title: Feature-expression heat maps--a new visual method to explore complex associations between two variable sets.
abstract: BACKGROUND
  Existing methods such as correlation plots and cluster heat maps are insufficient in the visual exploration of multiple associations between genetics and phenotype, which is of importance to achieve a better understanding of the pathophysiology of psychiatric and other illnesses. The implementation of a combined presentation of effect size and statistical significance in a graphical method, added to the ordering of the variables based on the effect-ordered data display principle was deemed useful by the authors to facilitate in the process of recognizing meaningful patterns in these associations.
  
  
  METHODS
  The requirements, analyses and graphical presentation of the feature-expression heat map are described. The graphs display associations of two sets of ordered variables where a one-way direction is assumed. The associations are depicted as circles representing a combination of effect size (color) and statistical significance (radius).
  
  
  RESULTS
  An example dataset is presented and relation to other methods, limitations, areas of application and possible future enhancements are discussed.
  
  
  CONCLUSIONS
  The feature-expression heat map is a useful graphical instrument to explore associations in complex biological systems where one-way direction is assumed, such as genotype-phenotype pathophysiological models.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands. Electronic address: b.c.m.haarman@umcg.nl.
authors.forename: Bartholomeus C M Benno
authors.initials: BC
authors.lastname: Haarman
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands. Electronic address: r.f.riemersma@umcg.nl.
authors.forename: Rixt F
authors.initials: RF
authors.lastname: Riemersma-Van der Lek
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands. Electronic address: w.a.nolen@umcg.nl.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.affiliation: Health E-Solutions, Rotterdam, The Netherlands. Electronic address: r.mendes@healthesolutions.nl.
authors.forename: R
authors.initials: R
authors.lastname: Mendes
authors.affiliation: Erasmus MC, Rotterdam, Department of Immunology, The Netherlands. Electronic address: h.drexhage@erasmusmc.nl.
authors.forename: Hemmo A
authors.initials: HA
authors.lastname: Drexhage
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen, The Netherlands. Electronic address: h.burger@umcg.nl.
authors.forename: Huibert
authors.initials: H
authors.lastname: Burger
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D003116:Color; D019295:Computational Biology / Q000379:methods*; D003196:Computer Graphics; D003625:Data Collection; D003626:Data Display; D005189:False Positive Reactions; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D005838:Genotype; D006358:Hot Temperature; D006801:Humans; D008957:Models, Genetic; D009000:Monocytes / Q000166:cytology; D010641:Phenotype; D012044:Regression Analysis
keywords: Associations; Genotype; Graph; Heat map; Method; Phenotype