Dataset Information

Deep fusion of contextual and object-based representations for delineation of multiple nuclear phenotypes.

ABSTRACT: MOTIVATION:Nuclear delineation and phenotypic profiling are important steps in the automated analysis of histology sections. However, these are challenging problems due to (i) technical variations (e.g. fixation, staining) that originate as a result of sample preparation; (ii) biological heterogeneity (e.g. vesicular versus high chromatin phenotypes, nuclear atypia) and (iii) overlapping nuclei. This Application-Note couples contextual information about the cellular organization with the individual signature of nuclei to improve performance. As a result, routine delineation of nuclei in H&E stained histology sections is enabled for either computer-aided pathology or integration with genome-wide molecular data. RESULTS:The method has been evaluated on two independent datasets. One dataset originates from our lab and includes H&E stained sections of brain and breast samples. The second dataset is publicly available through IEEE with a focus on gland-based tissue architecture. We report an approximate AJI of 0.592 and an F1-score 0.93 on both datasets. AVAILABILITY AND IMPLEMENTATION:The code-base, modified dataset and results are publicly available. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

SUBMITTER: Khoshdeli M

PROVIDER: S-EPMC6853689 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Deep fusion of contextual and object-based representations for delineation of multiple nuclear phenotypes.

Khoshdeli Mina M Winkelmaier Garrett G Parvin Bahram B

Bioinformatics (Oxford, England) 20191101 22

<h4>Motivation</h4>Nuclear delineation and phenotypic profiling are important steps in the automated analysis of histology sections. However, these are challenging problems due to (i) technical variations (e.g. fixation, staining) that originate as a result of sample preparation; (ii) biological heterogeneity (e.g. vesicular versus high chromatin phenotypes, nuclear atypia) and (iii) overlapping nuclei. This Application-Note couples contextual information about the cellular organization with the ...[more]

PMID: 31135022

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Project description:BackgroundNuclear segmentation is an important step for profiling aberrant regions of histology sections. If nuclear segmentation can be resolved, then new biomarkers of nuclear phenotypes and their organization can be predicted for the application of precision medicine. However, segmentation is a complex problem as a result of variations in nuclear geometry (e.g., size, shape), nuclear type (e.g., epithelial, fibroblast), nuclear phenotypes (e.g., vesicular, aneuploidy), and overlapping nuclei. The problem is further complicated as a result of variations in sample preparation (e.g., fixation, staining). Our hypothesis is that (i) deep learning techniques can learn complex phenotypic signatures that rise in tumor sections, and (ii) fusion of different representations (e.g., regions, boundaries) contributes to improved nuclear segmentation.ResultsWe have demonstrated that training of deep encoder-decoder convolutional networks overcomes complexities associated with multiple nuclear phenotypes, where we evaluate alternative architecture of deep learning for an improved performance against the simplicity of the design. In addition, improved nuclear segmentation is achieved by color decomposition and combining region- and boundary-based features through a fusion network. The trained models have been evaluated against approximately 19,000 manually annotated nuclei, and object-level Precision, Recall, F1-score and Standard Error are reported with the best F1-score being 0.91. Raw training images, annotated images, processed images, and source codes are released as a part of the Additional file 1.ConclusionsThere are two intrinsic barriers in nuclear segmentation to H&E stained images, which correspond to the diversity of nuclear phenotypes and perceptual boundaries between adjacent cells. We demonstrate that (i) the encoder-decoder architecture can learn complex phenotypes that include the vesicular type; (ii) delineation of overlapping nuclei is enhanced by fusion of region- and edge-based networks; (iii) fusion of ENets produces an improved result over the fusion of UNets; and (iv) fusion of networks is better than multitask learning. We suggest that our protocol enables processing a large cohort of whole slide images for applications in precision medicine.

Dataset Information

Deep fusion of contextual and object-based representations for delineation of multiple nuclear phenotypes.

Publications

Deep fusion of contextual and object-based representations for delineation of multiple nuclear phenotypes.

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