iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://unpaywall.org/10.1007/S12021-018-9399-4
Automated Neuron Detection in High-Content Fluorescence Microscopy Images Using Machine Learning | Neuroinformatics Skip to main content

Advertisement

Log in

Automated Neuron Detection in High-Content Fluorescence Microscopy Images Using Machine Learning

  • Original Article
  • Published:
Neuroinformatics Aims and scope Submit manuscript

Abstract

The study of neuronal morphology in relation to function, and the development of effective medicines to positively impact this relationship in patients suffering from neurodegenerative diseases, increasingly involves image-based high-content screening and analysis. The first critical step toward fully automated high-content image analyses in such studies is to detect all neuronal cells and distinguish them from possible non-neuronal cells or artifacts in the images. Here we investigate the performance of well-established machine learning techniques for this purpose. These include support vector machines, random forests, k-nearest neighbors, and generalized linear model classifiers, operating on an extensive set of image features extracted using the compound hierarchy of algorithms representing morphology, and the scale-invariant feature transform. We present experiments on a dataset of rat hippocampal neurons from our own studies to find the most suitable classifier(s) and subset(s) of features in the common practical setting where there is very limited annotated data for training. The results indicate that a random forests classifier using the right feature subset ranks best for the considered task, although its performance is not statistically significantly better than some support vector machine based classification models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  • Anderl, J.L., Redpath, S., Ball, A.J. (2009). A neuronal and astrocyte co-culture assay for high content analysis of neurotoxicity. Journal of Visualized Experiments, 5(27), 1173.

    Google Scholar 

  • Antony, P.M.A., Trefois, C., Stojanovic, A., Baumuratov, A.S., Kozak, K. (2013). Light microscopy applications in systems biology: opportunities and challenges. Cell Communication and Signaling, 11(24), 1–19.

    Google Scholar 

  • Arganda-Carreras, I., Kaynig, V., Rueden, C., Eliceiri, K.W., Schindelin, J., Cardona, A., Seung, H.S. (2017). Trainable Weka Segmentation: a machine learning tool for microscopy pixel classification. Bioinformatics, 33(15), 2424–2426.

    Article  CAS  PubMed  Google Scholar 

  • Ascoli, G.A. (2015). Trees of the brain, roots of the mind. Cambridge: MIT Press.

    Book  Google Scholar 

  • Bianchini, M., & Scarselli, F. (2014). On the complexity of neural network classifiers: a comparison between shallow and deep architectures. IEEE Transactions on Neural Networks and Learning Systems, 25(8), 1553–1565.

    Article  PubMed  Google Scholar 

  • Bischl, B., Mersmann, O., Trautmann, H., Weihs, C. (2012). Resampling methods for meta-model validation with recommendations for evolutionary computation. Evolutionary Computation, 20(2), 249–275.

    Article  CAS  PubMed  Google Scholar 

  • Bischl, B., Lang, M., Kotthoff, L., Schiffner, J., Richter, J., Jones, Z., Casalicchio, G. (2016). mlr: Machine Learning in R. https://CRAN.R-project.org/package=mlr.

  • Bishop, C.M. (2006). Pattern recognition and machine learning. New York: Springer.

    Google Scholar 

  • Boser, B.E., Guyon, I.M., Vapnik, V.N. (1992). A training algorithm for optimal margin classifiers. In Proceedings of the 5th Annual ACM Workshop on Computational Learning Theory (pp. 144–152).

  • Bougen-Zhukov, N., Loh, S.Y., Lee, H.K., Loo, L.H. (2017). Large-scale image-based screening and profiling of cellular phenotypes. Cytometry Part A, 91(2), 115–125.

    Article  Google Scholar 

  • Branco, P., Torgo, L., Ribeiro, R.P. (2016). A survey of predictive modeling on imbalanced domains. ACM Computing Surveys, 49(2), 31:1–31:50.

    Article  Google Scholar 

  • Bredenbeek, P.J., Frolov, I., Rice, C.M., Schlesinger, S. (1993). Sindbis virus expression vectors: packaging of RNA, replicons by using defective helper RNAs. Journal of Virology, 67(11), 6439–6446.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Breiman, L. (2001). Random forests. Machine Learning, 45(1), 5–32.

    Article  Google Scholar 

  • Burges, C.J.C. (1998). A tutorial on support vector machines for pattern recognition. Data Mining and Knowledge Discovery, 2(2), 121–167.

    Article  Google Scholar 

  • Charoenkwan, P., Hwang, E., Cutler, R.W., Lee, H.C., Ko, L.W., Huang, H.L., Ho, S.Y. (2013). HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening. BMC Bioinformatics, 14(S16), S12.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chawla, N.V., Bowyer, K.W., Hall, L.O., Kegelmeyer, W.P. (2002). SMOTE: Synthetic minority over-sampling technique. Journal of Artificial Intelligence Research, 16(1), 321–357.

    Article  Google Scholar 

  • Chawla, N.V., Japkowicz, N., Kotcz, A. (2004). Editorial: Special issue on learning from imbalanced data sets. ACM SIGKDD Explorations Newsletter, 6(1), 1–6.

    Article  Google Scholar 

  • Cover, T., & Hart, P. (1967). Nearest neighbor pattern classification. IEEE Transactions on Information Theory, 13(1), 21–27.

    Article  Google Scholar 

  • Cristianini, N., & Shawe-Taylor, J. (2000). An introduction to support vector machines and other Kernel-Based learning methods. Cambridge: University Press.

    Book  Google Scholar 

  • Cuesto, G., Enriquez-Barreto, L., Caramés, C., Cantarero, M., Gasull, X., Sandi, C., Ferrús, A., Acebes, Á., Morales, M. (2011). Phosphoinositide-3-kinase activation controls synaptogenesis and spinogenesis in hippocampal neurons. Journal of Neuroscience, 31(8), 2721–2733.

    Article  CAS  PubMed  Google Scholar 

  • Dalal, N., & Triggs, B. (2005). Histograms of oriented gradients for human detection. In Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition (pp. 886–893).

  • Daskalaki, S., Kopanas, I., Avouris, N. (2006). Evaluation of classifiers for an uneven class distribution problem. Applied Artificial Intelligence, 20(5), 381–417.

    Article  Google Scholar 

  • Dehmelt, L., Poplawski, G., Hwang, E., Halpain, S. (2011). NeuriteQuant: an open source toolkit for high content screens of neuronal morphogenesis. BMC Neuroscience, 12(100), 1–13.

    Google Scholar 

  • Dragunow, M. (2008). High-content analysis in neuroscience. Nature Reviews Neuroscience, 9(10), 779–788.

    Article  CAS  PubMed  Google Scholar 

  • Ebrahimpour, M.K., Zare, M., Eftekhari, M., Aghamolaei, G. (2017). Occam’s razor in dimension reduction: using reduced row Echelon, form for finding linear independent features in high dimensional microarray datasets. Engineering Applications of Artificial Intelligence, 62, 214–221.

    Article  Google Scholar 

  • Enriquez-Barreto, L., Cuesto, G., Dominguez-Iturza, N., Gavilán, E., Ruano, D., Sandi, C., Fernández-Ruiz, A., Martín-Vázquez, G., Herreras, O., Morales, M. (2014). Learning improvement after PI3K, activation correlates with de novo formation of functional small spines. Frontiers in Molecular Neuroscience, 6, 54.

    Article  PubMed  PubMed Central  Google Scholar 

  • Enriquez-Barreto, L., & Morales, M. (2016). The PI3K, signaling pathway as a pharmacological target in autism related disorders and schizophrenia. Molecular and Cellular Therapies, 4, 2.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fawcett, T. (2006). An introduction to ROC, analysis. Pattern Recognition Letters, 27(8), 861–874.

    Article  Google Scholar 

  • Fei-Fei, L., & Perona, P. (2005). A Bayesian hierarchical model for learning natural scene categories. In Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, (Vol. 2 pp. 524–531).

  • Fernandez-Lozano, C., Gestal, M., Munteanu, C.R., Dorado, J., Pazos, A. (2016). A methodology for the design of experiments in computational intelligence with multiple regression models. PeerJ, 4, e2721.

    Article  PubMed  PubMed Central  Google Scholar 

  • Finner, H. (1993). On a monotonicity problem in step-down multiple test procedures. Journal of the American Statistical Association, 88(423), 920–923.

    Article  Google Scholar 

  • Forman, G., & Scholz, M. (2010). Apples-to-apples in cross-validation studies: pitfalls in classifier performance measurement. ACM SIGKDD Explorations Newsletter, 12(1), 49–57.

    Article  Google Scholar 

  • Friedman, M. (1940). A comparison of alternative tests of significance for the problem of m rankings. Annals of Mathematical Statistics, 11(1), 86–92.

    Article  Google Scholar 

  • Friedman, J., Hastie, T., Tibshirani, R. (2010). Regularization paths for generalized linear models via coordinate descent. Journal of Statistical Software, 33(1), 1–22.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gabor, D. (1946). Theory of communication. Journal of the Institution of Electrical Engineers — Part III: Radio and Communication Engineering, 93(26), 429–457.

    Google Scholar 

  • García, S., Fernández, A., Luengo, J., Herrera, F. (2010). Advanced nonparametric tests for multiple comparisons in the design of experiments in computational intelligence and data mining: experimental analysis of power. Information Sciences, 180(10), 2044–2064.

    Article  Google Scholar 

  • García, V., Mollineda, R.A., Sȧnchez, J.S. (2014). A bias correction function for classification performance assessment in two-class imbalanced problems. Knowledge-Based Systems, 59, 66–74.

    Article  Google Scholar 

  • Ghosh, A., Kumar, H., Sastry, P.S. (2017). Robust loss functions under label noise for deep neural networks. In Proceedings of the AAAI Conference on Artificial Intelligence (pp. 1919–1925).

  • Goslin, K., Asumussen, H., Banker, G. (1998). Rat hippocampal neurons in low-density culture. In Culturing Nerve cells (pp. 339–370). Cambridge: The MIT Press.

  • Gosain, A., & Sardana, S. (2017). Handling class imbalance problem using oversampling techniques: a review, In Proceedings of the International Conference on Advances in Computing, Communications and Informatics (pp. 79–85).

  • Gradshteyn, I.S., & Ryzhik, I.M. (1994). Table of integrals, series and products. New York: Academic Press.

    Google Scholar 

  • Greenspan, H., van Ginneken, B., Summers, R.M. (2016). Deep learning in medical imaging: overview and future promise of an exciting new technique. IEEE Transactions on Medical Imaging, 35(5), 1153–1159.

    Article  Google Scholar 

  • Gupta, P., Batra, S.S., Jayadeva. (2017). Sparse short-term time series forecasting models via minimum model complexity. Neurocomputing, 243, 1–11.

    Article  Google Scholar 

  • Hadjidementriou, E., Grossberg, M., Nayar, S. (2001). Spatial information in multiresolution histograms. In Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (pp. I.702–I.709).

  • Haixiang, G., Yijing, L., Shang, J., Mingyun, G., Yuanyue, H., Bing, G. (2017). Learning from class-imbalanced data: review of methods and applications. Expert Systems with Applications, 73, 220–239.

    Article  Google Scholar 

  • Haralick, R.M., Shanmugam, K., Dinstein, I. (1973). Textural features for image classification. IEEE Transactions on Systems, Man, and Cybernetics, 3(6), 610–621.

    Article  Google Scholar 

  • He, H., & Garcia, E.A. (2009). Learning from imbalanced data. IEEE Transactions on Knowledge and Data Engineering, 21(9), 1263–1284.

    Article  Google Scholar 

  • He, K., Zhang, X., Ren, S., Sun, J. (2016). Deep residual learning for image recognition. In Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (pp. 770–778).

  • Hechenbichler, K., & Schliep, K. (2004). Weighted k-nearest-neighbor techniques and ordinal classification. Sonderforschungsbereich, 386(399), 1–16.

    Google Scholar 

  • Hong, X., Gao, J., Chen, S., Harris, C.J. (2013). Particle swarm optimisation assisted classification using elastic net prefiltering. Neurocomputing, 122, 210–220.

    Article  Google Scholar 

  • Horvath, P., Wild, T., Kutay, U., Csucs, G. (2011). Machine learning improves the precision and robustness of high-content screens: using nonlinear multiparametric methods to analyze screening results. Journal of Biomolecular Screening, 16(9), 1059–1067.

    Article  CAS  PubMed  Google Scholar 

  • Iacca, G., Neri, F., Mininno, E., Ong, Y.S., Lim, M.H. (2012). Ockham’s razor in memetic computing: three stage optimal memetic exploration. Information Sciences, 188, 17–43.

    Article  Google Scholar 

  • Jain, S., van Kesteren, R.E., Heutink, P. (2012). High content screening in neurodegenerative diseases. Journal of Visualized Experiments, 59, e3452.

    Google Scholar 

  • Jiang, R.M., Crookes, D., Luo, N., Davidson, M.W. (2010). Live-cell tracking using SIFT, features in DIC microscopic videos. IEEE Transactions on Biomedical Engineering, 57(9), 2219–2228.

    Article  PubMed  Google Scholar 

  • Kingma, D.P., & Ba, J. (2014). Adam: a method for stochastic optimization, Computing Research Repository arXiv:1412.6980.

  • Kraus, O.Z., & Frey, B.J. (2016). Computer vision for high content screening. Critical Reviews in Biochemistry and Molecular Biology, 51(2), 102–109.

    Article  PubMed  Google Scholar 

  • Krawczyk, B. (2016). Learning from imbalanced data: open challenges and future directions. Progress in Artificial Intelligence, 5(4), 221–232.

    Article  Google Scholar 

  • Kuminski, E., George, J., Wallin, J., Shamir, L. (2014). Combining human and machine learning for morphological analysis of galaxy images. Publications of the Astronomical Society of the Pacific, 126(944), 959–967.

    Article  Google Scholar 

  • Lazebnik, S., Schmid, C., Ponce, J. (2006). Beyond bags of features: Spatial pyramid matching for recognizing natural scene categories. In Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, (Vol. 2 pp. 2169–2178).

  • LeCun, Y., Bengio, Y., Hinton, G. (2015). Deep learning. Nature, 521(7553), 436–444.

    Article  CAS  PubMed  Google Scholar 

  • Lee, D.H., Lee, D.W., Han, B.S. (2016). Possibility study of scale invariant feature transform (SIFT), algorithm application to spine magnetic resonance imaging. PLOS ONE, 11(4), 1–9.

    Google Scholar 

  • Li, J., Fong, S., Wong, R.K., Chu, V.W. (2018). Adaptive multi-objective swarm fusion for imbalanced data classification. Information Fusion, 39, 1–24.

    Article  Google Scholar 

  • Liaw, A., & Wiener, M. (2002). Classification and regression by randomForest. R News, 2(3), 18–22.

    Google Scholar 

  • Litjens, G., Kooi, T., Bejnordi, B.E., Setio, A.A.A., Ciompi, F., Ghafoorian, M., van der Laak, J.A.W.M., van Ginneken, B., Sánchez, C.I. (2017). A survey on deep learning in medical image analysis. Medical Image Analysis, 42, 60–88.

    Article  PubMed  Google Scholar 

  • Lowe, D.G. (2004). Distinctive image features from scale-invariant keypoints. International Journal of Computer Vision, 60(2), 91–110.

    Article  Google Scholar 

  • MacQueen, J. (1967). Some methods for classification and analysis of multivariate observations. In Proceedings of the 5th Berkeley Symposium on Mathematical Statistics and Probability — Volume 1: Statistics (pp. 281–297). Berkeley: University of California Press.

  • Mata, G., Radojević, M., Smal, I., Morales, M., Meijering, E., Rubio, J. (2016). Automatic detection of neurons in high-content microscope images using machine learning approaches. In Proceedings of the IEEE International Symposium on Biomedical Imaging: From Nano to Macro (pp. 330–333).

  • MathWorks. (2016). Version 9.0.0.341360 (R2016a). Natick: MA.

    Google Scholar 

  • Meijering, E. (2010). Neuron tracing in perspective. Cytometry Part A, 77(7), 693–704.

    Article  Google Scholar 

  • Meijering, E., Carpenter, A.E., Peng, H., Hamprecht, F.A., Olivo-Marin, J.C. (2016). Imagining the future of bioimage analysis. Nature Biotechnology, 34(12), 1250–1255.

    Article  CAS  PubMed  Google Scholar 

  • Meyer, D., Dimitriadou, E., Hornik, K., Weingessel, A., Leisch, F. (2017). e1071: Misc Functions of the Department of Statistics, Probability Theory Group (Formerly: E1071), TU Wien. https://CRAN.R-project.org/package=e1071.

  • Mualla, F., Scholl, S., Sommerfeldt, B., Maier, A., Hornegger, J. (2013). Automatic cell detection in bright-field microscope images using SIFT, random forests, and hierarchical clustering. IEEE Transactions on Medical Imaging, 32(12), 2274–2286.

    Article  PubMed  Google Scholar 

  • Ni, D., Chui, Y.P., Qu, Y., Yang, X.S., Qin, J., Wong, T.T., Ho, S.S.H., Heng, P.A. (2009). Reconstruction of volumetric ultrasound panorama based on improved 3D, SIFT. Computerized Medical Imaging and Graphics, 33(7), 559–566.

    Article  PubMed  Google Scholar 

  • Orlov, N., Shamir, L., Macura, T., Johnston, J., Eckley, D.M., Goldberg, I.G. (2008). WND-CHARM: Multi-purpose image classification using compound image transforms. Pattern Recognition Letters, 29(11), 1684–1693.

    Article  PubMed  PubMed Central  Google Scholar 

  • Otsu, N. (1979). A threshold selection method from gray-level histograms. IEEE Transactions on Systems, Man, and Cybernetics, 9(1), 62–66.

    Article  Google Scholar 

  • van Pelt, J., van Ooyen, A., Uylings, H. (2001). The need for integrating neuronal morphology databases and computational environments in exploring neuronal structure and function. Anatomy and Embryology, 204(4), 255–265.

    Article  PubMed  Google Scholar 

  • Prewitt, J.M.S. (1970). Object enhancement and extraction. In Picture Processing and psychopictorics (pp. 75–149). New York: Academic Press.

  • R Core Team. (2016). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria, https://www.R-project.org/.

  • Radio, N. (2012). Neurite outgrowth assessment using high content analysis methodology. Methods in Molecular Biology, 846, 247–260.

    Article  CAS  PubMed  Google Scholar 

  • Ramón y Cajal, S. (2007). Histología del sistema nervioso del hombre y de los vertebrados. CSIC Madrid reprinted in.

  • Saeys, Y., Inza, I., Larrañaga, P. (2007). A review of feature selection techniques in bioinformatics. Bioinformatics, 23(19), 2507–2517.

    Article  CAS  PubMed  Google Scholar 

  • Sáez, J.A., Luengo, J., Stefanowski, J., Herrera, F. (2015). SMOTE-IPF: Addressing the noisy and borderline examples problem in imbalanced classification by a re-sampling method with filtering. Information Sciences, 291, 184–203.

    Article  Google Scholar 

  • Samworth, R.J. (2012). Optimal weighted nearest neighbour classifiers. The Annals of Statistics, 40(5), 2733–2763.

    Article  Google Scholar 

  • Schliep, K., & Hechenbichler, K. (2016). kknn: Weighted k-Nearest Neighbors. https://CRAN.R-project.org/package=kknn.

  • Shaikhina, T., & Khovanova, N.A. (2017). Handling limited datasets with neural networks in medical applications: a small-data approach. Artificial Intelligence in Medicine, 75, 51–63.

    Article  PubMed  Google Scholar 

  • Shamir, L., Orlov, N., Eckley, D.M., Macura, T., Johnston, J., Goldberg, I.G. (2008). Wndchrm – an open source utility for biological image analysis. Source Code for Biology and Medicine, 3(1), 1–13.

    Article  Google Scholar 

  • Shamir, L., Delaney, J.D., Orlov, N., Eckley, D.M., Goldberg, I.G. (2010). Pattern recognition software and techniques for biological image analysis. PLOS Computational Biology, 6(11), e1000974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shamir, L. (2012a). Automatic detection of peculiar galaxies in large datasets of galaxy images. Journal of Computational Science, 3(3), 181–189.

    Article  Google Scholar 

  • Shamir, L., & Tarakhovsky, J.A. (2012b). Computer analysis of art. Journal on Computing and Cultural Heritage, 5(2), 7.

    Article  Google Scholar 

  • Shapiro, S.S., & Wilk, M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika, 52(3-4), 591– 611.

    Article  Google Scholar 

  • Shen, D., Wu, G., Suk, H.I. (2017). Deep learning in medical image analysis. Annual Review of Biomedical Engineering, 19, 221– 248.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simon, R. (2007). Resampling strategies for model assessment and selection. In Fundamentals of Data Mining in Genomics and Proteomics (pp. 173–186). Boston: Springer.

  • Simonyan, K., & Zisserman, A. (2014). Very deep convolutional networks for large-scale image recognition. Computing Research Repository arXiv:1409.1556.

  • Singh, S., Carpenter, A.E., Genovesio, A. (2014). Increasing the content of high-content screening: an overview. Journal of Biomolecular Screening, 19(5), 640–650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smafield, T., Pasupuleti, V., Sharma, K., Huganir, R.L., Ye, B., Zhou, J. (2015). Automatic dendritic length quantification for high throughput screening of mature neurons. Neuroinformatics, 13(4), 443–458.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sommer, C., & Gerlich, D.W. (2013). Machine learning in cell biology – teaching computers to recognize phenotypes. Journal of Cell Science, 126(24), 5529–5539.

    Article  CAS  PubMed  Google Scholar 

  • Squire, L.R. (1992). Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychological Review, 99(2), 195–231.

    Article  CAS  Google Scholar 

  • Strobl, C., Hothorn, T., Zeileis, A. (2009). A new, conditional variable importance measure for random forests available in the party package. The R Journal, 1(2), 14–17.

    Article  Google Scholar 

  • Tajbakhsh, N., Shin, J.Y., Gurudu, S.R., Hurst, R.T., Kendall, C.B., Gotway, M.B., Liang, J. (2016). Convolutional neural networks for medical image analysis: full training or fine tuning?. IEEE Transactions on Medical Imaging, 35(5), 1299–1312.

    Article  PubMed  Google Scholar 

  • Tamura, H., Mori, S., Yamawaki, T. (1978). Textural features corresponding to visual perception. IEEE Transactions on Systems Man, and Cybernetics, 8(6), 460–473.

    Article  Google Scholar 

  • Tibshirani, R. (1996). Regression shrinkage and selection via the lasso. Journal of the Royal Statistical Society: Series B (Statistical Methodology), 58(1), 267–288.

    Google Scholar 

  • Uhlmann, V., Singh, S., Carpenter, A.E. (2016). CP-CHARM: segmentation-free image classification made accessible. BMC Bioinformatics, 17(1), 51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vallotton, P., Lagerstrom, R., Sun, C., Buckley, M., Wang, D., Silva, M.D., Tan, S.S., Gunnersen, J.M. (2007). Automated analysis of neurite branching in cultured cortical neurons using HCA-Vision. Cytometry Part A, 71(10), 889–895.

    Article  Google Scholar 

  • Vapnik, V.N. (1998). Statistical learning theory. New York: Wiley.

    Google Scholar 

  • Vapnik, V.N. (1999). The nature of statistical learning theory. New York: Springer-Verlag.

    Google Scholar 

  • Vedaldi, A., & Fulkerson, B. (2008). VLFeat: An Open and Portable Library of Computer Vision Algorithms. http://www.vlfeat.org/.

  • Vert, J.P., Tsuda, K., Schölkopf, B. (2004). A primer on kernel methods. In Kernel Methods in Computational Biology (pp. 35–70). Cambridge: MIT Press.

  • Wickham, H. (2009). Ggplot2: Elegant Graphics for Data Analysis. New York: Springer.

    Book  Google Scholar 

  • Wu, C., Schulte, J., Sepp, K.J., Littleton, J.T., Hong, P. (2010). Automatic robust neurite detection and morphological analysis of neuronal cell cultures in high-content screening. Neuroinformatics, 8(2), 83–100.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xia, X., & Wong, S.T.C. (2012). Concise review: a high-content screening approach to stem cell research and drug discovery. Stem Cells, 30(9), 1800–1807.

    Article  CAS  PubMed  Google Scholar 

  • Yang, J., Yu, K., Gong, Y., Huang, T. (2009). Linear spatial pyramid matching using sparse coding for image classification. In Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (pp. 1794–1801).

  • Yu, D., Yang, F., Yang, C., Leng, C., Cao, J., Wang, Y., Tian, J. (2016). Fast rotation-free feature-based image registration using improved N-SIFT, and GMM-based parallel optimization. IEEE Transactions on Biomedical Engineering, 63(8), 1653–1664.

    Article  PubMed  Google Scholar 

  • Zhang, Y., Zhou, X., Degterev, A., Lipinski, M., Adjeroh, D., Yuan, J., Wong, S.T.C. (2007). A novel tracing algorithm for high throughput imaging: screening of neuron-based assays. Journal of Neuroscience Methods, 160(1), 149–162.

    Article  PubMed  Google Scholar 

  • Zhang, R., Zhou, W., Li, Y., Yu, S., Xie, Y. (2013). Nonrigid registration of lung CT images based on tissue features. Computational and Mathematical Methods in Medicine, 2013, 834192.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was partially supported by the Spanish Ministry of Economy, Industry and Competitiveness (project numbers MTM2014-54151-P, UNLC08-1E-002, UNLC13-13-3503), the University of La Rioja (project number FPI-UR-13), the European Regional Development Fund (FEDER) of the European Union, the Netherlands Organization for Scientific Reseach (project number 612.001.018), and the Erasmus University Medical Center Fellowship Program. Carlos Fernandez-Lozano was supported by a Juan de la Cierva postdoctoral fellowship grant (Spanish Ministry of Economy, Industry and Competitiveness, FJCI-2015-26071).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gadea Mata.

Additional information

Gadea Mata, Miroslav Radojević and Carlos Fernandez-Lozano contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mata, G., Radojević, M., Fernandez-Lozano, C. et al. Automated Neuron Detection in High-Content Fluorescence Microscopy Images Using Machine Learning. Neuroinform 17, 253–269 (2019). https://doi.org/10.1007/s12021-018-9399-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12021-018-9399-4

Keywords

Navigation