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This Week in PNAS: Jan 3, 2017

In the early, online edition of the Proceedings of the National Academy of Sciences, an international team led by investigators at the Broad Institute present findings from a population genomic study of hematopoietic regulation. By bringing together available blood cell trait data with genome sequences or SNP genotyping profiles for thousands of Estonian Biobank participants, the researchers narrowed in on 17 loci linked to 14 blood cell traits with genome-wide significance. They went on to incorporate clues from multiple fine-mapping methods and past epigenetic studies, including sequencing analyses of chromatin accessibility, chromatin interactions, and so on, to explore potential regulators of blood cell development and differentiation.

Researchers from the US and the UK use computational approaches to consider the potential impact between gene drive mosquito approaches and malaria control in sub-Saharan Africa. Through a series of mathematical modeling analyses representing various gene drive approaches, field settings, seasons, timing, and frequency of mosquito release, the team argues that all of the gene drive approaches analyzed have the potential to surpass existing strategies for malaria control and elimination. "Provided potential barriers to success are surmounted," the investigators write, "each achieves high efficacy at reducing transmission potential and lower delivery requirements in logistically challenged settings."

Finally, a Boston team takes a look at proteasome subunit patterns in thousands of tumor samples or cancer cell lines, with an eye to understanding and predicting the effectiveness of proteasome inhibitor treatments. Starting with gene expression data for nearly 800 cancer cell lines in the Genomics of Drugs Sensitivity in Cancer (GDSC) database, the researchers saw a dip in 19S proteasome subunit expression in a subset of cell lines. In the GDSC dataset and samples from the Cancer Cell Line Encyclopedia and the Cancer Genome Atlas project, they subsequently found that declines in expression of at least one 19S proteasome subunit was associated with proteasome inhibitor resistance and poor outcomes in individuals with multiple myeloma who were treated with the proteasome inhibitor bortezomib.