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Pre-Meta: priors-augmented retrieval for LLM-based metadata generation.

MOTIVATION: While high-throughput sequencing technologies have dramatically accelerated genomic data generation, the manual processes required for dataset annotation and metadata creation impede the efficient discovery and publication of these resources across disparate public repositories. Large language models (LLMs) have the potential to streamline dataset profiling and discovery. However, their current limitations in generalizing across specialized knowledge domains, particularly in fields such as biomedical genomics, prevent them from fully realizing this potential. This article presents Pre-Meta, an LLM-agnostic and domain-independent data annotation pipeline with an enriched retrieval procedure that leverages related priors-such as pre-generated metadata tags and ontologies-as auxiliary information to improve the accuracy of automated metadata generation. RESULTS: Validated using five selected metadata fields sampled across 1500 papers, the Pre-Meta assisted annotation experiment-without finetuning and prompt optimization-demonstrates a systemic improvement in the annotation task: shown through a 23%, 72%, and 75% accuracy gain from conventional RAG adoptions of GPT-4o mini, Llama 8B, and Mistral 7B respectively. AVAILABILITY AND IMPLEMENTATION: The code, data access, and scripts are available at: https://github.com/SINTEF-SE/LLMDap.

Metadata↗

PYCHEM: a multivariate analysis package for python.

UNLABELLED: We have implemented a multivariate statistical analysis toolbox, with an optional standalone graphical user interface (GUI), using the Python scripting language. This is a free and open source project that addresses the need for a multivariate analysis toolbox in Python. Although the functionality provided does not cover the full range of multivariate tools that are available, it has a broad complement of methods that are widely used in the biological sciences. In contrast to tools like MATLAB, PyChem 2.0.0 is easily accessible and free, allows for rapid extension using a range of Python modules and is part of the growing amount of complementary and interoperable scientific software in Python based upon SciPy. One of the attractions of PyChem is that it is an open source project and so there is an opportunity, through collaboration, to increase the scope of the software and to continually evolve a user-friendly platform that has applicability across a wide range of analytical and post-genomic disciplines. AVAILABILITY: http://sourceforge.net/projects/pychem

Algorithms↗

Transparent ICD and DRG coding using information technology: linking and associating information sources with the eXtensible Markup Language.

With the introduction of ICD-10 as the standard for diagnostics, it becomes necessary to develop an electronic representation of its complete content, inherent semantics, and coding rules. The authors' design relates to the current efforts by the CEN/TC 251 to establish a European standard for hierarchical classification systems in health care. The authors have developed an electronic representation of ICD-10 with the eXtensible Markup Language (XML) that facilitates integration into current information systems and coding software, taking different languages and versions into account. In this context, XML provides a complete processing framework of related technologies and standard tools that helps develop interoperable applications. XML provides semantic markup. It allows domain-specific definition of tags and hierarchical document structure. The idea of linking and thus combining information from different sources is a valuable feature of XML. In addition, XML topic maps are used to describe relationships between different sources, or "semantically associated" parts of these sources. The issue of achieving a standardized medical vocabulary becomes more and more important with the stepwise implementation of diagnostically related groups, for example. The aim of the authors' work is to provide a transparent and open infrastructure that can be used to support clinical coding and to develop further software applications. The authors are assuming that a comprehensive representation of the content, structure, inherent semantics, and layout of medical classification systems can be achieved through a document-oriented approach.

Diagnosis-Related Groups↗

GLIF3: the evolution of a guideline representation format.

The Guideline Interchange Format (GLIF) is a language for structured representation of guidelines. It was developed to facilitate sharing clinical guidelines. GLIF version 2 enabled modeling a guideline as a flowchart of structured steps, representing clinical actions and decisions. However, the attributes of structured constructs were defined as text strings that could not be parsed, and such guidelines could not be used for computer-based execution that requires automatic inference. GLIF3 is a new version of GLIF designed to support computer-based execution. GLIF3 builds upon the framework set by GLIF2 but augments it by introducing several new constructs and extending GLIF2 constructs to allow a more formal definition of decision criteria, action specifications and patient data. GLIF3 enables guideline encoding at three levels: a conceptual flowchart, a computable specification that can be verified for logical consistency and completeness, and an implementable specification that can be incorporated into particular institutional information systems.

Decision Support Techniques↗

Qumquad: a UML-based approach for remodeling of legacy systems in health care.

OBJECTIVE: Health care information systems still comprise legacy systems to a certain extent. For reengineering legacy systems a thorough remodeling is inalienable. Current modeling techniques like the Unified Modeling Language (UML) do not offer a systematic and comprehensive process-oriented method for remodeling activities. METHOD: We developed a systematic method for remodeling legacy systems in health care called Qumquad. Qumquad consists of three major steps: (i) modeling the actual state of the application system, (ii) systematic identification of weak points in this model and (iii) development of a target concept for the reimplementation considering the identified weak points. RESULTS: We applied Qumquad for remodeling a documentation and therapy planning system for pediatric oncology (DOSPO). As a result of our remodeling activities we regained an abstract model of the system, an analysis of the current weak points of DOSPO and possible (partly alternative) solutions to overcome the weak points. DISCUSSION AND CONCLUSION: Qumquad proved to be very helpful in the reengineering process of DOSPO since we now have at our disposal a comprehensive model for the reimplementation of DOSPO that current users of the system agree on. Qumquad can easily be applied to other reengineering projects in health care.

Delivery of Health Care↗

Object-oriented design tools for supramolecular devices and biomedical nanotechnology.

Nanotechnology provides multifunctional agents for in vivo use that increasingly blur the distinction between pharmaceuticals and medical devices. Realization of such therapeutic nanodevices requires multidisciplinary effort that is difficult for individual device developers to sustain, and identification of appropriate collaborations outside ones own field can itself be challenging. Further, as in vivo nanodevices become increasingly complex, their design will increasingly demand systems level thinking. System engineering tools such as object-oriented analysis, object-oriented design (OOA/D) and unified modeling language (UML) are applicable to nanodevices built from biological components, help logically manage the knowledge needed to design them, and help identify useful collaborative relationships for device designers. We demonstrate the utility of these systems engineering tools by reverse engineering an existing molecular device (the bacmid molecular cloning system) using them, and illustrate how object-oriented approaches identify fungible components (objects) in nanodevices in a way that facilitates design of families of related devices, rather than single inventions. We also explore the utility of object-oriented approaches for design of another class of therapeutic nanodevices, vaccines. While they are useful for design of current nanodevices, the power of systems design tools for biomedical nanotechnology will become increasingly apparent as the complexity and sophistication of in vivo nanosystems increases. The nested, hierarchical nature of object-oriented approaches allows treatment of devices as objects in higher-order structures, and so will facilitate concatenation of multiple devices into higher-order, higher-function nanosystems.

Baculoviridae↗

Integrating digital educational content created and stored within disparate software environments: an extensible markup language (XML) solution in real-world use.

OBJECTIVE: To provide a standardized and scaleable mechanism for exchanging digital radiologic educational content between software systems that use disparate authoring, storage, and presentation technologies. MATERIALS/METHODS: Our institution uses two distinct software systems for creating educational content for radiology. Each system is used to create in-house educational content as well as commercial educational products. One system is an authoring and viewing application that facilitates the input and storage of hierarchical knowledge and associated imagery, and is capable of supporting a variety of entity relationships. This system is primarily used for the production and subsequent viewing of educational CD-ROMS. Another software system is primarily used for radiologic education on the world wide web. This system facilitates input and storage of interactive knowledge and associated imagery, delivering this content over the internet in a Socratic manner simulating in-person interaction with an expert. A subset of knowledge entities common to both systems was derived. An additional subset of knowledge entities that could be bidirectionally mapped via algorithmic transforms was also derived. An extensible markup language (XML) object model and associated lexicon were then created to represent these knowledge entities and their interactive behaviors. Forward-looking attention was exercised in the creation of the object model in order to facilitate straightforward future integration of other sources of educational content. XML generators and interpreters were written for both systems. RESULTS: Deriving the XML object model and lexicon was the most critical and time-consuming aspect of the project. The coding of the XML generators and interpreters required only a few hours for each environment. Subsequently, the transfer of hundreds of educational cases and thematic presentations between the systems can now be accomplished in a matter of minutes. The use of algorithmic transforms results in nearly 100% transfer of context as well as content, thus providing "presentation-ready" outcomes. CONCLUSION: The automation of knowledge exchange between dissimilar digital teaching environments magnifies the efforts of educators and enriches the learning experience for participants. XML is a powerful and useful mechanism for transfering educational content, as well as the context and interactive behaviors of such content, between disparate systems.

Computer Storage Devices↗

Building interactive virtual environments for simulated training in medicine using VRML and Java/JavaScript.

Medicine is a difficult thing to learn. Experimenting with real patients should not be the only option; simulation deserves a special attention here. Virtual Reality Modelling Language (VRML) as a tool for building virtual objects and scenes has a good record of educational applications in medicine, especially for static and animated visualisations of body parts and organs. However, to create computer simulations resembling situations in real environments the required level of interactivity and dynamics is difficult to achieve. In the present paper we describe some approaches and techniques which we used to push the limits of the current VRML technology further toward dynamic 3D representation of virtual environments (VEs). Our demonstration is based on the implementation of a virtual baby model, whose vital signs can be controlled from an external Java application. The main contributions of this work are: (a) outline and evaluation of the three-level VRML/Java implementation of the dynamic virtual environment, (b) proposal for a modified VRML Timesensor node, which greatly improves the overall control of system performance, and (c) architecture of the prototype distributed virtual environment for training in neonatal resuscitation comprising the interactive virtual newborn, active bedside monitor for vital signs and full 3D representation of the surgery room.

Education, Medical↗

A case study in pathway knowledgebase verification.

BACKGROUND: Biological databases and pathway knowledge-bases are proliferating rapidly. We are developing software tools for computer-aided hypothesis design and evaluation, and we would like our tools to take advantage of the information stored in these repositories. But before we can reliably use a pathway knowledge-base as a data source, we need to proofread it to ensure that it can fully support computer-aided information integration and inference. RESULTS: We design a series of logical tests to detect potential problems we might encounter using a particular knowledge-base, the Reactome database, with a particular computer-aided hypothesis evaluation tool, HyBrow. We develop an explicit formal language from the language implicit in the Reactome data format and specify a logic to evaluate models expressed using this language. We use the formalism of finite model theory in this work. We then use this logic to formulate tests for desirable properties (such as completeness, consistency, and well-formedness) for pathways stored in Reactome. We apply these tests to the publicly available Reactome releases (releases 10 through 14) and compare the results, which highlight Reactome's steady improvement in terms of decreasing inconsistencies. We also investigate and discuss Reactome's potential for supporting computer-aided inference tools. CONCLUSION: The case study described in this work demonstrates that it is possible to use our model theory based approach to identify problems one might encounter using a knowledge-base to support hypothesis evaluation tools. The methodology we use is general and is in no way restricted to the specific knowledge-base employed in this case study. Future application of this methodology will enable us to compare pathway resources with respect to the generic properties such resources will need to possess if they are to support automated reasoning.

Algorithms↗

PsyScript: a Macintosh application for scripting experiments.

PsyScript is a scriptable application allowing users to describe experiments in Apple's compiled high-level object-oriented AppleScript language, while still supporting millisecond or better within-trial event timing (delays can be in milliseconds or refresh-based, and PsyScript can wait on external I/O, such as eye movement fixations). Because AppleScript is object oriented and system-wide, PsyScript experiments support complex branching, code reuse, and integration with other applications. Included AppleScript-based libraries support file handling and stimulus randomization and sampling, as well as more specialized tasks, such as adaptive testing. Advanced features include support for the BBox serial port button box, as well as a low-cost USB-based digital I/O card for millisecond timing, recording of any number and types of responses within a trial, novel responses, such as graphics tablet drawing, and use of the Macintosh sound facilities to provide an accurate voice key, saving voice responses to disk, scriptable image creation, support for flicker-free animation, and gaze-dependent masking. The application is open source, allowing researchers to enhance the feature set and verify internal functions. Both the application and the source are available for free download at www.maccs.mq.edu.au/-tim/psyscript/.

Computer Graphics↗

The clinical display of radiologic information as an interactive multimedia report.

We regard the delivery of radiological information as an interactive multimedia report. We use a multimedia report model based on Extensible Markup Language (XML), rather than a traditional workstation model. Others have suggested a similar document-based approach. This display presentation includes image-related and text-based information and may contain interactive components (e.g., window, level and zoom). Using XML as a foundation for this multimedia presentation, we achieve flexibility and platform independence at a lower cost. XML allows for the separation of content and form. Content information, defined as elements (e.g., images, radiologic reports, and demographic information), is treated as independent information objects. The behavior of the elements can be changed for different users and tasks. In addition, by separating format detail from content, the appearance of the elements within the report can be modified. XML does not replace existing standards (i.e., Digital Imaging and Communications in Medicine [DICOM], Transmission Control Protocol/Internet Protocol [TCP/IP]). Instead, it provides a powerful framework that is used in combination with existing standards to allow system designers to modify display characteristics based on user need. We describe our application of XML to the clinical display of radiologic information.

Computer Systems↗

UML as a cell and biochemistry modeling language.

The systems biology community is building increasingly complex models and simulations of cells and other biological entities, and are beginning to look at alternatives to traditional representations such as those provided by ordinary differential equations (ODE). The lessons learned over the years by the software development community in designing and building increasingly complex telecommunication and other commercial real-time reactive systems, can be advantageously applied to the problems of modeling in the biology domain. Making use of the object-oriented (OO) paradigm, the unified modeling language (UML) and Real-Time Object-Oriented Modeling (ROOM) visual formalisms, and the Rational Rose RealTime (RRT) visual modeling tool, we describe a multi-step process we have used to construct top-down models of cells and cell aggregates. The simple example model described in this paper includes membranes with lipid bilayers, multiple compartments including a variable number of mitochondria, substrate molecules, enzymes with reaction rules, and metabolic pathways. We demonstrate the relevance of abstraction, reuse, objects, classes, component and inheritance hierarchies, multiplicity, visual modeling, and other current software development best practices. We show how it is possible to start with a direct diagrammatic representation of a biological structure such as a cell, using terminology familiar to biologists, and by following a process of gradually adding more and more detail, arrive at a system with structure and behavior of arbitrary complexity that can run and be observed on a computer. We discuss our CellAK (Cell Assembly Kit) approach in terms of features found in SBML, CellML, E-CELL, Gepasi, Jarnac, StochSim, Virtual Cell, and membrane computing systems.

Algorithms↗

What Digital Imaging and Communication in Medicine (DICOM) could look like in common object request broker (CORBA) and extensible markup language (XML).

Common object request broker architecture (CORBA) is a method for invoking distributed objects across a network. There has been some activity in applying this software technology to Digital Imaging and Communications in Medicine (DICOM), but no documented demonstration of how this would actually work. We report a CORBA demonstration that is functionally equivalent and in some ways superior to the DICOM communication protocol. In addition, in and outside of medicine, there is great interest in the use of extensible markup language (XML) to provide interoperation between databases. An example implementation of the DICOM data structure in XML will also be demonstrated. Using Visibroker ORB from Inprise (Scotts Valley, CA), a test bed was developed to simulate the principle DICOM operations: store, query, and retrieve (SQR). SQR is the most common interaction between a modality device application entity (AE) such as a computed tomography (CT) scanner, and a storage component, as well as between a storage component and a workstation. The storage of a CT study by invoking one of several storage objects residing on a network was simulated and demonstrated. In addition, XML database descriptors were used to facilitate the transfer of DICOM header information between independent databases. CORBA is demonstrated to have great potential for the next version of DICOM. It can provide redundant protection against single points of failure. XML appears to be an excellent method of providing interaction between separate databases managing the DICOM information object model, and may therefore eliminate the common use of proprietary client-server databases in commercial implementations of picture archiving and communication systems (PACS).

Computer Communication Networks↗

OILing the way to machine understandable bioinformatics resources.

The complex questions and analyses posed by biologists, as well as the diverse data resources they develop, require the fusion of evidence from different, independently developed, and heterogeneous resources. The web, as an enabler for interoperability, has been an excellent mechanism for data publication and transportation. Successful exchange and integration of information, however, depends on a shared language for communication (a terminology) and a shared understanding of what the data means (an ontology). Without this kind of understanding, semantic heterogeneity remains a problem for both humans and machines. One means of dealing with heterogeneity in bioinformatics resources is through terminology founded upon an ontology. Bioinformatics resources tend to be rich in human readable and understandable annotation, with each resource using its own terminology. These resources are machine readable, but not machine understandable. Ontologies have a role in increasing this machine understanding, reducing the semantic heterogeneity between resources and thus promoting the flexible and reliable interoperation of bioinformatics resources. This paper describes a solution derived from the semantic web [a machine understandable world-wide web (WWW)], the ontology inference layer (OIL), as a solution for semantic bioinformatics resources. The nature of the heterogeneity problems are presented along with a description of how metadata from domain ontologies can be used to alleviate this problem. A companion paper in this issue gives an example of the development of a bio-ontology using OIL.

Algorithms↗

Computerized system for posturographic research based on the ADAPT language for analysis of analogue signals.

A description is given of a system for posture analysis based on a specialized language ADAPT for analysis of analogue data, guaranteeing: 1. Analogue-to-digital conversion of the input signals with dialogue determination of the conversion parameters and monitoring of the signals on the screen. 2. Storage of the data on a diskette in a format guaranteeing high density of the data and fast exchange with the computer. 3. Calculation of the following parameters of the stabilogram and statokinesigram separately for open and for closed eyes: a) Anterior-posterior and lateral components of the path of the projection of the force centre SPAP and SPLAT; b) Mean frequency of the sways: fAP and fLAT; c) Ratio between the anterior-posterior and the lateral sways: AP/LAT. d) Surface A covered by the shifting of the centre of force; e) The path (SP) of the centre of application of the force; f) Mean amplitude (MA) of the sways for one second; g) Mean frequency (MF) of the sways. Romberg's coefficients are calculated for all parameters. 4. High speed of the calculations. 5. Graphic and digital display of all results on the screen from where they can be transferred to a printer, if necessary.

Computer Systems↗

What is mzXML good for?

mzXML (extensible markup language) is one of the pioneering data formats for mass spectrometry-based proteomics data collection. It is an open data format that has benefited and evolved as a result of the input of many groups, and it continues to evolve. Due to its dynamic history, its structure, purpose and applicability have all changed with time, meaning that groups that have looked at the standard at different points during its evolution have differing impressions of the usefulness of mzXML. In discussing mzXML, it is important to understand what mzXML is not. First, mzXML does not capture the raw data. Second, mzXML is not sufficient for regulatory submission. Third, mzXML is not optimized for computation and, finally, mzXML does not capture the experiment design. In general, it is the authors' opinion that XML is not a panacea for bioinformatics or a substitute for good data representation, and groups that want to use mzXML (or other XML-based representations) directly for data storage or computation will encounter performance and scalability problems. With these limitations in mind, the authors conclude that mzXML is, nonetheless, an indispensable data exchange format for proteomics.

Computational Biology↗

A general XML schema and SPM toolbox for storage of neuro-imaging results and anatomical labels.

With the increased frequency of multisite, large-scale collaborative neuro-imaging studies, the need for a general, self-documenting framework for the storage and retrieval of activation maps and anatomical labels becomes evident. To address this need, we have developed and extensible markup language (XML) schema and associated tools for the storage of neuro-imaging activation maps and anatomical labels. This schema, as part of the XML-based Clinical Experiment Data Exchange (XCEDE) schema, provides storage capabilities for analysis annotations, activation threshold parameters, and cluster and voxel-level statistics. Activation parameters contain information describing the threshold, degrees of freedom, FWHM smoothness, search volumes, voxel sizes, expected voxels per cluster, and expected number of clusters in the statistical map. Cluster and voxel statistics can be stored along with the coordinates, threshold, and anatomical label information. Multiple threshold types can be documented for a given cluster or voxel along with the uncorrected and corrected probability values. Multiple atlases can be used to generate anatomical labels and stored for each significant voxel or cluter. Additionally, a toolbox for Statistical Parametric Mapping software (http://www. fil. ion.ucl.ac.uk/spm/) was created to capture the results from activation maps using the XML schema that supports both SPM99 and SPM2 versions (http://nbirn.net/Resources/Users/ Applications/xcede/SPM_XMLTools.htm). Support for anatomical labeling is available via the Talairach Daemon (http://ric.uthscsa. edu/projects/talairachdaemon.html) and Automated Anatomical Labeling (http://www. cyceron.fr/freeware/).

Animals↗

Relating UMLS semantic types and task-based ontology to computer-interpretable clinical practice guidelines.

Medical knowledge in clinical practice guideline (GL) texts is the source of task-based computer-interpretable clinical guideline models (CIGMs). We have used Unified Medical Language System (UMLS) semantic types (STs) to understand the percentage of GL text which belongs to a particular ST. We also use UMLS semantic network together with the CIGM-specific ontology to derive a semantic meaning behind the GL text. In order to achieve this objective, we took nine GL texts from the National Guideline Clearinghouse (NGC) and marked up the text dealing with a particular ST. The STs we took into consideration were restricted taking into account the requirements of a task-based CIGM. We used DARPA Agent Markup Language and Ontology Inference Layer (DAML + OIL) to create the UMLS and CIGM specific semantic network. For the latter, as a bench test, we used the 1999 WHO-International Society of Hypertension Guidelines for the Management of Hypertension. We took into consideration the UMLS STs closest to the clinical tasks. The percentage of the GL text dealing with the ST "Health Care Activity" and subtypes "Laboratory Procedure", "Diagnostic Procedure" and "Therapeutic or Preventive Procedure" were measured. The parts of text belonging to other STs or comments were separated. A mapping of terms belonging to other STs was done to the STs under "HCA" for representation in DAML + OIL. As a result, we found that the three STs under "HCA" were the predominant STs present in the GL text. In cases where the terms of related STs existed, they were mapped into one of the three STs. The DAML + OIL representation was able to describe the hierarchy in task-based CIGMs. To conclude, we understood that the three STs could be used to represent the semantic network of the task-bases CIGMs. We identified some mapping operators which could be used for the mapping of other STs into these.

Humans↗