Ontological Levels in Histological Imaging

Paper presented at the 9th edition of the Formal Ontology in Information Systems conference, FOIS 2016, July 6–9, 2016, Annecy, FranceThis is the author accepted manuscript. The final version is available from IOS Press via the DOI in this record.In this paper we present an ontological perspective on ongoing work in histological and histopathological imaging involving the quantitative and algorithmic analysis of digitised images of cells and tissues. We present the derivation of consistent histological models from initially captured images of prepared tissue samples as a progression through a number of ontological levels, each populated by its distinctive classes of entities related in systematic ways to entities at other levels. We see this work as contributing to ongoing efforts to provide a consistent and widely accepted suite of ontological resources such as those currently constituting the OBO Foundry, and where possible we draw links between our work and existing ontologies within that suite.This research is supported by EPSRC through funding under grant EP/M023869/1 “Novel context-based segmentation algorithms for intelligent microscopy”

Developing the Quantitative Histopathology Image Ontology : A case study using the hot spot detection problem

Interoperability across data sets is a key challenge for quantitative histopathological imaging. There is a need for an ontology that can support effective merging of pathological image data with associated clinical and demographic data. To foster organized, cross-disciplinary, information-driven collaborations in the pathological imaging field, we propose to develop an ontology to represent imaging data and methods used in pathological imaging and analysis, and call it Quantitative Histopathological Imaging Ontology – QHIO. We apply QHIO to breast cancer hot-spot detection with the goal of enhancing reliability of detection by promoting the sharing of data between image analysts

An improved ontological representation of dendritic cells as a paradigm for all cell types

The Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method to develop a dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’

The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology

Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone/marrow organoid in vivo

Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilage in vitro. Furthermore, upon in vivo transplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using this in vivo model, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche. CB ossicles were regularly observed upon transplantation. Compared with BM ossicles, CB ossicles showed a predominance of red marrow over yellow marrow, as demonstrated by histomorphological analyses and the number of hematopoietic cells isolated within ossicles. Marrow cavities from CB and BM ossicles included donor-derived CD146-expressing osteoprogenitors and host-derived mature hematopoietic cells, clonogenic lineage-committed progenitors and HSCs. Furthermore, human CD34+ cells transplanted into ossicle-bearing mice engrafted and maintained human HSCs in the niche. Our data indicate that CB- BFs are able to recapitulate the conditions by which the bone marrow microenvironment is formed and establish complete HSC niches, which are functionally supportive of hematopoietic tissue

When alarm bells ring: emergency tinnitus

OBJECTIVE: The aim of this study is to develop a diagnostic-therapeutic algorithm for those suffering from tinnitus who seek emergency aid. MATERIALS AND METHODS: A literature review has been performed on articles from the last 30 years. RESULTS: It is important to activate medical or surgical diagnostic and therapeutic strategies, in order to safeguard and rehabilitate the various functions affected. Psychiatric comorbidity is the most frequent pathological condition of those with serious or catastrophic tinnitus. In these cases, mortality risk is linked to suicide, morbidity to tinnitus-correlated distress. CONCLUSIONS: Tinnitus, mainly linked to loss of hearing, is a frequent symptom among the population at large. About 7% of those affected by tinnitus turn to their doctor to solve their problem, while between 0.5 and 2% request urgent medical assistance. Their cry for help may be the result of an acute onset of tinnitus or the rapid impairment of an already chronic condition. Tinnitus is not considered an urgent ear, nose and throat (ENT) condition by the Associazione Otorinolaringologi Ospedalieri Italiani (AOOI) [Italian Association of Hospital ENT], even though there are many pathological conditions, sometimes serious, associated with tinnitus and emergency action is necessary to reduce the risk of morbidity and mortality

A framework for systematic promoter motif discovery and expression profiling from high dimensional brain transcriptome data

Understanding the regulatory logic of genes across discrete brain substructures can elucidate the basis for neural network connectivity and the cause of disease. Promoter motifs, in particular, that govern high or low expression gene networks present an important fulcrum for phenotypic behavior. Using the Allen Institute Brain Atlas we took various clustering approaches to find closely regulated genes, and generated substructure specific expression profiles to run through FIRE, a motif discovery algorithm and iPAGE, a functional ontology algorithm. Notably, we found a single large cluster of genes that had tightly coordinated behavior across hundreds of brain substructures, as well as a unique upstream promoter signature, yet highly diverse ontological characteristics. We also present a BRain EXpression Profile ASSembly script (BEXPASS) whose output is customized for FIRE and iPAGE input. Lastly we look at language processing and speech control areas of the brain and put forward recommendations for promoters that can serve as part of DNA constructs for optogenetic research an emerging neuroscientific research method that uses bacterial light-gated ion channel protein, channelrhodopsin (ChR1 or ChR2), as an activity control tool to activate neural pathway signaling

Integración de datos de imagen molecular y expresión génica

As far as all the background information about atlases and gene expression databases has already been analysed, now we need to define further the project, its objectives and facts of interest. Gene expression databases, in most cases, do not provide any kind of integration with anatomical information of where those genes are expressed. The characterization of the whole transcriptome for structures like the brain is of limited utility if we have no anatomical information. Combining the databases with the anatomical information provided by an anatomical atlas, we can have lots of advantages. First of all, the most immediate advantage that such integration would introduce would be user-friendliness. Part of this problem is solved with the aGEM tool already developed, that integrates different databases into a single user interface.Visual representation of the gene locations would improve user experience if it is integrated with aGEM. As a second advantage, this integration could facilitate the connection between imaging and gene expression information when defining or analysing results from preclinical experiments. The definition of an imaging protocol in order to study the phenotype of a transgenic animal model could benefit from the results of this project, since the researcher could look for anatomical structures related to the genes that have been manipulated. The results of image quantification are usually an statistical parametric map, that presents the statistical significance of a certain analysis for every voxel. Significant areas from this image could be related to the underlying genes by means of the proposed integration tool. So, the main objective of the project is to connect all the information provided by aGEM and by the atlas. For the issue, it is needed to find how the information is stored and related in aGEM, in order to extract enough information of interest to program a first version of the tool. Also, it is required to study which atlases are available and which one is the most suitable for our purposes. Once all these steps have been done, the kind of program which is going to be developed needs to be analysed. There are several possibilities, like a program in Java, C++, Matlab or a plugin for its integration in ImageJ. Once all the necessary information is extracted, an integration step must be done for the program to be operative. Then, when the information mapping is ready, the interface of the program can be written. The first version of program should be able to perform certain query types: 1. Anatomy query: Given a list of anatomy structures, the user should be able to select any of them and the program would launch a query showing the genes and their information expressed in the structure, which would be shown in the atlas images. 2. Gene query: The user selects a gene and the program would detect in which structures is the gene expressed and show them in the atlas images. The purpose in a first stage is to integrate part of the information contained in aGEM in a beta trial version of the interface, in order to check its real utility.Ingeniería Biomédic

Bmi1 Controls Tumor Development in an Ink4a/Arf-Independent Manner in a Mouse Model for Glioma

SummaryThe Polycomb group and oncogene Bmi1 is required for the proliferation of various differentiated cells and for the self-renewal of stem cells and leukemic cancer stem cells. Repression of the Ink4a/Arf locus is a well described mechanism through which Bmi1 can exert its proliferative effects. However, we now demonstrate in an orthotopic transplantation model for glioma, a type of cancer harboring cancer stem cells, that Bmi1 is also required for tumor development in an Ink4a/Arf-independent manner. Tumors derived from Bmi1;Ink4a/Arf doubly deficient astrocytes or neural stem cells have a later time of onset and different histological grading. Moreover, in the absence of Ink4a/Arf, Bmi1-deficient cells and tumors display changes in differentiation capacity