Ang, M. Y. | bioRxiv Science

bioRxiv2024

hAMRonization: Enhancing antimicrobial resistance prediction using the PHA4GE AMR detection specification and tooling

The detection of antimicrobial resistance (AMR) markers directly from genomic or metagenomic data is becoming a standard clinical and public health procedure. This has resulted in the development of a number of different bioinformatic AMR prediction tools. Although many may implement similar principles, these tools differ significantly in their supported inputs, search algorithms, parameterisation, and underlying reference databases. Each of these tools generates a report of detected AMR genes or variants in a distinct, non-standard, format. This presents a huge barrier to the comparison of results and to the modularity of tools for AMR gene prediction within bioinformatic workflows. In collaboration with 17 public health laboratories across 10 countries, the Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) data structures working group has developed and piloted a standardized output specification for the bioinformatic detection of AMR from microbial genomes. In this report, we discuss hAMRonization, a python package and command-line utility, which implements PHA4GEs AMR specification to combine the outputs of disparate antimicrobial resistance gene detection tools into a single unified format. hAMRonization can be easily extended and currently supports 18 different tools (both species-agnostic and species-specific) for the detection of genes and/or variants conferring AMR. The harmonized reports are available in tabular form, JSON format or through an interactive HTML file (e.g., https://maguire-lab.github.io/assets/interactive_report_demo.html) that can be opened within the browser for navigable data exploration. As of 2024-03-07 hAMRonization has been downloaded [~]12,500 times, incorporated into >9 public bioinformatic tools and workflows, and been internally adopted by several national and international public health groups. The hAMRonization tool and underlying specification are open-source and freely available through PyPI, conda and GitHub (https://github.com/pha4ge/hAMRonization).

bioinformatics↗

bioRxiv2022

Single-nucleus ATAC-seq elucidates major modules of gene regulation in the development of non-alcoholic fatty liver disease

We investigated the progression of non-alcoholic fatty liver disease (NAFLD) from fatty liver to steatohepatitis using single-nucleus and bulk ATAC-seq on the livers of rats fed a high-fat diet (HFD). Rats fed HFD for 4 weeks developed fatty liver, and those fed HFD for 8 weeks further progressed to steatohepatitis. We observed an increase in the proportion of inflammatory macrophages, consistent with the pathological progression. Utilizing machine learning, we divided global gene regulation into modules, wherein transcription factors within a module could regulate genes within the same module, reaffirming known regulatory relationships between transcription factors and biological processes. We identified core genes--central to co-expression and protein-protein interaction--for the biological processes discovered. Notably, a large part of the core genes overlapped with genes previously implicated in NAFLD. Single-nucleus ATAC-seq, combined with data-driven statistical analysis, offers insight into in vivo global gene regulation as a combination of modules and assists in identifying core genes of relevant biological processes. Summary blurbThis study uncovers cell type-specific global gene regulation in NAFLD progression, identifying core genes and shedding light on the diseases molecular mechanisms.

genomics↗