title: Feature-guided clustering of multi-dimensional flow cytometry datasets.
abstract: BACKGROUND
  Flow cytometry produces large multi-dimensional datasets of the physical and molecular characteristics of individual cells. The objective of this study was to simplify the cytometry datasets by arranging or clustering "objects" (cells) into a smaller number of relatively homogeneous groups (clusters) on the basis of interobject similarities and dissimilarities.
  
  
  RESULTS
  The algorithm was designed to be driven by histogram features; that is, the relevant single parameter histogram features were used to guide multidimensional k-means clustering without an a priori estimate of cluster number. To test this approach, we simulated cell-derived datasets using protein-coated microspheres (artificial "cells"). The microspheres were constructed to provide 119 populations in 40 samples. The feature-guided (FG) approach accurately identified 100% of the predetermined cluster combinations. In contrast, an approach based on the partition index (PI) cluster validity measure accurately identified 83.2% of the clusters. Direct comparisons of the two methods indicated that the FG method was significantly more accurate than PI in identifying both the number of clusters and the number of objects within the clusters (p<.0001).
  
  
  CONCLUSIONS
  We conclude that parameter feature analysis can be used to effectively guide k-means clustering of flow cytometry datasets.
authors.affiliation: Decision Systems Group, Brigham and Women's Hospital, 310 Thorn Building, 75 Francis Street, Harvard Medical School, Boston, MA 02115, USA. qzeng@dsg.harvard.edu
authors.forename: Qing T
authors.initials: QT
authors.lastname: Zeng
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Pratt
authors.forename: Jane
authors.initials: J
authors.lastname: Pak
authors.forename: Dino
authors.initials: D
authors.lastname: Ravnic
authors.forename: Harold
authors.initials: H
authors.lastname: Huss
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mentzer
mesh_terms: D000465:Algorithms; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D001185:Artificial Intelligence; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D005434:Flow Cytometry / Q000379:methods*; D017143:Fuzzy Logic; D006801:Humans; D008863:Microspheres; D015233:Models, Statistical; D016571:Neural Networks, Computer; D010363:Pattern Recognition, Automated; D011381:Programming Languages; D012044:Regression Analysis
chemical_list: D000906:Antibodies