Skip to main content
Premium Trial:

Request an Annual Quote

This Week in PNAS: Oct 4, 2016

In the early, online edition of the Proceedings of the National Academy of Sciences, researchers from the University of North Carolina at Chapel Hill introduce sequencing strategies to characterize the single-base DNA damage and nucleotide excision-based DNA repair patterns associated with cisplatin chemotherapy. As they demonstrated in the human lymphocyte cell line GM12878, the Damage-seq method takes advantage of DNA adducts formed in response to cisplatin-induced damage, using them to block replication by high-fidelity polymerase enzymes. On the other hand, excision repair sequencing, or XR-seq, tracks post-cisplatin repair by capturing and sequencing oligomers that get released during nucleotide excision repair.

Stanford University researchers Euan Ashley, Stephen Quake, and colleagues describe a case of long-QT syndrome caused by somatic mosaicism involving a mutation that occurred not long after fertilization. Using whole-genome sequencing, the team searched for suspicious mutations in an infant of Asian ancestry who developed a dangerous arrhythmia. The rapid sequencing strategy uncovered a variant in the SCN5A sodium channel gene, prompting follow-up trio exome sequencing, genotyping, and RNA sequencing on her cardiac tissue. The investigators found further evidence that the mosaic SCN5A mutation, found in just 8 percent or so of her cells, was contributing to the arrhythmia. They detected a handful of other cases with somatic mosaic mutations related to long-QT syndrome when they screened 7,500 more individuals with undiagnosed arrhythmia.

German researchers present a sequencing method designed to characterize transcripts depending on their interactions. The "gradient profiling by sequencing," or Grad-seq, combines sequencing with RNA and protein sedimentation in a glycerol gradient to group coding and non-coding transcripts based on RNA-protein interaction networks, the team says. In its proof-of-principle experiments, Grad-seq uncovered structured small RNAs interacting with a conserved protein called ProQ in pathogenic Salmonella enterica bacteria. "Given its generic ability to chart a functional RNA landscape irrespective of transcript length and sequence diversity, Grad-seq promises to define functional RNA classes and major RNA-binding proteins in both model species and genetically intractable organisms," the authors write.