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This Week in Nature: Jul 26, 2012

In papers published online in advance in Nature this week, three international research teams discuss the genomic complexity of medulloblastoma. One team, led by German Cancer Research Center's David Jones, reports having sequenced and analyzed 125 tumor-normal pairs. Another team, led by the Broad Institute's Trevor Pugh, reports having used whole-exome hybrid capture and deep sequencing to identify somatic mutations in 92 primary medulloblastoma-normal pairs. And a third team, led by Paul Northcott at the Hospital for Sick Children in Toronto, reports on its investigation of somatic copy number aberrations in 1,087 medulloblastomas. As Daily Scan's sister publication GenomeWeb Daily News reports, "analyses of the exomes — each sequenced to a depth of 106-fold, on average — uncovered a median of 16 somatic mutations per tumor. Not surprisingly, the mutation and copy number profiles varied across the molecularly defined medulloblastoma subtypes, known as WNT, SHH, Group 3, and Group 4." Our sister blog Cancer Minute also has more on these studies.

Researchers at the Austrian Academy of Sciences' Institute of Molecular Biotechnology and their colleagues this week show that deficiency of the murine angiotensin I converting enzyme 2, or Ace2, "results in highly increased susceptibility to intestinal inflammation induced by epithelial damage." Further, the team reports that "transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis." The researchers add that dietary tryptophan can directly regulate ACE2-dependent changes in epithelial immunity and the gut microbiota in such mice.

Massachusetts General Hospital's Daniel MacArthur says false positives are all but inevitable in genomics research. "In fact, it has never been easier to generate high-impact false positives than in the genomic era, in which massive, complex biological data sets are cheap and widely available," he writes in an opinion article appearing in this week's Nature. "To be clear, the majority of genome-scale experiments yield real results, many of which would be impossible to uncover through targeted hypothesis-driven studies." To MacArthur's mind, "two processes conspire to delude ambitious genomicists." One, he says, is that because the genome is so large "that highly unusual events occur by chance much more often than we would intuitively expect." The other is that every high-throughput technology has its nuances — "error modes and systematic biases that, to the unwary eye, can seem like interesting biology," MacArthur writes.

In a related editorial, Nature points to competition within the community as a large factor in the the push to publish potential false-positives, and a steady rise in retractions in recent years. "Much of this sloppy science comes from the pressure to generate 'surprising' results and to publish them quickly, even though they are more likely to be driven by errors than are findings that more or less follow from previous work," Nature says. "A researcher who reveals something exciting is more likely to get a high-profile paper (and a permanent position) than is someone who spends years providing solid evidence for something that everyone in the field expected to be true."

The Scan

Mosquitos Genetically Modified to Prevent Malaria Spread

A gene drive approach could be used to render mosquitos unable to spread malaria, researchers report in Science Advances.

Gut Microbiomes Allow Bears to Grow to Similar Sizes Despite Differing Diets

Researchers in Scientific Reports find that the makeup of brown bears' gut microbiomes allows them to reach similar sizes even when feasting on different foods.

Finding Safe Harbor in the Human Genome

In Genome Biology, researchers present a new approach to identify genomic safe harbors where transgenes can be expressed without affecting host cell function.

New Data Point to Nuanced Relationship Between Major Depression, Bipolar Disorder

Lund University researchers in JAMA Psychiatry uncover overlapping genetic liabilities for major depression and bipolar disorder.