2013 · Nature
Circular RNAs are a large class of animal RNAs with regulatory potency
Verdict
UNSCIENTIFIC
Neither the paradigm nor the study inside it passes. The verdict is unscientific.
1·Study methodology · inside the paradigm
UNSCIENTIFIC
Does not follow the scientific method within Genomics / DNA Model.
2·Paradigm · Genomics / DNA Model
UNSCIENTIFIC
Fails the tests. The worse layer decides.
How the verdict is decided
The verdict grades both layers: the paradigm this study assumes, and how the study was carried out inside it. Both must be scientific for the whole thing to be scientific. A clean method inside an unscientific paradigm is unscientific. An unscientific method inside a better paradigm is unscientific. A split on either layer is mixed. The worse layer decides.
1·Study methodology
Did this study test its claim with methods that are independent, falsifiable, and non-circular?
UNSCIENTIFIC
This study claims that thousands of circular RNAs exist in animals and regulate gene activity by binding other RNA molecules, found by sequencing and computer analysis. All three tests fail.
Independently Verifiable
Fail
Sequencing machines produced fluorescent signals and software told them those signals were circular RNAs, but a stranger sees light and computer output, not circRNAs.
Falsifiable
Fail
The computational pipeline was built to find patterns the model calls circular RNA, and any failure to detect them would be blamed on low expression or wrong tissue rather than questioning whether circRNAs exist.
Non-Circular
Fail
The sequencing and analysis tools were built from the RNA model to detect what the model already named, and the detection was then called proof the model is correct.
Why
They took samples from humans, mice, and nematodes and ran them through chemistry and machines that the model assumes are reading RNA. The machines produced fluorescent signals, and software interpreted those signals as fragments of circular RNA. A computer matched the fragments against each other and found patterns the model calls head-to-tail splicing. They called the patterns evidence that thousands of circular RNAs exist. They injected material they called CDR1as into zebrafish embryos and saw impaired midbrain development. The impaired development is visible. The claim that a circular RNA caused it is the model narrating the injection. At no point did anyone see a circular RNA. They saw signals on a screen and a deformed fish, and the model connected the two.
2·Paradigm · Genomics / DNA Model
Does the framework this study assumes pass the three tests?
UNSCIENTIFIC
Independently Verifiable
Fail
Nobody has seen a gene, let alone watched one regulate anything; sequencing machines give off light and the model says the light is RNA.
Falsifiable
Fail
When sequencing finds nothing, the field calls it low expression, tissue specificity, or technical limitation, so no result can kill the claim that genes and RNAs exist and function.
Non-Circular
Fail
The sequencer, the reference genome, and the analysis software were all built from the DNA model and then used to confirm the DNA model.
Why
The DNA model says chemical fractions extracted from cells are a code that runs the body. Nobody has seen a gene, let alone watched one regulate anything. Sequencing machines give off flashes of light, and the model says the light is RNA being read. The reference genomes, the primers, and the analysis software were all built from the model and then used to confirm it. When a sequencing experiment finds nothing, the field calls it low expression, tissue specificity, or technical limitation. No result can kill the framework because every empty readout gets explained away as a problem with the run, not a problem with the model.
From the study
we sequenced and computationally analysed human, mouse and nematode RNA
We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression.
Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript.