Orthogonal Comparison of Four Plasma NGS Tests With Tumor Suggests Technical Factors are a Major Source of Assay Discordance.

Purpose: Discordance between plasma and tumor variant calling has been attributed primarily to tumor heterogeneity, whereas technical variables remain largely unexplored.

Materials And Methods: To measure these variables, we tested four next-generation sequencing (NGS) gene panel assays for mutations in circulating tumor DNA (ctDNA) using replicate sets of 24 plasma samples and compared the results with matched tumor-normal tissue pairs.

Results: Our orthogonal approach identified false-negative (FN) and false-positive (FP) variants with high confidence and revealed substantial variability among the ctDNA assays, with a range of sensitivity (38% to 89%) and positive predictive value (36% to 80%).

Prioritisation of structural variant calls in cancer genomes.

Sensitivity of short read DNA-sequencing for gene fusion detection is improving, but is hampered by the significant amount of noise composed of uninteresting or false positive hits in the data. In this paper we describe a tiered prioritisation approach to extract high impact gene fusion events from existing structural variant calls. Using cell line and patient DNA sequence data we improve the annotation and interpretation of structural variant calls to best highlight likely cancer driving fusions.

Disambiguate: An open-source application for disambiguating two species in next generation sequencing data from grafted samples.

Grafting of cell lines and primary tumours is a crucial step in the drug development process between cell line studies and clinical trials. is a program for computationally separating the sequencing reads of two species derived from grafted samples. operates on DNA or RNA-seq alignments to the two species and separates the components at very high sensitivity and specificity as illustrated in artificially mixed human-mouse samples.

Defining actionable mutations for oncology therapeutic development.

Genomic profiling of tumours in patients in clinical trials enables rapid testing of multiple hypotheses to confirm which genomic events determine likely responder groups for targeted agents. A key challenge of this new capability is defining which specific genomic events should be classified as 'actionable' (that is, potentially responsive to a targeted therapy), especially when looking for early indications of patient subgroups likely to be responsive to new drugs. This Opinion article discusses some of the different approaches being taken in early clinical development to define actionable mutations, and describes our strategy to address this challenge in early-stage exploratory clinical trials.

Ecotype diversity and conversion in Photobacterium profundum strains.

Photobacterium profundum is a cosmopolitan marine bacterium capable of growth at low temperature and high hydrostatic pressure. Multiple strains of P. profundum have been isolated from different depths of the ocean and display remarkable differences in their physiological responses to pressure.

Genome sequence of the marine photoheterotrophic bacterium Erythrobacter sp. strain NAP1.

Here we report the full genome sequence of marine phototrophic bacterium Erythrobacter sp. strain NAP1. The 3.