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This Week in PNAS: Dec 12, 2017

In the early, online edition of the Proceedings of the National Academy of Sciences, researchers from the US and Canada explore the potential impacts that human genetic variation may have on CRISPR-Cas9 gene editing. Focusing on nearly two dozen potential therapeutic targets in the human genome and seven viral genome targets, the team analyzed genome sequences for more than 7,400 individuals, looking at consequences that genetic variants may have on on-target and off-target specificity for thousands of guide RNAs. On rare occasions, SNPs or small insertions and deletions "can reduce on-target CRISPR activity and increase off-target potential when targeting therapeutically implicated loci," the authors note, adding that "differential allele frequencies among populations may result in population-specific alterations in CRISPR targeting specificity." GenomeWeb has more on this, here.

A team from the University of Pittsburgh, James Madison University, and elsewhere present SEA-PHAGES ("Science Education Alliance-Phage Hunters Advancing Genomics and Evolutionary Science") — an inclusive research education community (iREC) framework and support system for undergraduate students participating in phage finding research. The SEA-PHAGES has reached more than 4,000 students at 104 institutions in its nine years of development, the researchers note. The research course spans phage isolation and sequencing, genome annotation, and comparative genomics, the authors explain, teaching concepts such as viral diversity and evolution. The authors note that "the iREC concept could have a transformative impact on science education when expanded to include additional research topics." 

Finally, researchers at Harvard Medical School and the Dana-Farber Cancer Institute search for gene expression profiles that mark breast cancer, using DNA sequence, copy number profiles, and RNA sequence data generated for the Cancer Genome Atlas project's breast cancer set as of early 2015. The team took an unbiased computational approach to finding transcriptional programs in breast tumors, including those coinciding with the presence of known cancer driver mutations. While their analyses did uncover examples of pronounced expression shifts in tumors with specific genetic changes, the authors note that "two other factors, proliferation rate and tumor lineage, are more dominant factors in shaping tumor transcriptional programs than genetic alterations."