Integrating Statistical and Machine-Learning Approach for Meta-Analysis of Bisphenol A-Exposure Datasets Reveals Effects on Mouse Gene Expression within Pathways of Apoptosis and Cell Survival.

Journal: International journal of molecular sciences
PMID:

Abstract

Bisphenols are important environmental pollutants that are extensively studied due to different detrimental effects, while the molecular mechanisms behind these effects are less well understood. Like other environmental pollutants, bisphenols are being tested in various experimental models, creating large expression datasets found in open access storage. The meta-analysis of such datasets is, however, very complicated for various reasons. Here, we developed an integrating statistical and machine-learning model approach for the meta-analysis of bisphenol A (BPA) exposure datasets from different mouse tissues. We constructed three joint datasets following three different strategies for dataset integration: in particular, using all common genes from the datasets, uncorrelated, and not co-expressed genes, respectively. By applying machine learning methods to these datasets, we identified genes whose expression was significantly affected in all of the BPA microanalysis data tested; those involved in the regulation of cell survival include: , , , ; signaling through ()); DNA repair (, ); apoptosis (, , ); and cellular junctions (, , and ). Our results highlight the benefit of combining existing datasets for the integrated analysis of a specific topic when individual datasets are limited in size.

Authors

  • Nina Lukashina
    Machine Learning Applications and Deep Learning Group, JetBrains Research, Kantemirovskaya Str., 2, 197342 St. Petersburg, Russia.
  • Michael J Williams
    Department of Neuroscience, Functional Pharmacology, University of Uppsala, BMC, Husargatan 3, Box 593, 751 24 Uppsala, Sweden.
  • Elena Kartysheva
    Machine Learning Applications and Deep Learning Group, JetBrains Research, Kantemirovskaya Str., 2, 197342 St. Petersburg, Russia.
  • Elizaveta Virko
    Machine Learning Applications and Deep Learning Group, JetBrains Research, Kantemirovskaya Str., 2, 197342 St. Petersburg, Russia.
  • Błażej Kudłak
    Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza Str., 80-233 Gdańsk, Poland.
  • Robert Fredriksson
    Department of Pharmaceutical Biosciences, Molecular Neuropharmacology, Uppsala Biomedical Centre, University of Uppsala, Husargatan 3, Box 591, 751 24 Uppsala, Sweden.
  • Ola Spjuth
    Department of Pharmaceutical Biosciences , Uppsala University , Box 591, SE-75124 , Uppsala Sweden.
  • Helgi B Schiöth
    Department of Surgical Sciences, Functional Pharmacology and Neuroscience, Uppsala University, Uppsala, Sweden.