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This Week in PNAS: Jan 26, 2010

In the early, online edition of PNAS this week, Japanese and American researchers report on stripped down bacterial genomes developed from the industrial bug Streptomyces avermitilis. By systematically deleting non-essential genes, the team was left with deletion mutations containing between 81 and 83 percent of the original S. avermitilis genome. They then tested these mutants to see which, if any, were optimal hosts for producing foreign secondary metabolites such as streptomycin. "These findings highlight the strength and flexibility of engineered S. avermitilis as a model host for heterologous gene expression," they write, "resulting in the production of exogenous natural and unnatural metabolites."

A Baylor College of Medicine team describes their method for purifying and identifying endogenous protein complexes. After developing their high-throughput immunoprecipitation and mass spectrometry-based protocol, the researchers came up with specificity filters and constraints for data generated using the protocol — validating the approach by analyzing complexes of transcriptional co-regulators.

Johns Hopkins researchers examine the role of phosphatidylinositol-3-kinase signaling in human colorectal cancer. By inactivating three genes in this pathway in colon cancer cell lines, the team found evidence suggesting the PI3K signaling pathway is altered in this type of cancer. "These findings show that the PI3K signaling pathway is wired differently in human cancer cells than in other cell types or organisms," they write, "which has important implications for the design and testing of drugs that target this pathway."

And in a paper scheduled to appear online this week in PNAS, James Musser and his team report on their sequencing and comparison of nearly 100 M3 serotype group A Streptococcus genomes. The researchers used a short read approach to sequence 87 of the 344 isolates collected in Ontario during three epidemics over about 15 years as part of a prospective, population-based study, comparing these with eight other sequenced isolates. Based on their sequencing, genotyping, and transcriptome analyses, the team found characteristic patterns linked to specific epidemics and patient phenotypes. For more information, check out a related news story in our sister publication GenomeWeb Daily News.

The Scan

Expanded Genetic Testing Uncovers Hereditary Cancer Risk in Significant Subset of Cancer Patients

In Genome Medicine, researchers found pathogenic or likely pathogenic hereditary cancer risk variants in close to 17 percent of the 17,523 patients profiled with expanded germline genetic testing.

Mitochondrial Replacement Therapy Embryos Appear Largely Normal in Single-Cell 'Omics Analyses

Embryos produced with spindle transfer-based mitochondrial replacement had delayed demethylation, but typical aneuploidy and transcriptome features in a PLOS Biology study.

Cancer Patients Report Quality of Life Benefits for Immune Checkpoint Inhibitors

Immune checkpoint inhibitor immunotherapy was linked in JAMA Network Open to enhanced quality of life compared to other treatment types in cancer patients.

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.