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This Week in PLoS: May 2, 2011

Investigators at the University of Miami Miller School of Medicine and at Life Technologies report in a PLoS One paper their "comparison of three targeted enrichment strategies on the SOLiD sequencing platform." They assessed the performance of Nimblegen's oligonucleotide hybridization array-based capture, Agilent's SureSelect oligonucleotide hybridization solution-based capture, and Raindance Technologies' multiplexed PCR-based approach. By analyzing the SOLiD sequencing results they generated for consistency of coverage depth across samples, on- versus off-target efficiency, allelic bias, and genotype concordance, the team found that the Raindance approach "demonstrated the highest versatility in assay design," although like Nimblegen's SeqCap, it "suffered from lower on-target efficiency in our experiments." Agilent's SureSelect, the team says, "exhibited superior on-target efficiency and correlation of read depths across samples."

The University of California, San Diego's Philip Bourne and his colleagues discuss in a recent PLoS Computational Biology paper using chemical systems biology for drug discovery efforts. In particular, Bourne et al. describe their use of a "structural proteome-wide off-target pipeline," with which they identified putative human off-targets of the HIV-protease inhibitor Nelfinavir. Among other things, the team says that its analysis uncovered a "molecular basis to explain the broad-spectrum anti-cancer effect of Nelfinavir" and suggests that this study "presents opportunities to optimize the drug as a targeted polypharmacology agent."

Over in PLoS Genetics, an international team led by investigators at the University of Toronto reports its analysis of a mouse model of the RIDDLE syndrome, a hereditary disease caused by mutations of human RNF168 that is "clinically characterized by radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties." The team shows that Rnf168−/− mice exhibit genomic instability, defective spermatogenesis, immunodeficiency, and are subject to increased risk of cancer, particularly as the "loss of Rnf168 … synergizes with p53 inactivation in promoting tumorigenesis." Among other things, the Toronto-led team says that its study sheds light on a "central role for RNF168 in the hierarchical network of DNA break signaling that maintains genomic integrity and suppresses cancer development in mammals."

Researchers at London's Royal Marsden Hospital and Institute of Cancer Research show that ESR1, which lies immediately upstream of recently reported breast cancer risk-associated SNPs on 6q25.1, is co-expressed with adjacent uncharacterized genes, the functions of which "may be important influences on the recently identified relationship between SNPs in this region and breast cancer risk." Indeed, the team says its array-based analysis suggests "that some of the biological effects previously attributed to ER could be mediated and/or modified by these co-expressed genes."

The Scan

Study Reveals New Details About Genetics of Major Cause of Female Infertility

Researchers in Nature Medicine conducted a whole-exome sequencing study of mote than a thousand patients with premature ovarian insufficiency.

Circulating Tumor DNA Shows Potential as Biomarker in Rare Childhood Cancer

A study in the Journal of Clinical Oncology has found that circulating tumor DNA levels in rhabdomyosarcoma may serve as a biomarker for prognosis.

Study Recommends Cancer Screening for Dogs Beginning Age Seven, Depending on Breed

PetDx researchers report in PLOS One that annual cancer screening for dogs should begin by age seven.

White-Tailed Deer Harbor SARS-CoV-2 Variants No Longer Infecting Humans, Study Finds

A new study in PNAS has found that white-tailed deer could act as a reservoir of SARS-CoV-2 variants no longer found among humans.