title: Stronger findings for metabolomics through Bayesian modeling of multiple peaks and compound correlations.
abstract: BACKGROUND
  Data analysis for metabolomics suffers from uncertainty because of the noisy measurement technology and the small sample size of experiments. Noise and the small sample size lead to a high probability of false findings. Further, individual compounds have natural variation between samples, which in many cases renders them unreliable as biomarkers. However, the levels of similar compounds are typically highly correlated, which is a phenomenon that we model in this work.
  
  
  RESULTS
  We propose a hierarchical Bayesian model for inferring differences between groups of samples more accurately in metabolomic studies, where the observed compounds are collinear. We discover that the method decreases the error of weak and non-existent covariate effects, and thereby reduces false-positive findings. To achieve this, the method makes use of the mass spectral peak data by clustering similar peaks into latent compounds, and by further clustering latent compounds into groups that respond in a coherent way to the experimental covariates. We demonstrate the method with three simulated studies and validate it with a metabolomic benchmark dataset.
  
  
  METHODS
  An implementation in R is available at http://research.ics.aalto.fi/mi/software/peakANOVA/.
authors.affiliation: Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, FI-00076 Espoo, Finland, School of Computing Science, University of Glasgow, Glasgow G12 8QQ, UK and Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki, Finland.
authors.forename: Tommi
authors.initials: T
authors.lastname: Suvitaival
authors.affiliation: Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, FI-00076 Espoo, Finland, School of Computing Science, University of Glasgow, Glasgow G12 8QQ, UK and Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki, Finland.
authors.forename: Simon
authors.initials: S
authors.lastname: Rogers
authors.affiliation: Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, FI-00076 Espoo, Finland, School of Computing Science, University of Glasgow, Glasgow G12 8QQ, UK and Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki, Finland Helsinki Institute for Information Technology HIIT, Department of Information and Computer Science, Aalto University, FI-00076 Espoo, Finland, School of Computing Science, University of Glasgow, Glasgow G12 8QQ, UK and Helsinki Institute for Information Technology HIIT, Department of Computer Science, University of Helsinki, Helsinki, Finland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kaski
mesh_terms: D001499:Bayes Theorem; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D018401:Sample Size