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.