RNA studies under fire
High-profile results challenged over statistical analysis of sequence data.
Erika Check Hayden
25 April 2012
High-throughput RNA sequencing has yielded some unexpected results in the past few years — including some that seem to rewrite conventional wisdom in genetics. But a few of those findings are now being challenged, as computational biologists warn of the statistical pitfalls that can lurk in data-intensive studies.
The latest case centres on imprinted genes. Humans and most other animals inherit two copies of most genes, one from each parent. But in some cases, only one copy is expressed; the other copy is silenced. In such cases, the gene is described as being imprinted. In July 2010, a team led by Catherine Dulac and Christopher Gregg, both then at Harvard University in Cambridge, Massachusetts, published a study1 in Science estimating that 1,300 mouse genes — an order of magnitude more than previously known — were imprinted.
Now, researchers are arguing that a flawed analysis led Dulac and Gregg to vastly overestimate imprinting in their paper. “The reason this paper was published in Scienceis that they made this big claim that they saw an order-of-magnitude more genes that are imprinted, and I don’t think that’s true,” says Tomas Babak, a computational biologist at Stanford University in California, who challenged the study in a paper2 published on 29 March.
Dulac counters that she and her team “absolutely stand by those data”, adding that they have confirmed some of their findings by other means. The situation resembles an ongoing debate over another RNA-sequencing paper3 published in 2011. In that study, Vivian Cheung of the University of Pennsylvania in Philadelphia and her colleagues reported evidence that RNA editing — which creates differences between a gene’s DNA sequence and the RNA sequence it gives rise to — is “widespread” in the human genome. RNA editing had been seen before, but the finding that it was so frequent challenges the central dogma, which holds that an organism’s genes are transcribed faithfully.
Other scientists have argued that Cheung’s results arose largely from errors in data analysis and that the true extent of RNA editing is probably no greater than previously thought4. Cheung did not respond to Nature’s request for comment on this story, but she has stood by her results.
...High-profile results challenged over statistical analysis of sequence data.
Erika Check Hayden
25 April 2012
High-throughput RNA sequencing has yielded some unexpected results in the past few years — including some that seem to rewrite conventional wisdom in genetics. But a few of those findings are now being challenged, as computational biologists warn of the statistical pitfalls that can lurk in data-intensive studies.
The latest case centres on imprinted genes. Humans and most other animals inherit two copies of most genes, one from each parent. But in some cases, only one copy is expressed; the other copy is silenced. In such cases, the gene is described as being imprinted. In July 2010, a team led by Catherine Dulac and Christopher Gregg, both then at Harvard University in Cambridge, Massachusetts, published a study1 in Science estimating that 1,300 mouse genes — an order of magnitude more than previously known — were imprinted.
Now, researchers are arguing that a flawed analysis led Dulac and Gregg to vastly overestimate imprinting in their paper. “The reason this paper was published in Scienceis that they made this big claim that they saw an order-of-magnitude more genes that are imprinted, and I don’t think that’s true,” says Tomas Babak, a computational biologist at Stanford University in California, who challenged the study in a paper2 published on 29 March.
Dulac counters that she and her team “absolutely stand by those data”, adding that they have confirmed some of their findings by other means. The situation resembles an ongoing debate over another RNA-sequencing paper3 published in 2011. In that study, Vivian Cheung of the University of Pennsylvania in Philadelphia and her colleagues reported evidence that RNA editing — which creates differences between a gene’s DNA sequence and the RNA sequence it gives rise to — is “widespread” in the human genome. RNA editing had been seen before, but the finding that it was so frequent challenges the central dogma, which holds that an organism’s genes are transcribed faithfully.
Other scientists have argued that Cheung’s results arose largely from errors in data analysis and that the true extent of RNA editing is probably no greater than previously thought4. Cheung did not respond to Nature’s request for comment on this story, but she has stood by her results.
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