A project to identify studies doomed by problematic reagents has triggered three more retractions, bringing the total to five.
Jennifer Byrne, a scientist at the University of Sydney, who developed the the idea of double-checking the nucleic acid sequences of research materials — thereby ensuring studies were testing the gene in question — told Retraction Watch that all three retractions came after she started emailing journals in January to alert them to the problems:
We had a list of 43 papers we’ve been writing emails about. We’ve found more. There are a lot of these papers. In terms of total numbers, conservatively, we’re talking about hundreds…
The presence of incorrect nucleotide sequences in papers may serve to highlight other concerns as well.
Two journals have recently retracted papers that Byrne and Labbé have flagged. BioMed Research International (BMRI) retracted two papers and The Korean Journal of Physiology & Pharmacology retracted one. The extra scrutiny has also raised allegations of image duplication and plagiarism in these papers.
Byrne and Cyril Labbé, a French computer scientist, presented an update on their project at this week’s Peer Review Congress in Chicago. They’re now developing semi-automated software that extracts the sequences of these kinds of reagents, as presented in a given paper, and then feeds that into the basic local alignment search tool (BLAST) to check that the sequences match the intended gene (or not, if it’s meant to be used as a negative control).
Readers may recall that we wrote about the duo’s work in January, after they published an article in Scientometrics on a series of oncology papers they showed had used a negative control that did target a particular gene associated with several cancers. Byrne told us that instead of special software, she and Labbé had used a manual search in Google Scholar to find potentially problematic papers. At that time, two papers in the series had been retracted.
Two of the recent retractions were mentioned in the Scientometrics article — one in BMRI and one in the Korean Journal of Physiology & Pharmacology.
Matt Hodgkinson, head of research integrity at Hindawi, which publishes BMRI, told us:
Spotting inconsistencies and patterns in articles using automated tools is promising for correcting the literature and preventing problematic articles from being published.
“Long Noncoding RNA KIAA0125 Potentiates Cell Migration and Invasion in Gallbladder Cancer,” originally published in September 2015, has been cited six times, according to Clarivate Analytics’ Web of Science.
This paper was one in the series of the articles identified by Byrne and Labbé in Scientometrics; like the others it used an improper negative control. The retraction notice added that it appeared “very similar” to the other articles in the series.
Hodgkinson told us that the authors agreed to the retraction.
In addition to the problems related to the controls, several figures were duplicated. The authors said that one case, where panels within the same figure were duplicated, was “due to carelessness.” In the other instance, control panels were duplicated from another article by the same authors, and not cited. The notice reported that the authors said those experiments were:
…performed simultaneously, so they shared the same controls.
The other BMRI paper, “High Expression of PTGR1 Promotes NSCLC Cell Growth via Positive Regulation of Cyclin-Dependent Protein Kinase Complex,” was retracted Aug. 28. Originally published in BMRI June 26, 2016, it has not yet been cited.
In the notice, the journal said this paper, too, seemed to fit into the “series” of problematic papers identified by Byrne and Labbé:
the intertextual distance between this article and an article in the series is lower than expected by chance.
The journal added that it tried to communicate with the authors, but they did not respond.
The third paper, “Myosin VI contributes to malignant proliferation of human glioma cells,” was published Feb. 23, 2016 in the Korean Journal of Physiology & Pharmacology and retracted Aug. 22. It has been cited three times.
That notice raised the possibility that the authors hadn’t actually performed the experiments, an allegation they denied. Still, they agreed to the retraction, the notice said:
Although the corresponding author, Ping Zhong, claimed the experiments were performed by their team and the data collected were true and valid, not fabricated, all authors have admitted that they used inaccurate methods (inaccurate use of shRNA sequences) and inappropriate presentations of the article (plagiarism). All authors have agreed that retraction from the literature is the best corrective action to the scientific community, and apologize to the Editors and readership of Korean J Physiol Pharmacol.
Byrne told us that while it’s easy to find papers with mismatched reagents, it’s hard to prove that they’re problematic. At the Peer Review Congress, she and Labbé presented their efforts to make the process more automated, but the candidate papers identified by the algorithm still have to be fact-checked manually, Byrne said:
That takes a lot of time. We have a cohort of several hundred that we are still going through and checking.
Even harder is getting the journals to take action. Byrne said Hindawi responded “almost immediately” to her January emails, but others haven’t been so responsive.
“Some journals are investigating,” she told us. “Some have not replied.”
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This a very welcome development. Misguided oligonucleotide primers are not all that rare in publications, specifically in real-time PCR they may amount to 1 in 10 being wrong strand or even wrong gene. Here is a peculiar case highlighted in PubPeer
https://pubpeer.com/publications/775D1EAE91E1929E4D49AB577A9314#1