Monthly Archives: April 2013

Reporting standards to enhance article reproducibility

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Beginning May 1st Nature Methods will be requiring authors of manuscripts being sent back to peer review to fill out a checklist to disclose technical and statistical information about their submission.

The May Editorial briefly describes why we are using this checklist and provides some details of what is included. Authors can find the checklist that Nature Methods will be using at https://www.nature.com/nmeth/pdf/sm_checklist.pdf and there is a link to it on the journal homepage. Our checklist is identical to that of most of the other Nature journals except for an added item asking authors to “Identify all custom software or scripts that were required to implement the methodology being described and where in the procedures each was used.” Based on feedback we have received, a missing software or script seems to be the item most often mentioned by people commenting on challenges in reproducing a method we have published. This reporting requirment is an important step in trying to address this deficiency.

We expect that the addition of these reporting requirements will elict some grumbling by authors. But based on the experience of Nature Neuroscience, which has been requiring authors to fill out a methods checklist before even the first round of review, we expect authors will come to appreciate the role it serves.

The checklist is only one part of the efforts the Nature journals are making to improve reproducibility. The other journals are also removing formal limits on the length of the methods section. But since Nature Methods has long had no limits on the length of our Methods section, the checklist is the most prominant change for us and our authors.

The May issue also contains other articles relevant to reproducibility. The Correspondence section has a discussion about analyzing the reproducibility of animal experiments. And the May Technology Feature discusses reproducibility in quantitative PCR, a methodology that has suffered from serious problems in this regard due to poor experimental technique and reporting.

For those not tired of reproducibility at this point Nature also has a Special Focus on Challenges in irreproducible research.

As has been said in the editorials on the subject, this is only a first step toward improving the reproducibility of our published research and we welcome feedback from the community on our efforts.

Scientists rally as sequester-based budget cuts loom

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Vivien Marx reports from the AACR meeting and Rally for Medical Research in Washington, with details of the AACR plenary address by Harold Varmus.

Leaving the talks and conference halls behind, around 8,000 researchers and clinicians attending the American Association of Cancer Research (AACR) in Washington, DC joined patients and patient advocates on the Carnegie Library grounds to rally against cuts to research budgets. Members of Congress, patient advocates and celebrities involved in the organization Stand Up to Cancer, which also funds research, made their loud and forceful case against sequestration, the impending across-the-board forced 5% budget cuts facing government agencies, including the US National Institutes of Health.

Rally participant, University of Wisconsin scientist Nihal Ahmad, says that the sequester is already hitting his research, cutting into his ability to buy tools and reagents, which is work on signal transduction in tumors.

Overcoming cancer is a “very significant outcome for this country,” says Daniel Pollay of Weill Cornell Medical Center, explaining why he attended the rally. Andrea Russello, a product scientist at Cell Signaling Technology took part in the rally because her customers include academic scientists whose work is being affected by the sequester. She also knows many young scientists who cannot find jobs after their post-doctoral fellowships. The risk now is not just a budget plateau. “I think we’ll really regress if we can’t keep pushing forward,” she says.

Columbia University Medical Center researcher Jeanine D’Armiento looks at matrix metalloproteinases in tumors, in lung diseases in particular. Her latest grant scored in the 9th percentile. “Last year funding was at 10% and now it’s at 6%, if it were last year I would have received that grant. But right now, I don’t have it.” Staff cuts have been inevitable and she feels that her dream to move from mouse models into humans has to be put indefinitely on hold. According to NIH rules, the grant can only be resubmitted after 36 months.

Prior to the rally, National Cancer Institute Director Harold Varmus in his AACR plenary address encouraged delegates to attend it in order to highlight the importance of doing science to counter illness. The new BRAIN Initiative proposed by President Obama, may bode well for the future of science, he says, but it is an initiative that will “come too late” to address the problems cancer researchers face this fiscal year and the near future, he says.

Instead of just a fall over a fiscal cliff, research funding has actually been declining since 2003, he says. Inflation has eroded the agency’s spending ability to 2001 levels.

At the same time, he feels optimism about the new inroads against cancer that researchers are making and the possibilities the current $4.8 billion dollar budget provides. To manage the sequestration, his agency will keep the number of funding grants constant this year with a grant-funding success rate around 13%-14%.

He also took the opportunity to talk about initiatives the NCI is rolling out, also as a way to manage sequestration. The NCI is rolling out new initiatives geared toward ‘precision medicine’, including:

  • A Cancer Knowledge Commons, which is an informatics-based approach to aggregating data from many sources, will help to promote the use genomic analysis to improve research, treatment and outcomes.
  • A new Center for Cancer Genomics to continue the work of such projects as the The Cancer Genome Atlas
  • Clinical trials that find drugs that match the genomic profile of patients to drugs that stand to help them.
  • Continuation of the Provocative Questions Initiative, which is geared toward unanswered questions related to the biology of cancer and which are high risk but are also high reward opportunities.
  • A focus on RAS mutations, which are found in around one quarter of all tumors, leveraging proteomics and immunotherapies.
  • Looking at new ways to perform pre-clinical testing of drugs.
  • Global health initiatives.
  • Programs that take on the cultural change across the research community necessary to allow better sharing of results, reagents and reporting of outcomes from clinical trials.

An era for BRAIN technology

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President Barack Obama has just proposed large investments in a project aiming to develop technologies that enhance our understanding of brain function.

In an official announcement from the White House, US President Obama just launched the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative project. This basic research project is expected to receive large sums of public and private funding to promote technologies that expand our knowledge of brain function.

This was a much awaited announcement. From what can be read in the White House’s official Press release, the BRAIN Initiative will be a collaboration between the US National Institutes of Health, the Defense Advanced Research Projects Agency and the National Science Foundation, with an initial injection of funds going up to $100 million for 2014.

To set the goals and timeline of this project, the NIH will establish a working group composed of 60-80 scientists co-chaired by Cori Bargmann of Rockefeller University and Bill Newsome from Stanford University. Through workshops and meetings that will take place in 2013, the working group will define the detailed scientific goals and establish a multi-year scientific plan for achieving them. The workshops are to start in about one month.

In addition, the project will have several private sector partners: the Allen Institute for Brain Science, the Howard Hughes Medical Institute (HHMI), the Kavli Foundation and the Salk Institute for Biological Studies. Most of these institutions have already been investing in technology development to address the challenges of understanding the brain for some time. In fact, Nature Methods recently published work from HHMI investigators showing the first whole brain imaging of neural activity at the single-cell level. As the details of the goals and timelines of the BRAIN Initiative become clearer over the next few months, we will likely have a more concrete idea of how the budget for BRAIN will be projected in the coming years.

What is unique about BRAIN compared to other previous ‘big science’ projects like the Human Genome Project is that it is advocating for technology development first as it lays out its broad goals without indicating a particular biological idea or concept. The need for technology development is so dear in neuroscience that in our view devoting substantial resources to this is essential for understanding brain function, a view that appears to be shared by the HHMI as evidenced by the substantial technology development they are funding for brain research at the HHMI Janelia Farm Research campus.

As we have discussed in previous posts on this site and in our April Editorial, to understand the brain we will need technologies that help large scale mapping of the structural wiring diagrams in the brain, that record the activity of whole brains in action at resolutions that mirror those of physiology and behavior and that link function and behavior. In all these areas, we first need to improve our tools and methods.

The progress that can be made by promoting technological development cannot be underestimated. Once more powerful methods are in the hands of researchers, knowledge will advance at a much higher speed and investments in science will be more productive and efficient.