Analytical validation of NeXT Personal®, an ultra-sensitive personalized circulating tumor DNA assay.

We describe the analytical validation of NeXT Personal, an ultra-sensitive, tumor-informed circulating tumor DNA (ctDNA) assay for detecting residual disease, monitoring therapy response, and detecting recurrence in patients diagnosed with solid tumor cancers. NeXT Personal uses whole genome sequencing of tumor and matched normal samples combined with advanced analytics to accurately identify up to ~1,800 somatic variants specific to the patient's tumor. A personalized panel is created, targeting these variants and then used to sequence cell-free DNA extracted from patient plasma samples for ultra-sensitive detection of ctDNA.

Analytic validation of NeXT Dx™, a comprehensive genomic profiling assay.

We describe the analytic validation of NeXT Dx, a comprehensive genomic profiling assay to aid therapy and clinical trial selection for patients diagnosed with solid tumor cancers. Proprietary methods were utilized to perform whole exome and whole transcriptome sequencing for detection of single nucleotide variants (SNVs), insertions/deletions (indels), copy number alterations (CNAs), and gene fusions, and determination of tumor mutation burden and microsatellite instability. Variant calling is enhanced by sequencing a patient-specific normal sample from, for example, a blood specimen.

How the virus outsmarts the host: function and structure of cytomegalovirus MHC-I-like molecules in the evasion of natural killer cell surveillance.

Natural killer (NK) cells provide an initial host immune response to infection by many viral pathogens. Consequently, the viruses have evolved mechanisms to attenuate the host response, leading to improved viral fitness. One mechanism employed by members of the β-herpesvirus family, which includes the cytomegaloviruses, is to modulate the expression of cell surface ligands recognized by NK cell activation molecules.

Structural basis for dimerization in DNA recognition by Gal4.

Gal4 is a Zn2Cys6 binuclear cluster containing transcription factor that binds DNA as a homodimer and can activate transcription by interacting with the mutant Gal11P protein. Although structures have been reported of the Gal4 dimerization domain and the binuclear cluster domain bound to DNA as a dimer, the structure of the "complete" Gal4 dimer bound to DNA has not previously been described. Here we report the structure of a complete Gal4 dimer bound to DNA and additional biochemical studies to address the molecular basis for Gal4 dimerization in DNA binding.