Cited by 124Sex and Gender in Healthcarescientometrics and bibliometrics researchMeta-analysis and systematic reviews

Bias in the reporting of sex and age in biomedical research on mouse models

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Flórez-Vargas, Oscar, Brass, Andy, Karystianis, George, Bramhall, Michael, Stevens, Robert, Cruickshank, Sheena, Nenadic, Goran·2016·eLife

Abstract

In animal-based biomedical research, both the sex and the age of the animals studied affect disease phenotypes by modifying their susceptibility, presentation and response to treatment. The accurate reporting of experimental methods and materials, including the sex and age of animals, is essential so that other researchers can build on the results of such studies. Here we use text mining to study 15,311 research papers in which mice were the focus of the study. We find that the percentage of papers reporting the sex and age of mice has increased over the past two decades: however, only about 50% of the papers published in 2014 reported these two variables. We also compared the quality of reporting in six preclinical research areas and found evidence for different levels of sex-bias in these areas: the strongest male-bias was observed in cardiovascular disease models and the strongest female-bias was found in infectious disease models. These results demonstrate the ability of text mining to contribute to the ongoing debate about the reproducibility of research, and confirm the need to continue efforts to improve the reporting of experimental methods and materials.

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  • Evidence shows that the majority of publications fail to include key information and there is significant scope to improve the reporting of studies involving animal research.

    “However, evidence shows that the majority of publications fail to include key information and there is significant scope to improve the reporting of studies involving animal research [1–4].”

    From Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0 (2020) · cites this paper as [2]

    The Results (‘Reporting of sex and age’; page not available) say that only about 50% of mouse-model papers published since 2012 reported both variables. The Discussion identifies this as a reporting problem, but the study does not establish that a majority of animal-research publications generally omit key information. (LLM, conf=0.86)

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References 57 · Cited by 124

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  1. Ananiadou S Kell DB Tsujii J 2006 Text mining and its potential applications in systems biology Trends in Biotechnology 24 571 579 10.1016/j.tibtech.2006.10.002 17045684 · DOI
  2. Arbogast P Glösmann M Peichl L 2013 Retinal cone photoreceptors of the deer mouse peromyscus maniculatus: development, topography, opsin expression and spectral tuning PLoS ONE 8 e13615 10.1371/journal.pone.0080910 PMC3829927 24260509 · DOI
  3. Arnold AP 2010 Promoting the understanding of sex differences to enhance equity and excellence in biomedical science Biology of Sex Differences 1 1 10.1186/2042-6410-1-1 21208467 PMC3010102 · DOI
  4. Baker D Lidster K Sottomayor A Amor S 2014 Two years later: journals are not yet enforcing the ARRIVE guidelines on reporting standards for pre-clinical animal studies PLoS Biology 12 e13615 10.1371/journal.pbio.1001756 PMC3883646 24409096 · DOI · Paper page
  5. Beery AK Zucker I 2011 Sex bias in neuroscience and biomedical research Neuroscience and Biobehavioral Reviews 35 565 572 10.1016/j.neubiorev.2010.07.002 20620164 PMC3008499 · DOI · Paper page
  6. Bramhall M Flórez-Vargas O Stevens R Brass A Cruickshank S 2015 Quality of methods reporting in animal models of colitis Inflammatory Bowel Diseases 21 1248 1259 10.1097/MIB.0000000000000369 25989337 PMC4450905 · DOI
  7. Burden N Chapman K Sewell F Robinson V 2015 Pioneering better science through the 3Rs: an introduction to the national centre for the replacement, refinement, and reduction of animals in research (NC3Rs) Journal of the American Association for Laboratory Animal Science: JAALAS 54 198 208 25836967 PMC4382625
  8. Case LK Wall EH Dragon JA Saligrama N Krementsov DN Moussawi M Zachary JF Huber SA Blankenhorn EP Teuscher C 2013 The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease Genome Research 23 1474 1485 10.1101/gr.156703.113 23800453 PMC3759723 · DOI
  9. Clutton-Brock TH Isvaran K 2007 Sex differences in ageing in natural populations of vertebrates Proceedings of the Royal Society B: Biological Sciences 274 3097 3104 10.1098/rspb.2007.1138 17939988 PMC2293943 · DOI
  10. Cohen AM Hersh WR 2005 A survey of current work in biomedical text mining Briefings in Bioinformatics 6 57 71 10.1093/bib/6.1.57 15826357 · DOI
  11. Collins FS Tabak LA 2014 Policy: NIH plans to enhance reproducibility Nature 505 612 613 10.1038/505612a 24482835 PMC4058759 · DOI · Paper page
  12. Cunningham H Tablan V Roberts A Bontcheva K 2013 Getting more out of biomedical documents with GATE's full lifecycle open source text analytics PLoS Computational Biology 9 e13615 10.1371/journal.pcbi.1002854 PMC3567135 23408875 · DOI
  13. Dehlendorff C Andersen KK Olsen TS 2015 Sex disparities in stroke: women have more severe strokes but better survival than men Journal of the American Heart Association 4 10.1161/JAHA.115.001967 PMC4608080 26150479 · DOI
  14. Diedrich M Tadic J Mao L Wacker MA Nebrich G Hetzer R Regitz-Zagrosek V Klose J 2007 Heart protein expression related to age and sex in mice and humans International Journal of Molecular Medicine 20 865 874 10.3892/ijmm.20.6.865 17982696 · DOI
  15. Fleuren WW Alkema W 2015 Application of text mining in the biomedical domain Methods 74 97 106 10.1016/j.ymeth.2015.01.015 25641519 · DOI
  16. Flórez-Vargas O Bramhall M Noyes H Cruickshank S Stevens R Brass A 2014 The quality of methods reporting in parasitology experiments PloS One 9 e13615 10.1371/journal.pone.0101131 PMC4116335 25076044 · DOI
  17. Gemmell NJ Metcalf VJ Allendorf FW 2004 Mother's curse: the effect of mtDNA on individual fitness and population viability Trends in Ecology & Evolution 19 238 244 10.1016/j.tree.2004.02.002 16701262 · DOI
  18. Gilks WP Abbott JK Morrow EH 2014 Sex differences in disease genetics: evidence, evolution, and detection Trends in Genetics 30 453 463 10.1016/j.tig.2014.08.006 25239223 · DOI
  19. Herlyn M Fukunaga-Kalabis M 2010 What is a good model for melanoma? Journal of Investigative Dermatology 130 911 912 10.1038/jid.2009.441 20231823 · DOI
  20. Hotho A Numberger A Paab G 2005 A brief survey of text mining LDV Forum – GLDV Journal for Computational Linguistics and Language Technology 20 19 62
  21. ICMJE 2013 Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publications http://www.icmje.org/icmje-recommendations.pdf 15695967
  22. Ji H Zheng W Wu X Liu J Ecelbarger CM Watkins R Arnold AP Sandberg K 2010 Sex chromosome effects unmasked in angiotensin II-induced hypertension Hypertension 55 1275 1282 10.1161/HYPERTENSIONAHA.109.144949 20231528 PMC2905778 · DOI
  23. Kilkenny C Browne WJ Cuthill IC Emerson M Altman DG 2010 Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research PLoS Biology 8 e13615 10.1371/journal.pbio.1000412 PMC2893951 20613859 · DOI · Paper page
  24. Kilkenny C Parsons N Kadyszewski E Festing MF Cuthill IC Fry D Hutton J Altman DG 2009 Survey of the quality of experimental design, statistical analysis and reporting of research using animals PloS One 4 e13615 10.1371/journal.pone.0007824 PMC2779358 19956596 · DOI · Paper page
  25. Li J Kannan M Trivett AL Liao H Wu X Akagi K Symer DE 2014 An antisense promoter in mouse L1 retrotransposon open reading frame-1 initiates expression of diverse fusion transcripts and limits retrotransposition Nucleic Acids Research 42 4546 4562 10.1093/nar/gku091 24493738 PMC3985663 · DOI
  26. Lin CQ Dempsey PJ Coffey RJ Bissell MJ 1995 Extracellular matrix regulates whey acidic protein gene expression by suppression of TGF-alpha in mouse mammary epithelial cells: studies in culture and in transgenic mice Journal of Cell Biology 129 1115 1126 7744960 PMC2120484
  27. Maklakov AA Lummaa V 2013 Evolution of sex differences in lifespan and aging: causes and constraints BioEssays 35 717 724 10.1002/bies.201300021 23733656 · DOI · Paper page
  28. McCullough LD de Vries GJ Miller VM Becker JB Sandberg K McCarthy MM 2014 NIH initiative to balance sex of animals in preclinical studies: generative questions to guide policy, implementation, and metrics Biology of Sex Differences 5 15 10.1186/s13293-014-0015-5 25780556 PMC4360141 · DOI
  29. Mozaffarian D Benjamin EJ Go AS Arnett DK Blaha MJ Cushman M de Ferranti S Després JP Fullerton HJ Howard VJ Huffman MD Judd SE Kissela BM Lackland DT Lichtman JH Lisabeth LD Liu S Mackey RH Matchar DB McGuire DK Mohler ER Moy CS Muntner P Mussolino ME Nasir K Neumar RW Nichol G Palaniappan L Pandey DK Reeves MJ Rodriguez CJ Sorlie PD Stein J Towfighi A Turan TN Virani SS Willey JZ Woo D Yeh RW Turner MB American Heart Association Statistics Committee and Stroke Statistics Subcommittee 2015 Heart disease and stroke statistics--2015 update: a report from the American Heart Association Circulation 131 e13615 322 10.1161/CIR.0000000000000152 25520374 · DOI · Paper page
  30. Nature 2013 Reporting Checklist for Life Sciences Articles http://www.nature.com/authors/policies/checklist.pdf
  31. Nguyen DK Disteche CM 2006 Dosage compensation of the active X chromosome in mammals Nature Genetics 38 47 53 10.1038/ng1705 16341221 · DOI
  32. Ober C Loisel DA Gilad Y 2008 Sex-specific genetic architecture of human disease Nature Reviews Genetics 9 911 922 10.1038/nrg2415 PMC2694620 19002143 · DOI · Paper page
  33. Pennell LM Galligan CL Fish EN 2012 Sex affects immunity Journal of Autoimmunity 38 J282 291 10.1016/j.jaut.2011.11.013 22225601 · DOI
  34. Perrin S 2014 Preclinical research: Make mouse studies work Nature 507 423 425 10.1038/507423a 24678540 · DOI · Paper page
  35. Ross AP Mansilla MA Choe Y Helminski S Sturm R Maute RL May SR Wójcicki P Mostowska A Davidson B Adamopoulos IE Pleasure SJ Murray JC Zarbalis KS 2013 A mutation in mouse Pak1ip1 causes orofacial clefting while human PAK1IP1 maps to 6p24 translocation breaking points associated with orofacial clefting PLoS ONE 8 e13615 10.1371/journal.pone.0069333 PMC3723895 23935987 · DOI
  36. Settles B 2005 ABNER: an open source tool for automatically tagging genes, proteins and other entity names in text Bioinformatics 21 3191 3192 10.1093/bioinformatics/bti475 15860559 · DOI
  37. Taylor K Vallejo-Giraldo C Schaible NS Zakeri R Miller VM 2011 Reporting of sex as a variable in cardiovascular studies using cultured cells Biology of Sex Differences 2 e13615 10.1186/2042-6410-2-11 PMC3224776 22060014 · DOI
  38. van der Worp HB Howells DW Sena ES Porritt MJ Rewell S O'Collins V Macleod MR 2010 Can animal models of disease reliably inform human studies? PLoS Medicine 7 e13615 10.1371/journal.pmed.1000245 PMC2846855 20361020 · DOI · Paper page
  39. van der Worp HB Macleod MR 2011 Preclinical studies of human disease: time to take methodological quality seriously Journal of Molecular and Cellular Cardiology 51 449 450 10.1016/j.yjmcc.2011.04.008 21549125 · DOI
  40. Wizemann TM Pardue ML 2001 Exploring the Biological Contributions to Human Health: Does Sex Matter? Washington DC National Academy Press 25057540
  41. Yue F Cheng Y Breschi A Vierstra J Wu W Ryba T Sandstrom R Ma Z Davis C Pope BD Shen Y Pervouchine DD Djebali S Thurman RE Kaul R Rynes E Kirilusha A Marinov GK Williams BA Trout D Amrhein H Fisher-Aylor K Antoshechkin I DeSalvo G See LH Fastuca M Drenkow J Zaleski C Dobin A Prieto P Lagarde J Bussotti G Tanzer A Denas O Li K Bender MA Zhang M Byron R Groudine MT McCleary D Pham L Ye Z Kuan S Edsall L Wu YC Rasmussen MD Bansal MS Kellis M Keller CA Morrissey CS Mishra T Jain D Dogan N Harris RS Cayting P Kawli T Boyle AP Euskirchen G Kundaje A Lin S Lin Y Jansen C Malladi VS Cline MS Erickson DT Kirkup VM Learned K Sloan CA Rosenbloom KR Lacerda de Sousa B Beal K Pignatelli M Flicek P Lian J Kahveci T Lee D Kent WJ Ramalho Santos M Herrero J Notredame C Johnson A Vong S Lee K Bates D Neri F Diegel M Canfield T Sabo PJ Wilken MS Reh TA Giste E Shafer A Kutyavin T Haugen E Dunn D Reynolds AP Neph S Humbert R Hansen RS De Bruijn M Selleri L Rudensky A Josefowicz S Samstein R Eichler EE Orkin SH Levasseur D Papayannopoulou T Chang KH Skoultchi A Gosh S Disteche C Treuting P Wang Y Weiss MJ Blobel GA Cao X Zhong S Wang T Good PJ Lowdon RF Adams LB Zhou XQ Pazin MJ Feingold EA Wold B Taylor J Mortazavi A Weissman SM Stamatoyannopoulos JA Snyder MP Guigo R Gingeras TR Gilbert DM Hardison RC Beer MA Ren B Mouse ENCODE Consortium 2014 A comparative encyclopedia of DNA elements in the mouse genome Nature 515 355 364 10.1038/nature13992 25409824 PMC4266106 · DOI · Paper page

Authors
Flórez-Vargas, O., Brass, A., Karystianis, G., Bramhall, M., Stevens, R., Cruickshank, S., & Nenadic, G.
Affiliations
  • University of Manchester (GB)
  • Text Mining Group, School of Computer Science, The University of Manchester, Manchester, United Kingdom
Corresponding author
  • Flórez-Vargas, Oscar
  • Brass, Andy
Venue
eLife
Published
2016-03-03
Volume
5
ISSN
2050-084X (ISSN-L)
OpenAlex
W2291538400
Cited by
124
References
57
Citations by year
2026: 8 · 2025: 8 · 2024: 18 · 2023: 16 · 2022: 6 · 2021: 14 · 2020: 10 · 2019: 12 · 2018: 12 · 2017: 12 · 2016: 8
FWCI
14.54
Type
journal article
Language
en
Open access
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (acceptedVersion, other-oa)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Departamento Administrativo de Ciencia, Tecnología e Innovación (Scholarship)
  • Engineering and Physical Sciences Research Council (Scholarship)
  • Epistem Ltd (Scholarship)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › scientometrics and bibliometrics research
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
Keywords
sex bias, age reporting, mouse model, animal age, reporting quality, reproducibility, preclinical research, cardiovascular disease models, epidemic modeling
MeSH terms
Animals, Disease Models, Animal, Selection Bias, Age Distribution, Sex Distribution, Biomedical Research, Mice, Data Mining

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