Preliminary evaluation of the CellFinder literature curation pipeline for gene expression in kidney cells and anatomical parts

Biomedical literature curation is the process of automatically and/or manually deriving knowledge from scientific publications and recording it into specialized databases for structured delivery to users. It is a slow, error-prone, complex, costly and, yet, highly important task. Previous experiences have proven that text mining can assist in its many phases, especially, in triage of relevant documents and extraction of named entities and biological events. Here, we present the curation pipeline of the CellFinder database, a repository of cell research, which includes data derived from literature curation and microarrays to identify cell types, cell lines, organs and so forth, and especially patterns in gene expression. The curation pipeline is based on freely available tools in all text mining steps, as well as the manual validation of extracted data. Preliminary results are presented for a data set of 2376 full texts from which >4500 gene expression events in cell or anatomical part have been extracted. Validation of half of this data resulted in a precision of ~50% of the extracted data, which indicates that we are on the right track with our pipeline for the proposed task. However, evaluation of the methods shows that there is still room for improvement in the named-entity recognition and that a larger and more robust corpus is needed to achieve a better performance for event extraction. Database URL: http://www.cellfinder.org

CellFinder: a cell data repository

CellFinder (http://www.cellfinder.org) is a comprehensive one-stop resource for molecular data characterizing mammalian cells in different tissues and in different development stages. It is built from carefully selected data sets stemming from other curated databases and the biomedical literature. To date, CellFinder describes 3394 cell types and 50 951 cell lines. The database currently contains 3055 microscopic and anatomical images, 205 whole-genome expression profiles of 194 cell/tissue types from RNA-seq and microarrays and 553 905 protein expressions for 535 cells/tissues. Text mining of a corpus of >2000 publications followed by manual curation confirmed expression information on ∼900 proteins and genes. CellFinder's data model is capable to seamlessly represent entities from single cells to the organ level, to incorporate mappings between homologous entities in different species and to describe processes of cell development and differentiation. Its ontological backbone currently consists of 204 741 ontology terms incorporated from 10 different ontologies unified under the novel CELDA ontology. CellFinder's web portal allows searching, browsing and comparing the stored data, interactive construction of developmental trees and navigating the partonomic hierarchy of cells and tissues through a unique body browser designed for life scientists and clinicians

CELDA - an ontology for the comprehensive representation of cells in complex systems

BACKGROUND: The need for detailed description and modeling of cells drives the continuous generation of large and diverse datasets. Unfortunately, there exists no systematic and comprehensive way to organize these datasets and their information. CELDA (Cell: Expression, Localization, Development, Anatomy) is a novel ontology for the association of primary experimental data and derived knowledge to various types of cells of organisms. RESULTS: CELDA is a structure that can help to categorize cell types based on species, anatomical localization, subcellular structures, developmental stages and origin. It targets cells in vitro as well as in vivo. Instead of developing a novel ontology from scratch, we carefully designed CELDA in such a way that existing ontologies were integrated as much as possible, and only minimal extensions were performed to cover those classes and areas not present in any existing model. Currently, ten existing ontologies and models are linked to CELDA through the top-level ontology BioTop. Together with 15.439 newly created classes, CELDA contains more than 196.000 classes and 233.670 relationship axioms. CELDA is primarily used as a representational framework for modeling, analyzing and comparing cells within and across species in CellFinder, a web based data repository on cells (http://cellfinder.org). CONCLUSIONS: CELDA can semantically link diverse types of information about cell types. It has been integrated within the research platform CellFinder, where it exemplarily relates cell types from liver and kidney during development on the one hand and anatomical locations in humans on the other, integrating information on all spatial and temporal stages. CELDA is available from the CellFinder website: http://cellfinder.org/about/ontology

Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis

Epigenetic regulation of cell and tissue function requires the coordinated action of transcription factors. However, their combinatorial activities during regeneration remain largely unexplored. Here, we discover an unexpected interaction between the cytoprotective transcription factor NRF2 and p63-a key player in epithelial morphogenesis. Chromatin immunoprecipitation combined with sequencing and reporter assays identifies enhancers and promoters that are simultaneously activated by NRF2 and p63 in human keratinocytes. Modeling of p63 and NRF2 binding to nucleosomal DNA suggests their chromatin-assisted interaction. Pharmacological and genetic activation of NRF2 increases NRF2-p63 binding to enhancers and promotes keratinocyte proliferation, which involves the common NRF2-p63 target cyclin-dependent kinase 12. These results unravel a collaborative function of NRF2 and p63 in the control of epidermal renewal and suggest their combined activation as a strategy to promote repair of human skin and other stratified epithelia

Angle resolved photoelectron spectroscopy of two-color XUV-NIR ionization with polarization control

Electron emission caused by extreme ultraviolet (XUV) radiation in the presence of a strong near infrared (NIR) field leads to multiphoton interactions that depend on several parameters. Here, a comprehensive study of the influence of the angle between the polarization directions of the NIR and XUV fields on the two-color angle-resolved photoelectron spectra of He and Ne is presented. The resulting photoelectron angular distribution strongly depends on the orientation of the NIR polarization plane with respect to that of the XUV field. The prevailing influence of the intense NIR field over the angular emission characteristics for He(1s) and Ne(2p) ionization lines is shown. The underlying processes are modeled in the frame of the strong field approximation (SFA) which shows very consistent agreement with the experiment reaffirming the power of the SFA for multicolor-multiphoton ionization in this regime

A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity.

Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance. Comparative proteomics of cornified envelopes (CEs) from prenatal KtyI(-/-) and KtyII(-/-)(K8) mice demonstrates that absence of KIF causes dysregulation of many CE constituents, including downregulation of desmoglein 1. Despite persistence of loricrin expression and upregulation of many Nrf2 targets, including CE components Sprr2d and Sprr2h, extensive barrier defects persist, identifying keratins as essential CE scaffolds. Furthermore, we show that KIFs control mitochondrial lipid composition and activity in a cell-intrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation