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This Week in Genome Biology: Apr 1, 2009

A minireview by EBI's Paul Flicek checks in on Bowtie, a short-read aligner that's ultrafast and can align more than 25 million human genome reads per CPU hour with a memory footprint of approximately 1.3 gigabytes. Because DNA sequence data are coming in at record amounts, the "Bowtie sequence-alignment algorithm uses advanced data structures to help data analysis keep pace with data generation," Flicek writes in the abstract.

In this paper, scientists made the first computational model of the budding yeast ubiquitin system to look at the entire system as a whole, especially the function and interaction of various parts. Among other things, they found there to be functional diversification of SUMO-dependent Ub-ligases and identified novel components of SCF (Skp1-cullin-F-box) -dependent complexes, receptors in the ERAD (endoplasmic reticulum associated degradation) system, and a key role for Sus1 in chromatin dynamics. They also show a "major impact of the Ub-system on large parts of the proteome via its interaction with the transcription regulatory network."

Work led by Scripps' Kelly Frazer and Olivier Harismendy and JCVI's Samuel Levy evaluated the current next-gen sequencing platforms for their performance in targeted sequencing for sequence-based association studies. They found that all three platforms have high sensitivity in generating greater than 95 percent of base calls when compared to Sanger results, and that at higher coverage depth, base calling errors are both systematic and depend on local sequence characteristics.

In collaboration with researchers at LBNL, scientists have mapped sub-networks in the EGFR-MAPK pathway in 30 different breast cancer cell lines, showing that PAK1 may be a marker for sensitivity to MEK inhibitors. Mapping genomic, transcriptional, and proteomic data onto a model of EGFR-MEK signaling comprised of 539 molecular states and 396 active state signaling rules, they were able to come up with a functional test for breast cancer cells lines against three MEK inhibitors. They found that cell lines overexpressing PAK1 are "significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels."