title: Topological characterization of neuronal arbor morphology via sequence representation: II--global alignment.
abstract: BACKGROUND
  The increasing abundance of neuromorphological data provides both the opportunity and the challenge to compare massive numbers of neurons from a wide diversity of sources efficiently and effectively. We implemented a modified global alignment algorithm representing axonal and dendritic bifurcations as strings of characters. Sequence alignment quantifies neuronal similarity by identifying branch-level correspondences between trees.
  
  
  RESULTS
  The space generated from pairwise similarities is capable of classifying neuronal arbor types as well as, or better than, traditional topological metrics. Unsupervised cluster analysis produces groups that significantly correspond with known cell classes for axons, dendrites, and pyramidal apical dendrites. Furthermore, the distinguishing consensus topology generated by multiple sequence alignment of a group of neurons reveals their shared branching blueprint. Interestingly, the axons of dendritic-targeting interneurons in the rodent cortex associates with pyramidal axons but apart from the (more topologically symmetric) axons of perisomatic-targeting interneurons.
  
  
  CONCLUSIONS
  Global pairwise and multiple sequence alignment of neurite topologies enables detailed comparison of neurites and identification of conserved topological features in alignment-defined clusters. The methods presented also provide a framework for incorporation of additional branch-level morphological features. Moreover, comparison of multiple alignment with motif analysis shows that the two techniques provide complementary information respectively revealing global and local features.
authors.affiliation: Department of Molecular Neuroscience, Center for Neural Informatics, Structures, and Plasticity, Krasnow Institute for Advanced Study (MS2A1), George Mason University, Fairfax, VA, USA. todd.gillette@gmail.com.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Gillette
authors.affiliation: Department of Molecular Neuroscience, Center for Neural Informatics, Structures, and Plasticity, Krasnow Institute for Advanced Study (MS2A1), George Mason University, Fairfax, VA, USA. phosseini13@gmail.com.
authors.forename: Parsa
authors.initials: P
authors.lastname: Hosseini
authors.affiliation: Department of Molecular Neuroscience, Center for Neural Informatics, Structures, and Plasticity, Krasnow Institute for Advanced Study (MS2A1), George Mason University, Fairfax, VA, USA. ascoli@gmu.edu.
authors.forename: Giorgio A
authors.initials: GA
authors.lastname: Ascoli
mesh_terms: D000465:Algorithms; D000818:Animals; D001369:Axons / Q000502:physiology*; D001483:Base Sequence; D003712:Dendrites / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid