Application of neural networks to flow cytometry data analysis and real-time cell classification.

Conventional analysis of flow cytometric data requires that population identification be performed graphically after a sample has been run using two-parameter scatter plots. As more parameters are measured, the number of possible two-parameter plots increases geometrically, making data analysis increasingly cumbersome. Artificial Neural Systems (ANS), also known as neural networks, are a powerful and convenient method for overcoming this data bottleneck. ANS "learn" to make classifications using all of the measured parameters simultaneously. Mathematical models and programming expertise are not required. ANS are inherently parallel so that high processing speed can be achieved. Because ANS are nonlinear, curved class boundaries and other nonlinearities can emerge naturally. Here, we present biomedical and oceanographic data to demonstrate the useful properties of neural networks for processing and analyzing flow cytometry data. We show that ANS are equally useful for human leukocytes and marine plankton data. They can easily accommodate nonlinear variations in data, detect subtle changes in measurements, interpolate and classify cells they were not trained on, and analyze multiparameter cell data in real time. Real-time classification of a mixture of six cyanobacteria strains was achieved with an average accuracy of 98%.

[1]  J. Waterbury,et al.  Biological and ecological characterization of the marine unicellular Cyanobacterium Synechococcus , 1987 .

[2]  P. G. N. Digby,et al.  Multivariate Analysis of Ecological Communities , 1987 .

[3]  M. Goldstein,et al.  Multivariate Analysis: Methods and Applications , 1984 .

[4]  H. W. Balfoort,et al.  Automatic identification of algae: neural network analysis of flow cytometric data , 1992 .

[5]  D R Parks,et al.  Pattern sorting: a computer-controlled multidimensional sorting method using k-d trees. , 1994, Cytometry.

[6]  Sallie W. Chisholm,et al.  Use of a neural net computer system for analysis of flow cytometric data of phytoplankton populations , 1989 .

[7]  Peter H. A. Sneath,et al.  Numerical Taxonomy: The Principles and Practice of Numerical Classification , 1973 .

[8]  Sallie W. Chisholm,et al.  High‐sensitivity flow cytometer for studying picoplankton , 1990 .

[9]  James L. McClelland,et al.  Parallel distributed processing: explorations in the microstructure of cognition, vol. 1: foundations , 1986 .

[10]  P M Ravdin,et al.  Neural Network Analysis of DNA flow cytometry histograms. , 1993, Cytometry.

[11]  L O Henderson,et al.  Model system evaluating fluorescein-labeled microbeads as internal standards to calibrate fluorescence intensity on flow cytometers. , 1989, Cytometry.

[12]  Sallie W. Chisholm,et al.  A novel free-living prochlorophyte abundant in the oceanic euphotic zone , 1988, Nature.

[13]  C. W. Morris,et al.  Neural network analysis of flow cytometric data for 40 marine phytoplankton species. , 1994, Cytometry.

[14]  William K. W. Li Bivariate and trivariate analysis in flow cytometry: Phytoplankton size and fluorescence , 1990 .

[15]  M R Loken,et al.  Discriminating between damaged and intact cells in fixed flow cytometric samples. , 1988, Cytometry.

[16]  S Demers,et al.  Analyzing multivariate flow cytometric data in aquatic sciences. , 1992, Cytometry.

[17]  Sallie W. Chisholm,et al.  Marine phytoplankton distributions measured using shipboard flow cytometry , 1985 .

[18]  T C Bakker Schut,et al.  Cluster analysis of flow cytometric list mode data on a personal computer. , 1993, Cytometry.

[19]  Sallie W. Chisholm,et al.  Advances in Oceanography through Flow Cytometry , 1991 .

[20]  A Schwartz,et al.  Development of Clinical Standards for Flow Cytometry , 1993, Annals of the New York Academy of Sciences.

[21]  P A Errington,et al.  Application of artificial neural networks to chromosome classification. , 1993, Cytometry.

[22]  Richard J. Beckman,et al.  AutoGate: A Macintosh cluster analysis program for flow cytometry data , 1993 .