Biology subjects

Edgar, R.

Publications and source records attributed to Edgar, R..

4 recordsLinked to original sources

bioRxiv2026

First community challenge for automated virus taxonomy

The rapid rate of virus discovery renders manual curation by taxonomy experts increasingly impractical, creating a need for reliable software that can reproducibly assign viral contigs to taxa at all fifteen ranks of the virus taxonomy. We led an open community challenge for the computational taxonomic classification of viruses and assembled a dataset of virus sequences combining expert-curated and metagenomic sequences. Seventeen teams contributed a total of thirty-four automated, fully reproducible classification pipelines. Most tools correctly assigned viruses belonging to established species, genera, or families, but viruses that are unclassified at those lower ranks remain challenging. This study provides datasets, open-source software, novel approaches, and recommendations to benchmark computational taxonomic classification of viruses, and support organizing the many viruses discovered in big omics data.

microbiology↗

bioRxiv2025

Discovery and Validation of Alternatives to VSV-G for Pseudotyping of Lentiviral Vectors for In Vivo Delivery of Anti-Tumor Transgenes

Though cell therapy for cancer is now widely used commercially and has been efficacious for tens of thousands of patients, conventional manufacturing methods are expensive and difficult to scale. An alternative approach is to deliver the relevant anti-tumor transgenes to T cells in vivo in the patient. Such "in vivo cell therapy" methods promise to be more scalable, with reduced cost of goods, since the same drug product can be administered to any patient. Typically, conventional cell therapy introduces anti-tumor transgenes into T cells using a lentivector pseudotyped with VSV-G. However, VSV-G is not cell type specific because its molecular target is present on a diversity of human cells, which may result in less than optimal pharmacology in vivo. Natures existing viral diversity presents the opportunity to identify alternative pseudotypes that are more optimal for in vivo cell therapy. In this study, we first performed a large-scale bioinformatic sequence search for G-proteins similar to VSV-G. We identified 166 G-proteins in the sequence search and then tested 9 in vitro for efficiency, specificity, and sensitivity of transgene delivery to various human immune cell phenotypes. We used the results from this screen to select three G-protein candidates for a pilot GFP transgene delivery study in humanized mice, using anti-CD3 antibody fragments for T cell tropism. One candidate G-protein performed significantly better than VSV-G, so we moved that candidate into tumor control studies in a humanized mouse model. This candidate G-protein was able to deliver an anti-tumor transgene to T cells, which subsequently cleared 100% of tumor burden in 100% of mice. We conclude that systematic screens for optimal lentivector designs can be used to identify optimized candidates for in vivo cell therapy.

cancer biology↗

bioRxiv2020

Genome analysis of Salmonella enterica serovar Typhimurium bacteriophage L, indicator for StySA (StyLT2III) restriction-modification system action

Bacteriophage L, a P22-like phage of Salmonella enterica sv Typhimurium LT2, was important for definition of mosaic organization of the lambdoid phage family and for characterization of restriction-modification systems of Salmonella. We report the complete genome sequences of bacteriophage L cI-40 13-am43 and L cII-101; the deduced sequence of wildtype L is 40,633 bp long with a 47.5% GC content. We compare this sequence with those of P22 and ST64T, and predict 71 Coding Sequences, 2 tRNA genes and 14 intergenic rho-independent transcription terminators. The overall genome organization of L agrees with earlier genetic and physical evidence; for example, no secondary immunity region (ImmI: ant, arc) or genes for superinfection exclusion (sieA and sieB) are present. Proteomic analysis confirmed identification of virion proteins, along with low levels of assembly intermediates and host cell envelope proteins. The genome of L is 99.9% identical at the nucleotide level to that reported for phage ST64T, despite isolation on different continents ~35 years apart. DNA modification by the epigenetic regulator Dam is generally incomplete. Dam modification is also selectively missing in one location, corresponding to the P22 phase-variation-sensitive promoter region of the serotype-converting gtrABC operon. The number of sites for SenLTIII (StySA) action may account for stronger restriction of L (13 sites) than of P22 (3 sites).

genetics↗

bioRxiv2018

UNCROSS2: identification of cross-talk in 16S rRNA OTU tables

Next-generation amplicon sequencing is widely used for surveying biological diversity in applications such as microbial metagenomics, immune system repertoire analysis and targeted tumor sequencing of cancer-associated genes. In such studies, assignment of reads to incorrect samples (cross-talk) is a well-documented problem that is rarely considered in practice. Here, I describe UNCROSS2, an algorithm designed to detect and filter cross-talk in OTU tables generated by next-generation sequencing of the 16S ribosomal RNA gene. On eight published datasets, cross-talk rates are estimated to range from 0.4% to 1.5% mis-assigned reads. On a mock community test, UNCROSS2 identifies spurious counts due to cross-talk with sensitivity [~]80% to 90% and error rate from [~]1% to [~]20%, but it is not clear whether the accuracy of the algorithm is sufficient to decisively improve diversity rates in practice.

bioinformatics↗