title: Significant distinct branches of hierarchical trees: a framework for statistical analysis and applications to biological data.
abstract: BACKGROUND
  One of the most common goals of hierarchical clustering is finding those branches of a tree that form quantifiably distinct data subtypes. Achieving this goal in a statistically meaningful way requires (a) a measure of distinctness of a branch and (b) a test to determine the significance of the observed measure, applicable to all branches and across multiple scales of dissimilarity.
  
  
  RESULTS
  We formulate a method termed Tree Branches Evaluated Statistically for Tightness (TBEST) for identifying significantly distinct tree branches in hierarchical clusters. For each branch of the tree a measure of distinctness, or tightness, is defined as a rational function of heights, both of the branch and of its parent. A statistical procedure is then developed to determine the significance of the observed values of tightness. We test TBEST as a tool for tree-based data partitioning by applying it to five benchmark datasets, one of them synthetic and the other four each from a different area of biology. For each dataset there is a well-defined partition of the data into classes. In all test cases TBEST performs on par with or better than the existing techniques.
  
  
  CONCLUSIONS
  Based on our benchmark analysis, TBEST is a tool of choice for detection of significantly distinct branches in hierarchical trees grown from biological data. An R language implementation of the method is available from the Comprehensive R Archive Network: http://www.cran.r-project.org/web/packages/TBEST/index.html.
authors.forename: Guoli
authors.initials: G
authors.lastname: Sun
authors.affiliation: Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. krasnitz@cshl.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Krasnitz
mesh_terms: D002813:Chondrosarcoma / Q000235:genetics; D003198:Computer Simulation; D030541:Databases, Genetic; D008040:Genetic Linkage; D006801:Humans; D007938:Leukemia / Q000235:genetics; D015388:Organelles / Q000235:genetics; D010802:Phylogeny; D013223:Statistics as Topic; D013997:Time Factors