Dataset Information

Identification of "BRAF-Positive" Cases Based on Whole-Slide Image Analysis.

ABSTRACT: A key requirement for precision medicine is the accurate identification of patients that would respond to a specific treatment or those that represent a high-risk group, and a plethora of molecular biomarkers have been proposed for this purpose during the last decade. Their application in clinical settings, however, is not always straightforward due to relatively high costs of some tests, limited availability of the biological material and time, and procedural constraints. Hence, there is an increasing interest in constructing tissue-based surrogate biomarkers that could be applied with minimal overhead directly to histopathology images and which could be used for guiding the selection of eventual further molecular tests. In the context of colorectal cancer, we present a method for constructing a surrogate biomarker that is able to predict with high accuracy whether a sample belongs to the "BRAF-positive" group, a high-risk group comprising V600E BRAF mutants and BRAF-mutant-like tumors. Our model is trained to mimic the predictions of a 64-gene signature, the current definition of BRAF-positive group, thus effectively identifying histopathology image features that can be linked to a molecular score. Since the only required input is the routine histopathology image, the model can easily be integrated in the diagnostic workflow.

SUBMITTER: Popovici V

PROVIDER: S-EPMC5421098 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Identification of "BRAF-Positive" Cases Based on Whole-Slide Image Analysis.

Popovici Vlad V Křenek Aleš A Budinská Eva E

BioMed research international 20170424

A key requirement for precision medicine is the accurate identification of patients that would respond to a specific treatment or those that represent a high-risk group, and a plethora of molecular biomarkers have been proposed for this purpose during the last decade. Their application in clinical settings, however, is not always straightforward due to relatively high costs of some tests, limited availability of the biological material and time, and procedural constraints. Hence, there is an inc ...[more]

PMID: 28523274

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Project description:For a method to be widely adopted in medical research or clinical practice, it needs to be reproducible so that clinicians and regulators can have confidence in its use. Machine learning and deep learning have a particular set of challenges around reproducibility. Small differences in the settings or the data used for training a model can lead to large differences in the outcomes of experiments. In this work, three top-performing algorithms from the Camelyon grand challenges are reproduced using only information presented in the associated papers and the results are then compared to those reported. Seemingly minor details were found to be critical to performance and yet their importance is difficult to appreciate until the actual reproduction is attempted. We observed that authors generally describe the key technical aspects of their models well but fail to maintain the same reporting standards when it comes to data preprocessing which is essential to reproducibility. As an important contribution of the present study and its findings, we introduce a reproducibility checklist that tabulates information that needs to be reported in histopathology ML-based work in order to make it reproducible. Author summary For a method to be used a lot in medical research or clinical practice, it needs to be able to be reproduced so that people can trust it. Machine learning and deep learning have some challenges around this. For example, small changes in how a model is trained can lead to significant changes in the results of experiments. This makes it essential that researchers report how they do things in enough detail for the results of their experiments to be reproducible. In this work, we looked at three different algorithms used for digital pathology image analysis. We tried to reproduce them using only the information reported in their papers. We confirmed that even minor details could be essential. Authors often do not report all the details needed to reproduce their work. We also created a checklist of things that need to be reported to help other researchers make their work reproducible.

Project description:Digital pathology coupled with advanced machine learning (e.g., deep learning) has been changing the paradigm of whole-slide histopathological images (WSIs) analysis. Major applications in digital pathology using machine learning include automatic cancer classification, survival analysis, and subtyping from pathological images. While most pathological image analyses are based on patch-wise processing due to the extremely large size of histopathology images, there are several applications that predict a single clinical outcome or perform pathological diagnosis per slide (e.g., cancer classification, survival analysis). However, current slide-based analyses are task-dependent, and a general framework of slide-based analysis in WSI has been seldom investigated. We propose a novel slide-based histopathology analysis framework that creates a WSI representation map, called HipoMap, that can be applied to any slide-based problems, coupled with convolutional neural networks. HipoMap converts a WSI of various shapes and sizes to structured image-type representation. Our proposed HipoMap outperformed existing methods in intensive experiments with various settings and datasets. HipoMap showed the Area Under the Curve (AUC) of 0.96±0.026 (5% improved) in the experiments for lung cancer classification, and c-index of 0.787±0.013 (3.5% improved) and coefficient of determination ([Formula: see text]) of 0.978±0.032 (24% improved) in survival analysis and survival prediction with TCGA lung cancer data respectively, as a general framework of slide-based analysis with a flexible capability. The results showed significant improvement comparing to the current state-of-the-art methods on each task. We further discussed experimental results of HipoMap as pathological viewpoints and verified the performance using publicly available TCGA datasets. A Python package is available at https://pypi.org/project/hipomap , and the package can be easily installed using Python PIP. The open-source codes in Python are available at: https://github.com/datax-lab/HipoMap .

Project description:Histopathology tissue analysis is considered the gold standard in cancer diagnosis and prognosis. Whole-slide imaging (WSI), i.e., the scanning and digitization of entire histology slides, are now being adopted across the world in pathology labs. Trained histopathologists can provide an accurate diagnosis of biopsy specimens based on WSI data. Given the dimensionality of WSIs and the increase in the number of potential cancer cases, analyzing these images is a time-consuming process. Automated segmentation of tumorous tissue helps in elevating the precision, speed, and reproducibility of research. In the recent past, deep learning-based techniques have provided state-of-the-art results in a wide variety of image analysis tasks, including the analysis of digitized slides. However, deep learning-based solutions pose many technical challenges, including the large size of WSI data, heterogeneity in images, and complexity of features. In this study, we propose a generalized deep learning-based framework for histopathology tissue analysis to address these challenges. Our framework is, in essence, a sequence of individual techniques in the preprocessing-training-inference pipeline which, in conjunction, improve the efficiency and the generalizability of the analysis. The combination of techniques we have introduced includes an ensemble segmentation model, division of the WSI into smaller overlapping patches while addressing class imbalances, efficient techniques for inference, and an efficient, patch-based uncertainty estimation framework. Our ensemble consists of DenseNet-121, Inception-ResNet-V2, and DeeplabV3Plus, where all the networks were trained end to end for every task. We demonstrate the efficacy and improved generalizability of our framework by evaluating it on a variety of histopathology tasks including breast cancer metastases (CAMELYON), colon cancer (DigestPath), and liver cancer (PAIP). Our proposed framework has state-of-the-art performance across all these tasks and is ranked within the top 5 currently for the challenges based on these datasets. The entire framework along with the trained models and the related documentation are made freely available at GitHub and PyPi. Our framework is expected to aid histopathologists in accurate and efficient initial diagnosis. Moreover, the estimated uncertainty maps will help clinicians to make informed decisions and further treatment planning or analysis.

Dataset Information

Identification of "BRAF-Positive" Cases Based on Whole-Slide Image Analysis.

Publications

Identification of "BRAF-Positive" Cases Based on Whole-Slide Image Analysis.

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