MedicalResearch.com Interview with:
Dr Mandy Peffers BSc MPhil PhD BVetMed FRCVS
Wellcome Trust Clinical Intermediate Fellow
Institute of Ageing & Chronic Disease
Faculty of Health & Life Sciences
University of Liverpool Liverpool UK
MedicalResearch.com: What is the background for this study?
Response: The project was an extension of Louise Pease’s MSc research project in bioinformatics which aimed to re-analyse existing RNA-seq data to determine age related changes in gene expression in musculoskeletal tissues that may lead to the development of degenerative diseases. From existing literature we identified that degenerative diseases such as osteoarthritis and tendinitis were more prevalent in females and became more frequent following menopause. We looked at the biology of the cohort we were trying to assess and discovered a gender imbalance, we hypothesised that this was why few results had been obtained from the original analysis. So we developed a research proposal that detailed extending the existing data to publicly available data and merging the experiments; to increase the number of replicates available and balance the experimental design. We conducted multiple analyses and discovered that splitting samples by age and gender obtained the most significant results, and that whilst in a lot of cases the same genes were being differentially expressed, they were changing in opposite directions. Louise remembered her statistics lecturer Gerard Cowburn (Ged) taught her about the assumptions of statistical tests, in particular covariance analysis (which has previously been used to show that age and gender do not affect gene expression) assumed that under the conditions being tested data points were not opposites. Realising that this assumption had been violated by the data she began to think about what other assumptions we were working with and how to test their validity.