Whole slide image registration for the study of tumor heterogeneity

Consecutive thin sections of tissue samples make it possible to study local variation in e.g. protein expression and tumor heterogeneity by staining for a new protein in each section. In order to compare and correlate patterns of different proteins, the images have to be registered with high accuracy. The problem we want to solve is registration of gigapixel whole slide images (WSI). This presents 3 challenges: (i) Images are very large; (ii) Thin sections result in artifacts that make global affine registration prone to very large local errors; (iii) Local affine registration is required to preserve correct tissue morphology (local size, shape and texture). In our approach we compare WSI registration based on automatic and manual feature selection on either the full image or natural sub-regions (as opposed to square tiles). Working with natural sub-regions, in an interactive tool makes it possible to exclude regions containing scientifically irrelevant information. We also present a new way to visualize local registration quality by a Registration Confidence Map (RCM). With this method, intra-tumor heterogeneity and charateristics of the tumor microenvironment can be observed and quantified.Comment: MICCAI2018 - Computational Pathology and Ophthalmic Medical Image Analysis - COMPA

MetNetAPI: A flexible method to access and manipulate biological network data from MetNet

<p>Abstract</p> <p>Background</p> <p>Convenient programmatic access to different biological databases allows automated integration of scientific knowledge. Many databases support a function to download files or data snapshots, or a webservice that offers "live" data. However, the functionality that a database offers cannot be represented in a static data download file, and webservices may consume considerable computational resources from the host server.</p> <p>Results</p> <p>MetNetAPI is a versatile Application Programming Interface (API) to the MetNetDB database. It abstracts, captures and retains operations away from a biological network repository and website. A range of database functions, previously only available online, can be immediately (and independently from the website) applied to a dataset of interest. Data is available in four layers: molecular entities, localized entities (linked to a specific organelle), interactions, and pathways. Navigation between these layers is intuitive (e.g. one can request the molecular entities in a pathway, as well as request in what pathways a specific entity participates). Data retrieval can be customized: Network objects allow the construction of new and integration of existing pathways and interactions, which can be uploaded back to our server. In contrast to webservices, the computational demand on the host server is limited to processing data-related queries only.</p> <p>Conclusions</p> <p>An API provides several advantages to a systems biology software platform. MetNetAPI illustrates an interface with a central repository of data that represents the complex interrelationships of a metabolic and regulatory network. As an alternative to data-dumps and webservices, it allows access to a current and "live" database and exposes analytical functions to application developers. Yet it only requires limited resources on the server-side (thin server/fat client setup). The API is available for Java, Microsoft.NET and R programming environments and offers flexible query and broad data- retrieval methods. Data retrieval can be customized to client needs and the API offers a framework to construct and manipulate user-defined networks. The design principles can be used as a template to build programmable interfaces for other biological databases. The API software and tutorials are available at <url>http://www.metnetonline.org/api</url>.</p

International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

BACKGROUND: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. METHODS: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined. RESULTS: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006). CONCLUSIONS: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies

PlantMetabolomics.org: A Web Portal for Plant Metabolomics Experiments1[C][W][OA]

PlantMetabolomics.org (PM) is a web portal and database for exploring, visualizing, and downloading plant metabolomics data. Widespread public access to well-annotated metabolomics datasets is essential for establishing metabolomics as a functional genomics tool. PM integrates metabolomics data generated from different analytical platforms from multiple laboratories along with the key visualization tools such as ratio and error plots. Visualization tools can quickly show how one condition compares to another and which analytical platforms show the largest changes. The database tries to capture a complete annotation of the experiment metadata along with the metabolite abundance databased on the evolving Metabolomics Standards Initiative. PM can be used as a platform for deriving hypotheses by enabling metabolomic comparisons between genetically unique Arabidopsis (Arabidopsis thaliana) populations subjected to different environmental conditions. Each metabolite is linked to relevant experimental data and information from various annotation databases. The portal also provides detailed protocols and tutorials on conducting plant metabolomics experiments to promote metabolomics in the community. PM currently houses Arabidopsis metabolomics data generated by a consortium of laboratories utilizing metabolomics to help elucidate the functions of uncharacterized genes. PM is publicly available at http://www.plantmetabolomics.org

International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

Background:Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs.Methods:Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined.Results:Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006).Conclusions:The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies

Computer-Aided Design and Manufacturing (CAD/CAM) for Bioprinting

Three-dimensional (3D) printing of human tissues and organs has been an exciting area of research for almost three decades [Bonassar and Vacanti. J Cell Biochem. 72(Suppl 30-31):297-303 (1998)]. The primary goal of bioprinting, presently, is achieving printed constructs with the overarching aim toward fully functional tissues and organs. Technology, in hand with the development of bioinks, has been identified as the key to this success. As a result, the place of computer-aided systems (design and manufacturing-CAD/CAM) cannot be underestimated and plays a significant role in this area. Unlike many reviews in this field, this chapter focuses on the technology required for 3D bioprinting from an initial background followed by the exciting area of medical imaging and how it plays a role in bioprinting. Extraction and classification of tissue types from 3D scans is discussed in addition to modeling and simulation capabilities of scanned systems. After that, the necessary area of transferring the 3D model to the printer is explored. The chapter closes with a discussion of the current state-of-the-art and inherent challenges facing the research domain to achieve 3D tissue and organ printing

International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

BACKGROUND: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. METHODS: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined. RESULTS: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006). CONCLUSIONS: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies