The thin ret(raction) line: biomedical journal responses to incorrect non-targeting nucleotide sequence reagents in human gene knockdown publications

Abstract

The capacity of the scientific literature to self-correct is of vital importance, but few studies have compared post-publication journal responses to specific error types. We have compared journal responses to a specific reagent error in 31 human gene knockdown publications, namely a non-targeting or negative control nucleotide sequence that is instead predicted to target a human gene. The 31 papers published by 13 biomedical journals generated 26 published responses (14 retractions, 5 expressions of concern, 7 author corrections which included one resolved expression of concern) as well as 6 stated decisions to take no action. Variations in published responses were noted both between journals and by 4 journals that published different responses to at least 2 papers. A subset of published responses revealed conflicting explanations for the wrongly identified control reagent, despite 30/31 papers obtaining their gene knockdown reagents from the same external supplier. Viewed collectively, different journal responses to human gene knockdown publications with a common reagent error type suggest that editorial staff require more support to interpret post-publication notifications of incorrect nucleotide sequence reagents. We propose a draft template to facilitate the communication, interpretation and investigation of published errors, including errors affecting research reagents.

Identification of human gene research articles with wrongly identified nucleotide sequences

“…Experiments that analyse individual genes typically require nucleotide sequence reagents as either targeting and/or control reagents ( 8 , 11 ). As nucleotide sequence identities cannot be deduced by eye, DNA or RNA reagent sequences must be paired with text descriptions of their genetic identities and experimental use ( 8 , 11 , 12 , 13 ). The integrity of reported experiments therefore requires both the identities of nucleotide sequence reagents and their text descriptions to be correct ( 11 , 12 ).…”

“…As nucleotide sequence identities cannot be deduced by eye, DNA or RNA reagent sequences must be paired with text descriptions of their genetic identities and experimental use ( 8 , 11 , 12 , 13 ). The integrity of reported experiments therefore requires both the identities of nucleotide sequence reagents and their text descriptions to be correct ( 11 , 12 ). Accurate reporting of nucleotide sequence reagents is also critical to permit reagent reuse across different experiments and publications ( 11 ).…”

“…The integrity of reported experiments therefore requires both the identities of nucleotide sequence reagents and their text descriptions to be correct ( 11 , 12 ). Accurate reporting of nucleotide sequence reagents is also critical to permit reagent reuse across different experiments and publications ( 11 ). The ubiquitous description of nucleotide sequence reagents within the biomedical and genetics literature, combined with the routine pairing of nucleotide sequences and text identifiers, are likely to contribute to tacit assumptions that reported nucleotide sequence reagents are correctly identified.…”

“…The ubiquitous description of nucleotide sequence reagents within the biomedical and genetics literature, combined with the routine pairing of nucleotide sequences and text identifiers, are likely to contribute to tacit assumptions that reported nucleotide sequence reagents are correctly identified. However, as nucleotide sequences cannot be understood by eye, we have proposed that nucleotide sequence reagents are susceptible to different types of errors ( 8 , 11 , 12 ). These error types represent the equivalent of spelling errors ( 12 , 14 , 15 ), as well as identity errors, where a correct sequence is replaced by a different and possibly genetically unrelated sequence ( 11 , 12 , 13 , 16 , 17 , 18 , 19 , 20 , 21 ).…”

“…However, as nucleotide sequences cannot be understood by eye, we have proposed that nucleotide sequence reagents are susceptible to different types of errors ( 8 , 11 , 12 ). These error types represent the equivalent of spelling errors ( 12 , 14 , 15 ), as well as identity errors, where a correct sequence is replaced by a different and possibly genetically unrelated sequence ( 11 , 12 , 13 , 16 , 17 , 18 , 19 , 20 , 21 ).…”