Bercovici, S. | bioRxiv Science

bioRxiv2018

Liquid biopsy for infectious diseases: Sequencing of cell-free plasma to detect pathogen DNA in patients with invasive fungal disease

Diagnosis of life-threatening deep-seated infections currently requires invasive sampling of the infected tissue to provide a microbiologic diagnosis. These procedures can lead to high morbidity in patients and add to healthcare costs. Here we describe a novel next-generation sequencing assay that was used to detect pathogen-derived cell-free DNA in peripheral blood of patients with biopsy-proven invasive fungal infections. The non-invasive nature of this approach could provide rapid, actionable treatment information for invasive fungal infections when a biopsy is not possible.

microbiology↗

bioRxiv2016

Large-scale Population Genotyping from Low-coverage Sequencing Data using a Reference Panel

In recent years, several large-scale whole-genome projects sequencing tens of thousands of individuals were completed, with larger studies are underway. These projects aim to provide high-quality genotypes for a large number of whole genomes in a cost-efficient manner, by sequencing each genome at low coverage and subsequently identifying alleles jointly in the entire cohort. Here we present Ref-Reveel, a novel method for large-scale population genotyping. We show that Ref-Reveel provides genotyping at a higher accuracy and higher efficiency in comparison to existing methods by applying our method to one of the largest whole-genome sequencing datasets presently available to the public. We further show that utilizing the resulting genotype panel as references, through the Ref-Reveel framework, greatly improves the ability to call genotypes accurately on newly sequenced genomes. In addition, we present a Ref-Reveel pipeline that is applicable for genotyping of very small datasets. In summary, Ref-Reveel is an accurate, scalable and applicable method for a wide range of genotyping scenarios, and will greatly improves the quality of calling genomic alterations in current and future large-scale sequencing projects.

bioinformatics↗