title: Machine vision-assisted analysis of structure-localization relationships in a combinatorial library of prospective bioimaging probes.
abstract: With a combinatorial library of bioimaging probes, it is now possible to use machine vision to analyze the contribution of different building blocks of the molecules to their cell-associated visual signals. For this purpose, cell-permeant, fluorescent styryl molecules were synthesized by condensation of 168 aldehyde with 8 pyridinium/quinolinium building blocks. Images of cells incubated with fluorescent molecules were acquired with a high content screening instrument. Chemical and image feature analysis revealed how variation in one or the other building block of the styryl molecules led to variations in the molecules' visual signals. Across each pair of probes in the library, chemical similarity was significantly associated with spectral and total signal intensity similarity. However, chemical similarity was much less associated with similarity in subcellular probe fluorescence patterns. Quantitative analysis and visual inspection of pairs of images acquired from pairs of styryl isomers confirm that many closely-related probes exhibit different subcellular localization patterns. Therefore, idiosyncratic interactions between styryl molecules and specific cellular components greatly contribute to the subcellular distribution of the styryl probes' fluorescence signal. These results demonstrate how machine vision and cheminformatics can be combined to analyze the targeting properties of bioimaging probes, using large image data sets acquired with automated screening systems.
authors.affiliation: Department of Statistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Kerby
authors.initials: K
authors.lastname: Shedden
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Fangyi
authors.initials: F
authors.lastname: Liu
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Chang
authors.forename: Gus R
authors.initials: GR
authors.lastname: Rosania
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000465:Algorithms; D020650:Combinatorial Chemistry Techniques; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000302:isolation & purification; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D000447:Aldehydes; D005456:Fluorescent Dyes