Search bioRxiv⌕ Search

Biology subjects

Pathmendra, P.

Publications and source records attributed to Pathmendra, P..

4 recordsLinked to original sources

Verification of human nucleotide sequence reagents and cell line identities in original circRNA articles published in high impact factor journals

Numbers of research articles studying circRNAs have increased rapidly since 2017. Previous analyses of human circRNA articles in two high impact factor cancer research journals identified papers with wrongly identified nucleotide sequence reagents and circRNAs whose identities could not be independently verified. In the present study, verification of human nucleotide sequence reagent and cell line identities in retracted circRNA articles published from 2017-2021 in high impact factor journals found wrongly identified nucleotide sequences and/or cell lines in all 13 retracted papers. Similar analyses of human circRNA papers published in high impact factor journals in 2022 found wrongly identified, non-verifiable and/or questionable reagents in 71% (84/118) papers, where 51% (60/118) papers described at least one wrongly identified reagent. When individual error types and features of concern were considered, 2022 circRNA papers described wrongly identified nucleotide sequence reagents (52/118, 44%), questionable circRNA probes that did not meet accepted targeting requirements (34/118, 29%), non-verifiable nucleotide sequences (25/118, 21%), wrongly identified cell lines (22/118, 19%), and/or non-verifiable cell line identifiers (6/118, 5%). In summary, wrongly identified, non-verifiable and/or questionable reagents were unexpectedly frequent in human circRNA papers in high impact journals, highlighting the need for critical engagement with the circRNA literature.

genomics↗

Misspellings or miscellings- non-verifiable cell lines in cancer research publications

Reproducible laboratory research relies on correctly identified reagents. We have previously described human gene research papers with wrongly identified nucleotide sequence reagent(s), including papers studying miR-145. Manually verifying reagent identities in more recent miR-145 papers found 20/36 (56%) and 6/36 (17%) miR-145 papers with misidentified nucleotide sequence reagent(s) and human cell line(s), respectively. We also found 5 cell line identifiers in two miR-145 papers with wrongly identified nucleotide sequences and cell lines, and 18 identifiers published elsewhere that did not correspond to indexed cell lines. These cell line identifiers were described as non-verifiable, as their identities appeared uncertain. Studying 420 papers that mentioned 8 different non-verifiable cell line identifier(s) found 235 papers (56%) that appeared to refer to BGC-803, BSG-803, BSG-823, GSE-1, HGC-7901, HGC-803 and/or MGC-823 as independent cell lines. We could not find publications describing how these cell lines were established, and they were not indexed in claimed externally accessible cell line repositories. While some papers stated that STR profiles had been generated for BGC-803, GSE-1 and/or MGC-823 cells, no STR profiles were identified. In summary, non-verifiable human cell lines represent new challenges to research reproducibility and require further investigation to clarify their identities. Novelty and Impact StatementThrough verifying reagent identities in research publications, our team found 23 non-verifiable human cell line identifiers, most of which could represent misspellings of contaminated cancer cell lines. Of 8 identifiers studied in detail, 7 non-verifiable identifiers were unexpectedly referred to as independent cell lines across 235 publications. We therefore describe a process "miscelling", where published cell lines lack descriptions of how they were established, cannot be found in claimed external repositories and lack STR profiles.

cancer biology↗

Verification of nucleotide sequence reagent identities in original publications in high impact factor cancer research journals

Human gene research studies that describe wrongly identified nucleotide sequence reagents have been mostly identified in journals of low to moderate impact factor, where unreliable findings could be considered to have limited influence on future research. This study examined whether papers describing wrongly identified nucleotide sequences are also published in high impact factor cancer research journals. We manually verified nucleotide sequence identities in original Molecular Cancer articles published in 2014, 2016, 2018 and 2020, including nucleotide sequence reagents that were claimed to target circRNAs. Using keywords identified in problematic 2018 and 2020 Molecular Cancer papers, we also verified nucleotide sequence identities in 2020 Oncogene papers that studied miRNA(s) and/or circRNA(s). Overall, 3.8% (253/6,647) and 4.3% (50/1,165) nucleotide sequences that were verified in Molecular Cancer and Oncogene papers, respectively, were found to be wrongly identified. These wrongly identified nucleotide sequences were distributed across 18% (92/500) original Molecular Cancer papers, including 38% Molecular Cancer papers from 2020, and 40% (21/52) selected Oncogene papers from 2020. Original papers with wrongly identified nucleotide sequences were therefore unexpectedly frequent in two high impact factor cancer research journals, highlighting the risks of employing journal impact factors or citations as proxies for research quality.

cancer biology↗

Human gene function publications that describe wrongly identified nucleotide sequence reagents are unacceptably frequent within the genetics literature

Nucleotide sequence reagents underpin a range of molecular genetics techniques that have been applied across hundreds of thousands of research publications. We have previously reported wrongly identified nucleotide sequence reagents in human gene function publications and described a semi-automated screening tool Seek & Blastn to fact-check the targeting or non-targeting status of nucleotide sequence reagents. We applied Seek & Blastn to screen 11,799 publications across 5 literature corpora, which included all original publications in Gene from 2007-2018 and all original open-access publications in Oncology Reports from 2014-2018. After manually checking the Seek & Blastn screening outputs for over 3,400 human research papers, we identified 712 papers across 78 journals that described at least one wrongly identified nucleotide sequence. Verifying the claimed identities of over 13,700 nucleotide sequences highlighted 1,535 wrongly identified sequences, most of which were claimed targeting reagents for the analysis of 365 human protein-coding genes and 120 non-coding RNAs, respectively. The 712 problematic papers have received over 17,000 citations, which include citations by human clinical trials. Given our estimate that approximately one quarter of problematic papers are likely to misinform or distract the future development of therapies against human disease, urgent measures are required to address the problem of unreliable gene function papers within the literature. Author summaryThis is the first study to have screened the gene function literature for nucleotide sequence errors at the scale that we describe. The unacceptably high rates of human gene function papers with incorrect nucleotide sequences that we have discovered represent a major challenge to the research fields that aim to translate genomics investments to patients, and that commonly rely upon reliable descriptions of gene function. Indeed, wrongly identified nucleotide sequence reagents represent a double concern, as both the incorrect reagents themselves and their associated results can mislead future research, both in terms of the research directions that are chosen and the experiments that are undertaken. We hope that our research will inspire researchers and journals to seek out other problematic human gene function papers, as we are unfortunately concerned that our results represent the tip of a much larger problem within the literature. We hope that our research will encourage more rigorous reporting and peer review of gene function results, and we propose a series of responses for the research and publishing communities.

genetics↗