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"Albrecht, Benjamin"
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Cuneiform texts from various collections
This text features 217 cuneiform texts, found in small collections throughout the world, that date from the late third to the late first millennia BCE and includes inscriptions, letters, administrative documents, and literary works in Akkadian and Sumerian.
BOOK
MEGAN-LR: new algorithms allow accurate binning and easy interactive exploration of metagenomic long reads and contigs
Background
There are numerous computational tools for taxonomic or functional analysis of microbiome samples, optimized to run on hundreds of millions of short, high quality sequencing reads. Programs such as MEGAN allow the user to interactively navigate these large datasets. Long read sequencing technologies continue to improve and produce increasing numbers of longer reads (of varying lengths in the range of 10k-1M bps, say), but of low quality. There is an increasing interest in using long reads in microbiome sequencing, and there is a need to adapt short read tools to long read datasets.
Methods
We describe a new LCA-based algorithm for taxonomic binning, and an interval-tree based algorithm for functional binning, that are explicitly designed for long reads and assembled contigs. We provide a new interactive tool for investigating the alignment of long reads against reference sequences. For taxonomic and functional binning, we propose to use LAST to compare long reads against the NCBI-nr protein reference database so as to obtain frame-shift aware alignments, and then to process the results using our new methods.
Results
All presented methods are implemented in the open source edition of MEGAN, and we refer to this new extension as MEGAN-LR (MEGAN long read). We evaluate the LAST+MEGAN-LR approach in a simulation study, and on a number of mock community datasets consisting of Nanopore reads, PacBio reads and assembled PacBio reads. We also illustrate the practical application on a Nanopore dataset that we sequenced from an anammox bio-rector community.
Reviewers
This article was reviewed by Nicola Segata together with Moreno Zolfo, Pete James Lockhart and Serghei Mangul.
Conclusion
This work extends the applicability of the widely-used metagenomic analysis software MEGAN to long reads. Our study suggests that the presented LAST+MEGAN-LR pipeline is sufficiently fast and accurate.
Journal Article
A young adult with COVID-19 and multisystem inflammatory syndrome in children (MIS-C)-like illness: a case report
Background
A healthy 25-year-old woman developed COVID-19 disease with clinical characteristics resembling Multisystem Inflammatory Syndrome in Children (MIS-C), a rare form of COVID-19 described primarily in children under 21 years of age.
Case presentation
The patient presented with 1 week of weakness, dyspnea, and low-grade fevers, followed by mild cough, sore throat, vomiting, diarrhea, and lymph node swelling. She was otherwise healthy, with no prior medical history. Her hospital course was notable for profound acute kidney injury, leukocytosis, hypotension, and cardiac dysfunction requiring ICU admission and vasopressor support. MIS-C-like illness secondary to COVID-19 was suspected due to physical exam findings of conjunctivitis, mucositis, and shock. She improved following IVIG, aspirin, and supportive care, and was discharged on hospital day 5.
Conclusion
MIS-C-like illness should be considered in adults presenting with atypical clinical findings and concern for COVID-19. Further research is needed to support the role of IVIG and aspirin in this patient population.
Journal Article
MAIRA- real-time taxonomic and functional analysis of long reads on a laptop
Background
Advances in mobile sequencing devices and laptop performance make metagenomic sequencing and analysis in the field a technologically feasible prospect. However, metagenomic analysis pipelines are usually designed to run on servers and in the cloud.
Results
MAIRA is a new standalone program for interactive taxonomic and functional analysis of long read metagenomic sequencing data on a laptop, without requiring external resources. The program performs fast, online, genus-level analysis, and on-demand, detailed taxonomic and functional analysis. It uses two levels of frame-shift-aware alignment of DNA reads against protein reference sequences, and then performs detailed analysis using a protein synteny graph.
Conclusions
We envision this software being used by researchers in the field, when access to servers or cloud facilities is difficult, or by individuals that do not routinely access such facilities, such as medical researchers, crop scientists, or teachers.
Journal Article
Effect of UTI treatment guideline implementation on antibiotic duration and selection
Background: Clinicians have variable prescribing practices for treating urinary tract infections (UTI), resulting in broader and longer treatment durations than necessary. In March 2023, guidelines for UTI treatment were developed and disseminated across our hospital system. Methods: We evaluated inpatients at Emory University Hospital (EUH) who received antibiotics with an indication of UTI between November 2022 and March 2024 to investigate implementation effect on treatment duration and choice. We characterized days of therapy (DOT) by performing interrupted time series analysis, adjusting for demographic and clinical variables. Additionally, we looked at percent use of guideline concordant antibiotics chosen before and after implementation. Results: A total of 978 cases of UTIs were evaluated pre-guideline implementation among 621 (63.5%) females with 490 (50.1%) Black patients. A total of 1420 cases of UTIs were evaluated post-guideline implementation among 843 (59.4%) females with 693 (48.8%) Black patients. With inpatient UTI DOT, following implementation there was an increase by 31.5 DOT/month with a sustained increase by 6.25 DOT/month with no statistically significant change. Total UTI DOT (including outpatient) showed a sustained decrease by 21.1 DOT/month with no overall statistical significance. With inpatient UTI guideline concordance, following implementation there was an increase by 2.5% per month with a sustained increase by 0.7% per month with no statistically significant change. Total UTI guideline concordance (including outpatient) showed a sustained increase by 1.4% per month with no overall statistical significance. Conclusion: Guideline implementation for UTI treatment did not lead to statically significant change in DOT or guideline concordant prescribing at EUH.
Journal Article
Real-world evaluation of ceftriaxone-related safety events: a stewardship call to action
A ceftriaxone safety alert prompted a review of rapid response and cardiac arrest events in relation to the timing of intravenous cephalosporin administrations across a large health system. Despite high utilization, we found a low rate of significant ceftriaxone-related adverse events with a similar incidence as other intravenous cephalosporins.
Journal Article
Computing all hybridization networks for multiple binary phylogenetic input trees
Background
The computation of phylogenetic trees on the same set of species that are based on different orthologous genes can lead to incongruent trees. One possible explanation for this behavior are interspecific hybridization events recombining genes of different species. An important approach to analyze such events is the computation of hybridization networks.
Results
This work presents the first algorithm computing the hybridization number as well as a set of representative hybridization networks for multiple binary phylogenetic input trees on the same set of taxa. To improve its practical runtime, we show how this algorithm can be parallelized. Moreover, we demonstrate the efficiency of the software Hybroscale, containing an implementation of our algorithm, by comparing it to PIRNv2.0, which is so far the best available software computing the exact hybridization number for multiple binary phylogenetic trees on the same set of taxa. The algorithm is part of the software Hybroscale, which was developed specifically for the investigation of hybridization networks including their computation and visualization. Hybroscale is freely available
1
and runs on all three major operating systems.
Conclusion
Our simulation study indicates that our approach is on average 100 times faster than PIRNv2.0. Moreover, we show how Hybroscale improves the interpretation of the reported hybridization networks by adding certain features to its graphical representation.
Journal Article
Pursuing Experimental Reproducibility: An Efficient Protocol for the Preparation of Cerebrospinal Fluid Samples for NMR-Based Metabolomics and Analysis of Sample Degradation
NMR-based metabolomics investigations of human biofluids offer great potential to uncover new biomarkers. In contrast to protocols for sample collection and biobanking, procedures for sample preparation prior to NMR measurements are still heterogeneous, thus compromising the comparability of the resulting data. Herein, we present results of an investigation of the handling of cerebrospinal fluid (CSF) samples for NMR metabolomics research. Origins of commonly observed problems when conducting NMR experiments on this type of sample are addressed, and suitable experimental conditions in terms of sample preparation and pH control are discussed. Sample stability was assessed by monitoring the degradation of CSF samples by NMR, hereby identifying metabolite candidates, which are potentially affected by sample storage. A protocol was devised yielding consistent spectroscopic data as well as achieving overall sample stability for robust analysis. We present easy to adopt standard operating procedures with the aim to establish a shared sample handling strategy that facilitates and promotes inter-laboratory comparison, and the analysis of sample degradation provides new insights into sample stability.
Journal Article
Reductions in inpatient fluoroquinolone use and postdischarge Clostridioides difficile infection (CDI) from a systemwide antimicrobial stewardship intervention
Objective:To determine the impact of an inpatient stewardship intervention targeting fluoroquinolone use on inpatient and postdischarge Clostridioides difficile infection (CDI).Design:We used an interrupted time series study design to evaluate the rate of hospital-onset CDI (HO-CDI), postdischarge CDI (PD-CDI) within 12 weeks, and inpatient fluoroquinolone use from 2 years prior to 1 year after a stewardship intervention.Setting:An academic healthcare system with 4 hospitals.Patients:All inpatients hospitalized between January 2017 and September 2020, excluding those discharged from locations caring for oncology, bone marrow transplant, or solid-organ transplant patients.Intervention:Introduction of electronic order sets designed to reduce inpatient fluoroquinolone prescribing.Results:Among 163,117 admissions, there were 683 cases of HO-CDI and 1,104 cases of PD-CDI. In the context of a 2% month-to-month decline starting in the preintervention period (P < .01), we observed a reduction in fluoroquinolone days of therapy per 1,000 patient days of 21% after the intervention (level change, P < .05). HO-CDI rates were stable throughout the study period. In contrast, we also detected a change in the trend of PD-CDI rates from a stable monthly rate in the preintervention period to a monthly decrease of 2.5% in the postintervention period (P < .01).Conclusions:Our systemwide intervention reduced inpatient fluoroquinolone use immediately, but not HO-CDI. However, a downward trend in PD-CDI occurred. Relying on outcome measures limited to the inpatient setting may not reflect the full impact of inpatient stewardship efforts.
Journal Article
