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Circular RNAs are really "hot" these days. But, one should keep in mind that the amount of virtually all circular RNAs is lower in cancer (compared to non-cancerous adjacent normal tissue), thus they are not very promising as biomarkers. Also, their biological role is unclear. We did comprehensive literature review on this topic and found nothing truly convincing.

A well established principal investigator said this to his lab during a crisis "we are out of money" meeting: "We are all in the same boat, but only I have a parachute"

Are you suggesting scientists are "goverment contractors"? Never thought of myself as one.

Certainly there are such scientists. There is a very strong incentive for researchers to be novel and make discoveries "out of the box" - how much of these discoveries will be published, and will stand the test of time is a very different thing. Almost every single cancer case we see in our clinical sequencing effort has one or more mutations in a limited set of the "usual suspects" <500 protein coding genes. We are at a stage, where it is more difficult to find a new oncogene or tumor suppressor gene than to suggest an "out of the box" mechanism based on pre-clinical data.

The absolute error-rate is not really a problem if the errors are random and you have the budget to sequence enough independent fragments. Sequencing becomes tricky (both Sanger and next-gen) because of non-random recurrent artifacts associated with the sequencing method or molecular manipulations done to the DNA or RNA.

Thousands of new life-science publications appear each day on PubMed. It is quite hard to keep up, but it is possible to set up: - keyword-triggered RSS-feeds at NCBI - an account on Google Scholar which has some "intelligent" notifications. - or finally use Sciencescape: https://sciencescape.org

> your peer group has even looked at this.

I think it will help most if I explain the incentives for scientists (at least in the US). From their first day in the lab scientists are rewarded most for generating data and making discoveries. The more novel and paradigm shifting the discovery the better - as it opens the door to high-impact publications and future research money. But "extraordinary claims require extraordinary evidence" and the more unexpected the finding the more difficult it is to convince your peers and get it published.

Somewhat idealistically, this has two consequences for a good lead scientist: 1) hew will guide his lab to explore the unexplored 2) and subject the most novel and promising findings to the most stringent experimental verification.

So the answer to your direct question - yes probably someone somewhere tried to test the iodine-breast cancer hypothesis, but since it is not a major topic in breast cancer research the experiments have probably failed and were not published and thus independently replicated

The cancer research and cancer epidemiology communities do not really talk to each other (as a cancer researcher for many years I have never been to an epidemiology seminar despite working in a 'cancer center'). So it is really a fight for money and mind influence. Most cancer researchers lean towards drugs targeting molecular mechanisms of cancer, cancer epidemiologists, on the other hand, aim for political decisions that combat environmental factors. Where should most money go? what should be discussed in the media?

Vogelstein proposes a simple model that explains a lot of data. Sure, the implications are bleak, but the scientists I talked to were not really surprised that it finally got out.

Author of PaPy here.

Thanks for giving PaPy a try. Although PaPy [https://github.com/mcieslik-mctp/papy] has never gained traction :(, I have been using it daily for over 5 years (no bugs in the scheduler so far). By now our PaPy based genomics pipelines have probably processed petabytes of data.