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This Week in PNAS: Apr 18, 2017

In the early, online version of the Proceedings of the National Academy of Sciences, researchers from Stanford University and the University of Texas at Austin explore the consequences of activating KRAS mutations in lung adenocarcinoma. Using a combination of array-based gene expression profiling, mass spec-based lipid assessments, and proteomic analyses, the team compared mouse and human lung cancer samples with or without KRAS mutations. Results from the analyses suggest KRAS proteins produced from mutated forms of the gene can activate the ERK2 protein, promote lipogenesis, and lead to fatty acid synthase induction. On the other hand, inhibition of the latter process appears to stem the proliferation of KRAS-mutated cancer cells.

A Johns Hopkins team introduces a bisulfite sequencing method designed to distinguish between two barcoded DNA strands in the genome as a means of finding and tallying up rare mutations. The BiSeqS method takes advantage of bisulfite conversion features to tell one DNA strand from another, the authors say, and pairs this treatment with barcoding on the targeted regions and on samples. The approach "allows individual mutations to be assessed on both strands (duplex sequencing) in a reliable manner, without creation of libraries and with a relatively small number of sequencing reads," they write.

Finally, investigators in China and the US take a look at the relationship between two different forms of DNA modification in bacteria: adenine methylation and phosphorothioation, a modification that swaps out a DNA backbone oxygen for a sulfur molecule. Based on mass spec, sequencing, and other analyses of Escherichia coli and Salmonella enterica representatives, the authors saw signs of "shared consensus sequences for two seemingly unrelated DNA modification system" that appears to point to potential coevolution between the two bacterial genome modification systems.