Two studies by VHFC researchers were published in the August 8 edition of the journal Cell. One study, led by Erica Saphire, defines antibody residues that allow potent and broad neutralizing activity of Lassa virus in a set of three neutralizing antibodies. Combined with findings from analyses of inferred germline precursors the researchers increased the neutralization potency and breadth of these antibodies to include all major Lassa virus lineages, which is critical to develop potent therapeutics and for vaccine design and assessment.
In the second study, Pardis Sabeti and colleagues provides the most comprehensive benchmarking to date, of metagenomic tools for taxonomic classification and pathogen identification.
Both papers can be read in the Journal Cell.
Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization.
Hastie KM, Cross RW, Harkins SS, Zandonatti MA, Koval AP, Heinrich ML, Rowland MM, Robinson JE, Geisbert TW, Garry RF, Branco LM, Saphire EO.
Cell. 2019 Aug 8;178(4):1004-1015.e14. doi: 10.1016/j.cell.2019.07.020.
Lassa virus (LASV) causes hemorrhagic fever and is endemic in West Africa. Protective antibody responses primarily target the LASV surface glycoprotein (GPC), and GPC-B competition group antibodies often show potent neutralizing activity in humans. However, which features confer potent and broadly neutralizing antibody responses is unclear. Here, we compared three crystal structures of LASV GPC complexed with GPC-B antibodies of varying neutralization potency. Each GPC-B antibody recognized an overlapping epitope involved in binding of two adjacent GPC monomers and preserved the prefusion trimeric conformation. Differences among GPC-antibody interactions highlighted specific residues that enhance neutralization. Using structure-guided amino acid substitutions, we increased the neutralization potency and breadth of these antibodies to include all major LASV lineages. The ability to define antibody residues that allow potent and broad neutralizing activity, together with findings from analyses of inferred germline precursors, is critical to develop potent therapeutics and for vaccine design and assessment.
Benchmarking Metagenomics Tools for Taxonomic Classification.
Ye SH, Siddle KJ, Park DJ, Sabeti PC.
Cell. 2019 Aug 8;178(4):779-794. doi: 10.1016/j.cell.2019.07.010
Metagenomic sequencing is revolutionizing the detection and characterization of microbial species, and a wide variety of software tools are available to perform taxonomic classification of these data. The fast pace of development of these tools and the complexity of metagenomic data make it important that researchers are able to benchmark their performance. Here, we review current approaches for metagenomic analysis and evaluate the performance of 20 metagenomic classifiers using simulated and experimental datasets. We describe the key metrics used to assess performance, offer a framework for the comparison of additional classifiers, and discuss the future of metagenomic data analysis.