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This Week in Cell: Dec 17, 2014

American and Israeli researchers report on findings from a chemical genetic screen that they used to systematically knock down genes in Cryptococcus neoformans, a fungal species known for causing difficult to treat infections that contribute to mortality risk in individuals with HIV/AIDS. The team treated nearly 1,500 C. neoformans gene deletion strains with more than 400 small molecules to track chemical responses in the knockouts. That information was then used to try to predict and test new targets for C. neoformans antifungal agents. "Our work establishes a chemical-genetic foundation for approaching an infection responsible for greater than one-third of AIDS-related deaths," the study's authors write.

A team from the US and Canada introduces an algorithm for incorporating findings from RNA interference screens with other genomic data. For their proof-of-principle study, researchers applied this computational approach, called Helios, to look for breast cancer driver events involving somatic copy number alterations. Using genomic data generated by The Cancer Genome Atlas for almost 800 breast cancer tumors, together with information on 27 breast cancer cell lines assessed using genome-wide RNAi screening and other methods, the team tracked down dozens of potential driver regions involving DNA amplifications — sites that affected known breast cancer contributors as well as new candidate driver genes tested in vitro.

Using a method known as in situ Hi-C that combines restriction enzyme digestion with nuclear ligation, researchers from Baylor College of Medicine, the Broad Institute, and elsewhere mapped the three-dimensional chromatin contact patterns in nine haploid or diploid cell lines originating from human or mouse tissues at roughly one kilobase resolution. The work revealed more than 10,000 chromatin loops, as well as partitioning within the genome that involved contact domains with different histone modification and sub-compartmentalization patterns.

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