identity while preserving the structure of each exon, transcript, and gene. We show that Liftoff can accurately map 99.9% of genes between two versions of the human reference genome with an average sequence identity >99.9%. see more We also show that Liftoff can map genes across species by successfully lifting over 98.3% of human protein-coding genes to a chimpanzee genome assembly with 98.2% sequence identity.

Liftoff can be installed via bioconda and PyPI. Additionally, the source code for Liftoff is available at https//github.com/agshumate/Liftoff.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.

MicroRNAs (miRNAs) are short (∼24nt), non-coding RNAs, which downregulate gene expression in many species and physiological processes. Many details regarding the mechanism which governs miRNA-mediated repression continue to elude researchers.

We elucidate the interplay between the coding sequence and the 3'UTR, by using elastic net regularization and incorporating translation-related features to predict miRNA-mediated repression. We find that miRNA binding sites at the end of the coding sequence contribute to repression, and that weak binding sites are linked to effective de-repression, possibly as a result of competing with stronger binding sites. Furthermore, we propose a recycling model for miRNAs dissociated from the open reading frame (ORF) by traversing ribosomes, explaining the observed link between increased ribosome density/traversal speed and increased repression. We uncover a novel layer of interaction between the coding sequence and the 3'UTR (untranslated region) and suggest the ORF has a larger role than previously thought in the mechanism of miRNA-mediated repression.

The code is freely available at https//github.com/aescrdni/miRNA_model.

Supplementary data are available at Bioinformatics online.

Supplementary data are available at Bioinformatics online.Increasing evidence supports the notion that different regions of a genome have unique rates of molecular change. This variation is particularly evident in bacterial genomes where previous studies have reported gene expression and essentiality tend to decrease, whereas substitution rates usually increase with increasing distance from the origin of replication. Genomic reorganization such as rearrangements occur frequently in bacteria and allow for the introduction and restructuring of genetic content, creating gradients of molecular traits along genomes. Here, we explore the interplay of these phenomena by mapping substitutions to the genomes of Escherichia coli, Bacillus subtilis, Streptomyces, and Sinorhizobium meliloti, quantifying how many substitutions have occurred at each position in the genome. Preceding work indicates that substitution rate significantly increases with distance from the origin. Using a larger sample size and accounting for genome rearrangements through ancestral reconstruction, our analysis demonstrates that the correlation between the number of substitutions and the distance from the origin of replication is significant but small and inconsistent in direction.