Bioimage Informatics for Systems Pharmacology

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1 Bioimage Informatics for Systems Pharmacology Authors : Fuhai Li Zheng Yin Guangxu Jin Hong Zhao Stephen T. C. Wong Presented by : Iffat chowdhury

2 Motivation Image is worth for phenotypic changes identification High resolution microscopy, fluorescent labeling Rich in terms of information of biological processes Bioimage informatics

3 Bioimage informatics

4 Image based Studies Example Multicolor cell imaging-based studies Live-cell imaging-based studies Neuron imaging-based studies C. elegans imaging-based studies

5 Image based Studies Example Multicolor cell imaging-based studies Live-cell imaging-based studies Neuron imaging-based studies C. elegans imaging-based studies

6 Multicolor cell imaging-based studies Multiple fluorescent markers Feature extraction Drosophila cell Softwares : CellProfiler, Fiji, Icy, GcellIQ, PhenoRipper

7 Multicolor cell imaging-based studies

8 Multicolor cell imaging-based studies Multiple fluorescent markers Feature extraction Drosophila cell Softwares : CellProfiler, Fiji, Icy, GcellIQ, PhenoRipper

9 Image based Studies Example Multicolor cell imaging-based studies Live-cell imaging-based studies Neuron imaging-based studies C. elegans imaging-based studies

10 Live-cell imaging-based studies Progression, proliferation, migration of cell Dynamic behaviors of cells Live Hela cell images Softwares : CellProfiler, Fiji, BioimageXD, Icy, CellCognition, DCellIQ, TLM-Tracker

11 Live-cell imaging-based studies

12 Live-cell imaging-based studies Progression, proliferation, migration of cell Dynamic behaviors of cells Live Hela cell images Softwares : CellProfiler, Fiji, BioimageXD, Icy, CellCognition, DCellIQ, TLM-Tracker

13 Image based Studies Example Multicolor cell imaging-based studies Live-cell imaging-based studies Neuron imaging-based studies C. elegans imaging-based studies

14 Neuron imaging-based studies To study brain functions and disorders Use super-resolution microscope Softwares : NeurphologyJ, NeuronJ, NeuriteTracer, NeuriteIQ, NeuronMetrics, NeuronStudio, Vaa3D

15 Neuron imaging-based studies

16 Neuron imaging-based studies To study brain functions and disorders Use super-resolution microscope Softwares : NeurphologyJ, NeuronJ, NeuriteTracer, NeuriteIQ, NeuronMetrics, NeuronStudio, Vaa3D

17 Neuron imaging-based studies

18 Image based Studies Example Multicolor cell imaging-based studies Live-cell imaging-based studies Neuron imaging-based studies C. elegans imaging-based studies

19 Caenorhabditis elegans imaging-based studies Common animal model for drug and target discovery Consists of only hundred of cells Embryonic development

20 Caenorhabditis elegans imaging-based studies Source : Wikipedia

21 Caenorhabditis elegans imaging-based studies Common animal model for drug and target discovery Consists of only hundred of cells Embryonic development

22 Bioimage informatics

23 Bioimage informatics

24 Object Detection Detect the locations of individual objects Facilitate the segmentation by giving the position and initial boundary information Two types of object detection : 1. Blob structure detection 2. Tube structure detection

25 Blob Structure Detection Nuclei detection Distance transformation Seeded watershed Intensity information Gradient vector

26 Blob Structure Detection

27 Blob Structure Detection Nuclei detection Distance transformation Seeded watershed Intensity information Gradient vector

28 Tube Structure Detection Intensity remains constant Centerline detection Edge detectors Machine-learning

29 Tube Structure Detection

30 Tube Structure Detection Intensity remains constant Centerline detection Edge detectors Machine-learning

31 Tube Structure Detection

32 Bioimage informatics

33 Object Segmentation Delineate boundaries of objects Threshold segmentation Fuzzy-C-Means method Watershed algorithm Active contour model Level set representation Voronoi segmentation Graph cut method Softwares : CellProfiler, Fiji, Ilastik, SLIC

34 Object Segmentation

35 Object Segmentation Delineate boundaries of objects Threshold segmentation Fuzzy-C-Means method Watershed algorithm Active contour model Level set representation Voronoi segmentation Graph cut method Softwares : CellProfiler, Fiji, Ilastik, SLIC

36 Object Segmentation Figure taken from

37 Object Segmentation

38 Object Segmentation Delineate boundaries of objects Threshold segmentation Fuzzy-C-Means method Watershed algorithm Active contour model Level set representation Voronoi segmentation Graph cut method Softwares : CellProfiler, Fiji, Ilastik, SLIC

39 Bioimage Informatics

40 Object Tracking Study dynamic behaviors Three approaches : 1. Model evolution based 2. Spatial-temporal volume segmentation based 3. Segmentation based

41 Object Tracking

42 Object Tracking Study dynamic behaviors Three approaches : 1. Model evolution based 2. Spatial-temporal volume segmentation based 3. Segmentation based

43 Object Tracking

44 Object Tracking Study dynamic behaviors Three approaches : 1. Model evolution based 2. Spatial-temporal volume segmentation based 3. Segmentation based

45 Object Tracking

46 Model Evolution Based Cell / nuclei are detected first Boundary comes next Contour model Different objects get different colors

47 Spatial-Temporal Volume Segmentation Based 2D image sequences as 3D Level set segmentation approaches

48 Segmentation Based First detected and then segmented Tracking is dependent of segmentation and detection Association Filters may be used

49 Bioimage Informatics

50 Image Visualization Fiji, Icy, BioimageXD are for higher dimensional data NeuronStudio for neuron image analysis Farsight and vaa3d for microscopy images For customize tools, Visualization Toolkit helps.

51 Numerical Features Quantitative measuring Four quantitative features 1. Wavelet feature 2. Geometry feature 3. Zernike feature 4. Haralick texture feature

52 Numerical Features Wavelet feature : characterize the images in both scale and frequency domain. Geometry feature : describe the shape and texture features. Zernike feature : projection and the use of Zernike moment. Haralick texture feature : use grey-level matrices

53 Phenotype Identification Cell cycle phase identification User defined phenotype, identification and classification

54 Cell Cycle Phase Identification Automated cell cycle phase identification is needed to calculate the dwelling time of individual cells in each phase. SVM, K-nearest neighbors, Bayesian classifiers Can be done during segmentation and tracking.

55 Cell Cycle Phase Identification

56 Cell Cycle Phase Identification Automated cell cycle phase identification is needed to calculate the dwelling time of individual cells in each phase. SVM, K-nearest neighbors, Bayesian classifiers Can be done during segmentation and tracking.

57 User Defined Phenotype, Identification and Classification Exhibit novel phenotype and unpredicted behaviors. Gaussian Mixture Model with statistics Clustering analysis Classifiers

58 User Defined Phenotype, Identification and Classification

59 User Defined Phenotype, Identification and Classification Exhibit novel phenotype and unpredicted behaviors. Gaussian Mixture Model with statistics Clustering analysis Classifiers

60 Multidimensional Profiling Analysis Clustering analysis SVM-based multivariate profiling analysis Factor-based multidimensional profiling analysis Subpopulation-based heterogeneity profiling analysis

61 Multidimensional Profiling Analysis Clustering analysis SVM-based multivariate profiling analysis Factor-based multidimensional profiling analysis Subpopulation-based heterogeneity profiling analysis

62 Clustering Analysis Experimental perturbations Softwares : Cluster 3.0, Java TreeView

63 Multidimensional Profiling Analysis Clustering analysis SVM-based multivariate profiling analysis Factor-based multidimensional profiling analysis Subpopulation-based heterogeneity profiling analysis

64 SVM-basheed Multivariate Profiling Analysis Wells with treated cells compared to wells with untreated cells. The differences are indicated by the outputs of SVM One is the accuracy and another is the normal vector of the hyperplane.

65 SVM-basheed Multivariate Profiling Analysis

66 Multidimensional Profiling Analysis Clustering analysis SVM-based multivariate profiling analysis Factor-based multidimensional profiling analysis Subpopulation-based heterogeneity profiling analysis

67 Factor-based Multidimensional Profiling Analysis Correlation of the features within the group and between the groups. Redundancy can be removed by factor analysis. Six factors representing nuclei size, DNA replication, chromosome condensation, nuclei morphology etc. by factor analysis.

68 Multidimensional Profiling Analysis Clustering analysis SVM-based multivariate profiling analysis Factor-based multidimensional profiling analysis Subpopulation-based heterogeneity profiling analysis

69 Subpopulation-based Heterogeneity Profiling Analysis Heterogeneous behavior within a cell population. GMM model to divide into subpopulation.

70 Exercises!!!

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