Curators' Favorite Papers

Concordance between Research Sequencing and Clinical Pharmacogenetic Genotyping in the eMERGE-PGx StudyAuthors: Rasmussen-Torvik LJ, Almoguera B, Doheny KF, Freimuth RR, Gordon AS, Hakonarson H, Hawkins JB, Husami A, Ivacic L, Kullo IJ, Linderman MD, Manolio TA, Obeng AO, Pellegrino R, Prows CA, Ritchie MD, Smith M, Stallings SC, Wolf WA, Zhang K, Scott SA.A new paper in “The Journal of Molecular Diagnostics” examines whether “orthogonal confirmation” of next generation sequencing (NGS) results is necessary. The authors examined data from subjects enrolled as part of the Electronic Medical Records and Genomics Pharmacogenomics (eMERGE-PGx) study. The authors found that for 4077 patients (and 67,900 variants) the per-sample concordance rate was 0.972, while the per-variant concordance rate was 0.997. Source of error for the NGS sequencing results were attributed to the accidental swapping of samples. The source of error in clinical genotyping was attributed to the presence of rare variants near primer annealing sites which may have disrupted hybridization and led to amplification of the other allele ("allele drop-out"). The authors conclude that high concordance between the two sequencing modalities obviates the need for orthogonal sequence confirmation in NGS samples and that concordance could be improved by implementing practices known to further reduce error. https://www.ncbi.nlm.nih.gov/pubmed/28502727Drugs in space: Pharmacokinetics and pharmacodynamics in astronautsAuthors: Johannes Kasta, Yichao Yua, Christoph N. Seubertb, Virginia E. Wotringc,d, Hartmut Derendorfa,A review in “The European Journal of Pharmaceutical Sciences” discusses factors that may affect drug pharmacokinetics and pharmacodynamics, as well as drug safety and efficacy in a very particular situation: space. In addition to the expected effects of microgravity on drug absorption, distribution, metabolism, and elimination (ADME), studies in space have also shown that drug stability, the immune system, and bacterial growth patterns are also affected by microgravity and all must be taken into consideration to ensure drug efficacy and safety during spaceflight. https://www.ncbi.nlm.nih.gov/pubmed/28533143