Ontology-based surgical workflow recognition and prediction.

BACKGROUND: Surgical context-aware systems can adapt to the current situation in the operating room and thus provide computer-aided assistance functionalities and intraoperative decision-support. To interact with the surgical team perceptively and assist the surgical process, the system needs to monitor the intraoperative activities, understand the current situation in the operating room at any time, and anticipate the following possible situations. METHODS: A structured representation of surgical process knowledge is a prerequisite for any applications in the intelligent operating room. For this purpose, a surgical process ontology, which is formally based on standard medical terminology (SNOMED CT) and an upper-level ontology (GFO), was developed and instantiated for a neurosurgical use case. A new ontology-based surgical workflow recognition and a novel prediction method are presented utilizing ontological reasoning, abstraction, and explication. This way, a surgical situation representation with combined phase, high-level task, and low-level task recognition and prediction was realized based on the currently used instrument as the only input information. RESULTS: The ontology-based approach performed efficiently, and decent accuracy was achieved for situation recognition and prediction. Especially during situation recognition, the missing sensor information were reasoned based on the situation representation provided by the process ontology, which resulted in improved recognition results compared to the state-of-the-art. CONCLUSIONS: In this work, a reference ontology was developed, which provides workflow support and a knowledge base for further applications in the intelligent operating room, for instance, context-aware medical device orchestration, (semi-) automatic documentation, and surgical simulation, education, and training.

The Leipzig Health Atlas-An Open Platform to Present, Archive, and Share Biomedical Data, Analyses, and Models Online.

BACKGROUND: Clinical trials, epidemiological studies, clinical registries, and other prospective research projects, together with patient care services, are main sources of data in the medical research domain. They serve often as a basis for secondary research in evidence-based medicine, prediction models for disease, and its progression. This data are often neither sufficiently described nor accessible. Related models are often not accessible as a functional program tool for interested users from the health care and biomedical domains. OBJECTIVE: The interdisciplinary project Leipzig Health Atlas (LHA) was developed to close this gap. LHA is an online platform that serves as a sustainable archive providing medical data, metadata, models, and novel phenotypes from clinical trials, epidemiological studies, and other medical research projects. METHODS: Data, models, and phenotypes are described by semantically rich metadata. The platform prefers to share data and models presented in original publications but is also open for nonpublished data. LHA provides and associates unique permanent identifiers for each dataset and model. Hence, the platform can be used to share prepared, quality-assured datasets and models while they are referenced in publications. All managed data, models, and phenotypes in LHA follow the FAIR principles, with public availability or restricted access for specific user groups. RESULTS: The LHA platform is in productive mode (https://www.health-atlas.de/). It is already used by a variety of clinical trial and research groups and is becoming increasingly popular also in the biomedical community. LHA is an integral part of the forthcoming initiative building a national research data infrastructure for health in Germany.

Ontological Modelling and Execution of Phenotypic Queries in the Leipzig Health Atlas.

Sharing data is of great importance for research in medical sciences. It is the basis for reproducibility and reuse of already generated outcomes in new projects and in new contexts. FAIR data principles are the basics for sharing data. The Leipzig Health Atlas (LHA) platform follows these principles and provides data, describing metadata, and models that have been implemented in novel software tools and are available as demonstrators. LHA reuses and extends three different major components that have been previously developed by other projects. The SEEK management platform is the foundation providing a repository for archiving, presenting and secure sharing a wide range of publication results, such as published reports, (bio)medical data as well as interactive models and tools. The LHA Data Portal manages study metadata and data allowing to search for data of interest. Finally, PhenoMan is an ontological framework for phenotype modelling. This paper describes the interrelation of these three components. In particular, we use the PhenoMan to, firstly, model and represent phenotypes within the LHA platform. Then, secondly, the ontological phenotype representation can be used to generate search queries that are executed by the LHA Data Portal. The PhenoMan generates the queries in a novel domain specific query language (SDQL), which is specific for data management systems based on CDISC ODM standard, such as the LHA Data Portal. Our approach was successfully applied to represent phenotypes in the Leipzig Health Atlas with the possibility to execute corresponding queries within the LHA Data Portal.

Ontological representation, classification and data-driven computing of phenotypes.

BACKGROUND: The successful determination and analysis of phenotypes plays a key role in the diagnostic process, the evaluation of risk factors and the recruitment of participants for clinical and epidemiological studies. The development of computable phenotype algorithms to solve these tasks is a challenging problem, caused by various reasons. Firstly, the term 'phenotype' has no generally agreed definition and its meaning depends on context. Secondly, the phenotypes are most commonly specified as non-computable descriptive documents. Recent attempts have shown that ontologies are a suitable way to handle phenotypes and that they can support clinical research and decision making. The SMITH Consortium is dedicated to rapidly establish an integrative medical informatics framework to provide physicians with the best available data and knowledge and enable innovative use of healthcare data for research and treatment optimisation. In the context of a methodological use case 'phenotype pipeline' (PheP), a technology to automatically generate phenotype classifications and annotations based on electronic health records (EHR) is developed. A large series of phenotype algorithms will be implemented. This implies that for each algorithm a classification scheme and its input variables have to be defined. Furthermore, a phenotype engine is required to evaluate and execute developed algorithms. RESULTS: In this article, we present a Core Ontology of Phenotypes (COP) and the software Phenotype Manager (PhenoMan), which implements a novel ontology-based method to model, classify and compute phenotypes from already available data. Our solution includes an enhanced iterative reasoning process combining classification tasks with mathematical calculations at runtime. The ontology as well as the reasoning method were successfully evaluated with selected phenotypes including SOFA score, socio-economic status, body surface area and WHO BMI classification based on available medical data. CONCLUSIONS: We developed a novel ontology-based method to model phenotypes of living beings with the aim of automated phenotype reasoning based on available data. This new approach can be used in clinical context, e.g., for supporting the diagnostic process, evaluating risk factors, and recruiting appropriate participants for clinical and epidemiological studies.

Ontology patterns for the representation of quality changes of cells in time.

BACKGROUND: Cell tracking experiments, based on time-lapse microscopy, have become an important tool in biomedical research. The goal is the reconstruction of cell migration patterns, shape and state changes, and, comprehensive genealogical information from these data. This information can be used to develop process models of cellular dynamics. However, so far there has been no structured, standardized way of annotating and storing the tracking results, which is critical for comparative analysis and data integration. The key requirement to be satisfied by an ontology is the representation of a cell's change over time. Unfortunately, popular ontology languages, such as Web Ontology Language (OWL), have limitations for the representation of temporal information. The current paper addresses the fundamental problem of modeling changes of qualities over time in biomedical ontologies specified in OWL. RESULTS: The presented analysis is a result of the lessons learned during the development of an ontology, intended for the annotation of cell tracking experiments. We present, discuss and evaluate various representation patterns for specifying cell changes in time. In particular, we discuss two patterns of temporally changing information: n-ary relation reification and 4d fluents. These representation schemes are formalized within the ontology language OWL and are aimed at the support for annotation of cell tracking experiments. We analyze the performance of each pattern with respect to standard criteria used in software engineering and data modeling, i.e. simplicity, scalability, extensibility and adequacy. We further discuss benefits, drawbacks, and the underlying design choices of each approach. CONCLUSIONS: We demonstrate that patterns perform differently depending on the temporal distribution of modeled information. The optimal model can be constructed by combining two competitive approaches. Thus, we demonstrate that both reification and 4d fluents patterns can work hand in hand in a single ontology. Additionally, we have found that 4d fluents can be reconstructed by two patterns well known in the computer science community, i.e. state modeling and actor-role pattern.

Spreadsheet Model Generator (SMOG): A Lightweight Tool for Object-Spreadsheet Mapping.

In the life science domain, experts are usually familiar with spreadsheet software and often use it in their daily work to collect and structure required domain knowledge. The processing and analysis of spreadsheet data is an important task that must be supported by efficient software solutions. A typical application scenario is for example an integration of spreadsheet data (specified or derived) in an ontology to provide reasoning or search. Different converter tools were developed to support a spreadsheet-to-ontology transformation. Such tools allow often only a relatively simple structure of the spreadsheet template or they require complex mapping processes to map the spreadsheet and ontological entities. In many cases, it is impossible to use the existing converter tools because the spreadsheet data must be processed first before the derived data can be integrated into the ontology. In such cases, an efficient and fast development of customized software solutions is of great importance. In this paper, we present a general spreadsheet processing framework to efficiently read and write spreadsheet data. The Spreadsheet Model Generator (SMOG) provides a simple mechanism to automatically generate the Java object model and mappings between object code and spreadsheet entities. Our solution greatly simplifies the implementation of spreadsheet access methods and enables an efficient development of spreadsheet-based applications. The SMOG has already been used successfully in several biomedical projects under real world conditions.

Ontology-based specification and generation of search queries for post-market surveillance.

BACKGROUND: The vigilant observation of medical devices during post-market surveillance (PMS) for identifying safety-relevant incidents is a non-trivial task. A wide range of sources has to be monitored in order to integrate all accessible data about the safety and performance of a medical device. PMS needs to be supported by an efficient search strategy and the possibility to create complex search queries by domain experts. RESULTS: We use ontologies to support the specification of search queries and the preparation of the document corpus, which contains all relevant documents. In this paper, we present (1) the Search Ontology (SON) v2.0, (2) an Excel template for specifying search queries, and (3) the Search Ontology Generator (SONG), which generates complex queries out of the Excel template. Based on our approach, a service-oriented architecture was designed, which supports and assists domain experts during PMS. Comprehensive testing confirmed the correct execution of all SONG functions. The applicability of our method and of the developed tools was evaluated by domain experts. The test persons concordantly rated our solution after a short period of training as highly user-friendly, intuitive and well applicable for supporting PMS. CONCLUSIONS: The Search Ontology is a promising domain-independent approach to specify complex search queries. Our solution allows advanced searches for relevant documents in different domains using suitable domain ontologies.

An ontological framework for the formalization, organization and usage of TCM-Knowledge.

BACKGROUND: The traditional Chinese Medicine Language System (TCMLS) is a large-scale terminology system, developed from 2002 on by the Institute of Information of Traditional Chinese Medicine (IITCM). Until now, more than 120,000 concepts, 300,000 terms and 1.27 million semantic relational links are included. Its top-level framework, called TCMLS-semantic network (SN), provides an important basis for the standardization and mapping of traditional Chinese Medicine (TCM) terminology systems. Though, many data produced and stored in TCMLS have poor quality for historical reasons or because of human factors. There is a large number of classification errors or inconsistent expressions of terms remained in the current TCMLS- SN, which hamper an efficient utilization of the data stored in TCMLS in practical applications. METHODS: We start with analyzing the technical specification based on TCMLS, considering some obvious classification errors and problems of ambiguity of semantic expressions in TCMLS-SN, followed with using a top-down approach for building a middle level ontology which is based on the framework General Formal Ontology (GFO), take into account the compatibility with TCM related concepts, turn out the results of a modification of the current TCMLS-SN, called GFO-TCM. RESULTS: Through comparison with TCMLS-SN, according to viewpoints of GFO, some semantic types and relations were reconstructed within GFO-TCM. We propose a middle level ontology for TCMLS which may support entailment and ensure coherence, we also draw out a mapping which possess a more reasonable framework with a unified semantic criterion, it is application scenarios oriented and can be further updated and extended. CONCLUSIONS: The goal is to construct a formal middle-level ontology that is compatible with both the traditional medical terminology system and modern medical terminology standards. it is intended to satisfy functional requirements which are relevant for natural language processing, information extraction, semantic retrieval, clinical decision support in the field of traditional Chinese medicine. It also provides a foundation and methodology for building a large-scale, unified semantic and extensible knowledge graph platform.

Ontology-Guided Markerless Navigation and Situational Awareness for Endoscopic Surgery.

Optical navigation systems help surgeons find their way through the complex anatomy of a patient. However, such systems are accident-sensitive, time-consuming and difficult to use because of their complicated technical requirements such as the setting of optical markers and their intraoperative registration. The BIOPASS project, therefore, provides an innovative localisation system for markerless navigation in endoscopic surgery to support medical decision making. This system comprises several machine learning classifiers to recognise anatomical structures visible in the endoscopic images. To verify the data provided by these classifiers and to alert medical staff about surgical risk situations, we developed a new ontology-based software called OntoSun. Our software improves the precision and the sustainable traceability of the classifiers' results and also provides warning messages that increase situational awareness during surgical interventions.

Querying archetype-based EHRs by search ontology-based XPath engineering.

BACKGROUND: Legacy data and new structured data can be stored in a standardized format as XML-based EHRs on XML databases. Querying documents on these databases is crucial for answering research questions. Instead of using free text searches, that lead to false positive results, the precision can be increased by constraining the search to certain parts of documents. METHODS: A search ontology-based specification of queries on XML documents defines search concepts and relates them to parts in the XML document structure. Such query specification method is practically introduced and evaluated by applying concrete research questions formulated in natural language on a data collection for information retrieval purposes. The search is performed by search ontology-based XPath engineering that reuses ontologies and XML-related W3C standards. RESULTS: The key result is that the specification of research questions can be supported by the usage of search ontology-based XPath engineering. A deeper recognition of entities and a semantic understanding of the content is necessary for a further improvement of precision and recall. Key limitation is that the application of the introduced process requires skills in ontology and software development. In future, the time consuming ontology development could be overcome by implementing a new clinical role: the clinical ontologist. CONCLUSION: The introduced Search Ontology XML extension connects Search Terms to certain parts in XML documents and enables an ontology-based definition of queries. Search ontology-based XPath engineering can support research question answering by the specification of complex XPath expressions without deep syntax knowledge about XPaths.

Towards refactoring the Molecular Function Ontology with a UML profile for function modeling.

BACKGROUND: Gene Ontology (GO) is the largest resource for cataloging gene products. This resource grows steadily and, naturally, this growth raises issues regarding the structure of the ontology. Moreover, modeling and refactoring large ontologies such as GO is generally far from being simple, as a whole as well as when focusing on certain aspects or fragments. It seems that human-friendly graphical modeling languages such as the Unified Modeling Language (UML) could be helpful in connection with these tasks. RESULTS: We investigate the use of UML for making the structural organization of the Molecular Function Ontology (MFO), a sub-ontology of GO, more explicit. More precisely, we present a UML dialect, called the Function Modeling Language (FueL), which is suited for capturing functions in an ontologically founded way. FueL is equipped, among other features, with language elements that arise from studying patterns of subsumption between functions. We show how to use this UML dialect for capturing the structure of molecular functions. Furthermore, we propose and discuss some refactoring options concerning fragments of MFO. CONCLUSIONS: FueL enables the systematic, graphical representation of functions and their interrelations, including making information explicit that is currently either implicit in MFO or is mainly captured in textual descriptions. Moreover, the considered subsumption patterns lend themselves to the methodical analysis of refactoring options with respect to MFO. On this basis we argue that the approach can increase the comprehensibility of the structure of MFO for humans and can support communication, for example, during revision and further development.

Ontology-based specification, identification and analysis of perioperative risks.

BACKGROUND: Medical personnel in hospitals often works under great physical and mental strain. In medical decision-making, errors can never be completely ruled out. Several studies have shown that between 50 and 60% of adverse events could have been avoided through better organization, more attention or more effective security procedures. Critical situations especially arise during interdisciplinary collaboration and the use of complex medical technology, for example during surgical interventions and in perioperative settings (the period of time before, during and after surgical intervention). METHODS: In this paper, we present an ontology and an ontology-based software system, which can identify risks across medical processes and supports the avoidance of errors in particular in the perioperative setting. We developed a practicable definition of the risk notion, which is easily understandable by the medical staff and is usable for the software tools. Based on this definition, we developed a Risk Identification Ontology (RIO) and used it for the specification and the identification of perioperative risks. RESULTS: An agent system was developed, which gathers risk-relevant data during the whole perioperative treatment process from various sources and provides it for risk identification and analysis in a centralized fashion. The results of such an analysis are provided to the medical personnel in form of context-sensitive hints and alerts. For the identification of the ontologically specified risks, we developed an ontology-based software module, called Ontology-based Risk Detector (OntoRiDe). CONCLUSIONS: About 20 risks relating to cochlear implantation (CI) have already been implemented. Comprehensive testing has indicated the correctness of the data acquisition, risk identification and analysis components, as well as the web-based visualization of results.

Expert2OWL: A Methodology for Pattern-Based Ontology Development.

The formalization of expert knowledge enables a broad spectrum of applications employing ontologies as underlying technology. These include eLearning, Semantic Web and expert systems. However, the manual construction of such ontologies is time-consuming and thus expensive. Moreover, experts are often unfamiliar with the syntax and semantics of formal ontology languages such as OWL and usually have no experience in developing formal ontologies. To overcome these barriers, we developed a new method and tool, called Expert2OWL that provides efficient features to support the construction of OWL ontologies using GFO (General Formal Ontology) as a top-level ontology. This method allows a close and effective collaboration between ontologists and domain experts. Essentially, this tool integrates Excel spreadsheets as part of a pattern-based ontology development and refinement process. Expert2OWL enables us to expedite the development process and modularize the resulting ontologies. We applied this method in the field of Chinese Herbal Medicine (CHM) and used Expert2OWL to automatically generate an accurate Chinese Herbology ontology (CHO). The expressivity of CHO was tested and evaluated using ontology query languages SPARQL and DL. CHO shows promising results and can generate answers to important scientific questions such as which Chinese herbal formulas contain which substances, which substances treat which diseases, and which ones are the most frequently used in CHM.

Light-Weighted Automatic Import of Standardized Ontologies into the Content Management System Drupal.

The amount of ontologies, which are utilizable for widespread domains, is growing steadily. BioPortal alone, embraces over 500 published ontologies with nearly 8 million classes. In contrast, the vast informative content of these ontologies is only directly intelligible by experts. To overcome this deficiency it could be possible to represent ontologies as web portals, which does not require knowledge about ontologies and their semantics, but still carries as much information as possible to the end-user. Furthermore, the conception of a complex web portal is a sophisticated process. Many entities must be analyzed and linked to existing terminologies. Ontologies are a decent solution for gathering and storing this complex data and dependencies. Hence, automated imports of ontologies into web portals could support both mentioned scenarios. The Content Management System (CMS) Drupal 8 is one of many solutions to develop web presentations with less required knowledge about programming languages and it is suitable to represent ontological entities. We developed the Drupal Upper Ontology (DUO), which models concepts of Drupal's architecture, such as nodes, vocabularies and links. DUO can be imported into ontologies to map their entities to Drupal's concepts. Because of Drupal's lack of import capabilities, we implemented the Simple Ontology Loader in Drupal (SOLID), a Drupal 8 module, which allows Drupal administrators to import ontologies based on DUO. Our module generates content in Drupal from existing ontologies and makes it accessible by the general public. Moreover Drupal offers a tagging system which may be amplified with multiple standardized and established terminologies by importing them with SOLID. Our Drupal module shows that ontologies can be used to model content of a CMS and vice versa CMS are suitable to represent ontologies in a user-friendly way. Ontological entities are presented to the user as discrete pages with all appropriate properties, links and tags.

Processual Reasoning over Sequences of Situations in Endoscopic Surgery.

Minimally invasive surgery is a highly complex and technically demanding alternative to open surgery. Surgical procedures based on this method are characterized by small incisions and allow for a fast recovery of the patient. Such techniques are challenging for surgeons since they do not have a direct view of the surgical area. Systems that provide surgical navigation are well established in clinical practice but depend on external markers allowing a mapping between a surgeon's tools and a patient's medical images. As of today, these systems are prone to inaccuracies, the reasons of which lie in their extensive technical requirements. The BIOPASS project aims to develop an alternative that works without external markers and indirect computation of locations. An ontology has been used to provide an adequate vocabulary describing situations and their temporal relationship. This ontology is expected to relate real time multimodal sensor data and static surgical process models in order to infer movement directions, subsequent actions and hidden anatomical structures that inhere risk for surgical interventions. However, the Web Ontology Language is not capable of modelling temporal conditions, which are necessary to provide such exhaustive situational descriptions as expected by a surgeon. This paper concerns an ontology design pattern developed to overcome this issue by the integration of dynamic ontological classes that are assigned according to the temporal relations between situations.

Using Fast Healthcare Interoperability Resources (FHIR) for the Integration of Risk Minimization Systems in Hospitals.

With the growing strain of medical staff and complexity of patient care, the risk of medical errors increases. In this work we present the use of Fast Healthcare Interoperability Resources (FHIR) as communication standard for the integration of an ontology- and agent-based system to identify risks across medical processes in a clinical environment.

An Approach to Support Collaborative Ontology Construction.

The increasing number of terms used in textbooks for information management (IM) in hospitals makes it difficult for medical informatics students to grasp IM concepts and their interrelations. Formal ontologies which comprehend and represent the essential content of textbooks can facilitate the learning process in IM education. The manual construction of such ontologies is time-consuming and thus very expensive [3]. Moreover, most domain experts lack skills in using a formal language like OWL [2] and usually have no experience with standard editing tools like Protégé http://protege.stanford.edu [4,5]. This paper presents an ontology modeling approach based on Excel2OWL, a self-developed tool which efficiently supports domain experts in collaboratively constructing ontologies from textbooks. This approach was applied to classic IM textbooks, resulting in an ontology called SNIK. Our method facilitates the collaboration between domain experts and ontologists in the development process. Furthermore, the proposed approach enables ontologists to detect modeling errors and also to evaluate and improve the quality of the resulting ontology rapidly. This approach allows us to visualize the modeled textbooks and to analyze their semantics automatically. Hence, it can be used for e-learning purposes, particularly in the field of IM in hospitals.

OntoStudyEdit: a new approach for ontology-based representation and management of metadata in clinical and epidemiological research.

BACKGROUND: The specification of metadata in clinical and epidemiological study projects absorbs significant expense. The validity and quality of the collected data depend heavily on the precise and semantical correct representation of their metadata. In various research organizations, which are planning and coordinating studies, the required metadata are specified differently, depending on many conditions, e.g., on the used study management software. The latter does not always meet the needs of a particular research organization, e.g., with respect to the relevant metadata attributes and structuring possibilities. METHODS: The objective of the research, set forth in this paper, is the development of a new approach for ontology-based representation and management of metadata. The basic features of this approach are demonstrated by the software tool OntoStudyEdit (OSE). The OSE is designed and developed according to the three ontology method. This method for developing software is based on the interactions of three different kinds of ontologies: a task ontology, a domain ontology and a top-level ontology. RESULTS: The OSE can be easily adapted to different requirements, and it supports an ontologically founded representation and efficient management of metadata. The metadata specifications can by imported from various sources; they can be edited with the OSE, and they can be exported in/to several formats, which are used, e.g., by different study management software. CONCLUSIONS: Advantages of this approach are the adaptability of the OSE by integrating suitable domain ontologies, the ontological specification of mappings between the import/export formats and the DO, the specification of the study metadata in a uniform manner and its reuse in different research projects, and an intuitive data entry for non-expert users.

Towards improving phenotype representation in OWL.

BACKGROUND: Phenotype ontologies are used in species-specific databases for the annotation of mutagenesis experiments and to characterize human diseases. The Entity-Quality (EQ) formalism is a means to describe complex phenotypes based on one or more affected entities and a quality. EQ-based definitions have been developed for many phenotype ontologies, including the Human and Mammalian Phenotype ontologies. METHODS: We analyze formalizations of complex phenotype descriptions in the Web Ontology Language (OWL) that are based on the EQ model, identify several representational challenges and analyze potential solutions to address these challenges. RESULTS: In particular, we suggest a novel, role-based approach to represent relational qualities such as concentration of iron in spleen, discuss its ontological foundation in the General Formal Ontology (GFO) and evaluate its representation in OWL and the benefits it can bring to the representation of phenotype annotations. CONCLUSION: Our analysis of OWL-based representations of phenotypes can contribute to improving consistency and expressiveness of formal phenotype descriptions.

Semantic integration of physiology phenotypes with an application to the Cellular Phenotype Ontology.

MOTIVATION: The systematic observation of phenotypes has become a crucial tool of functional genomics, and several large international projects are currently underway to identify and characterize the phenotypes that are associated with genotypes in several species. To integrate phenotype descriptions within and across species, phenotype ontologies have been developed. Applying ontologies to unify phenotype descriptions in the domain of physiology has been a particular challenge due to the high complexity of the underlying domain. RESULTS: In this study, we present the outline of a theory and its implementation for an ontology of physiology-related phenotypes. We provide a formal description of process attributes and relate them to the attributes of their temporal parts and participants. We apply our theory to create the Cellular Phenotype Ontology (CPO). The CPO is an ontology of morphological and physiological phenotypic characteristics of cells, cell components and cellular processes. Its prime application is to provide terms and uniform definition patterns for the annotation of cellular phenotypes. The CPO can be used for the annotation of observed abnormalities in domains, such as systems microscopy, in which cellular abnormalities are observed and for which no phenotype ontology has been created. AVAILABILITY AND IMPLEMENTATION: The CPO and the source code we generated to create the CPO are freely available on http://cell-phenotype.googlecode.com.