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Gradient directed regularization for sparse Gaussian concentration graphs, with applications to inference of genetic networks.

Large-scale microarray gene expression data provide the possibility of constructing genetic networks or biological pathways. Gaussian graphical models have been suggested to provide an effective method for constructing such genetic networks. However, most of the available methods for constructing Gaussian graphs do not account for the sparsity of the networks and are computationally more demanding or infeasible, especially in the settings of high dimension and low sample size. We introduce a threshold gradient descent (TGD) regularization procedure for estimating the sparse precision matrix in the setting of Gaussian graphical models and demonstrate its application to identifying genetic networks. Such a procedure is computationally feasible and can easily incorporate prior biological knowledge about the network structure. Simulation results indicate that the proposed method yields a better estimate of the precision matrix than the procedures that fail to account for the sparsity of the graphs. We also present the results on inference of a gene network for isoprenoid biosynthesis in Arabidopsis thaliana. These results demonstrate that the proposed procedure can indeed identify biologically meaningful genetic networks based on microarray gene expression data.

Arabidopsis↗

Using neural network predicted secondary structure information in automatic protein NMR assignment.

In CAPRI, an automated NMR assignment software package that was developed in our laboratory, both chemical shift values and coupling topologies of spin patterns are used in a procedure for amino acids recognition. By using a knowledge base of chemical shift distributions of the 20 amino acid types, fuzzy mathematics, and pattern recognition theory, the spin coupling topological graphs are mapped onto specific amino acid residues. In this work, we investigated the feasibility of using secondary structure information of proteins as predicted by neural networks in the automated NMR assignment. As the 1H and 13C chemical shifts of proteins are known to correlate to their secondary structures, secondary structure information is useful in improving the amino acid recognition. In this study, the secondary structures of proteins predicted by the PHD protein server and our own trained neural networks are used in the amino acid type recognition. The results show that the predicted secondary structure information can help to improve the accuracy of the amino acid recognition.

Algorithms↗

Conceptual integration of information databases into an Intranet.

Large information systems handle massive volume of data stored in heterogeneous sources of information. Each server has its own model of concepts representation with regard to its aims. One of the main problems encountered by end-users when accessing different servers is to match their own viewpoint on biomedical concepts with their various representations that are made in the database servers. The aim of the project ARIANE is to provide end-users with easy-to-use and natural means to access and query heterogeneous information databases. The objectives of this research work consist in building a conceptual interface by means of the Internet technology inside an enterprise Intranet, and to propose a method to realize it. Moreover, this method provides designers of web sites with a powerful tool to manage them on the basis of an ontology of the biomedical domain. This method is based on the knowledge sources provided by the Unified Medical Language System project of the U.S. National Library of Medicine and exploits intensively the conceptual graphs theory.

Computer Communication Networks↗

[Carl Heinrich Stratz (1858 to 1924), one of the first researchers in growth and development--chronological tables of his life and work (author's transl)].

Review of education, life and work of C.H. Stratz. First a clinical gynecologist and always earning his living from this profession, he was interested in the problems of somatic and regional anthropology. After 1900 he became more and more engaged in observations of the child's development from the new-born to the adolescent. His publications, especially his graphs and pictures of morphological changes in the childs body and the signs of puberty, have the following years deeply influenced our knowledge on "orthology" within the medical problems of youth.

Anthropology, Physical↗

The project ARIANE: conceptual queries to information databases.

As information databases we consider all the collections of data records indexed by key-words, stored and delivered by computer systems. In previous research works we demonstrated the interest to design a conceptual model, in the conceptual graphs formalism, and to implement a computational model for information retrieval in large information databases. These models are based on the UMLS knowledge sources. This paper reminds briefly these models and describes tests done in querying a patients database and a bibliographical database.

Databases, Bibliographic↗

Building and using a medical ontology for knowledge management and cooperative work in a health care network.

In the context of a health care network, we describe our method for reconstitution of a medical ontology via the translation of a medical database (DB) towards RDF(S) language. Then we show how we extended this ontology among others through natural language processing of a textual corpus. Then, we present the construction of a tool called "Virtual Staff", enabling a cooperative diagnosis by some of the health care network actors, by relying on this medical ontology and on the creation of SOAP and QOC graphs.

Algorithms↗

Improving quality and performance practices using fiberoptic endoscopes in perioperative areas: a case study.

In response to the impact of healthcare reform, a re-engineering of problem areas within the University of Maryland's Medical System needed to be initiated. A critical issue to be addressed, within the perioperative areas of the hospital, was the delay in service because of the unavailability of functional fiberoptic endoscopes. This resulted in spiraling operating costs and compromised quality of care of patients. Analysis of the situation using fiberscope inventory data revealed unreliable quality-controlled reprocessing systems and lack of knowledge by the staff in handling and caring for the fiberscopes. A number of actions were taken to improve staff patterns of performance. Graphs, spreadsheets, and diagrams were used to pinpoint the problem areas for each perioperative area and were presented to the staff. These data were up-dated monthly to inform staff and inspire further improvements in performance. This re-engineering of the fiberoptic scope delivery system resulted in economic, operational, customers, and quality of care benefits. Fiberoptic endoscopes are increasingly used is surgical fields outside of the traditional endoscopy unit. Endoscopic nurses need to share expertise to improve the quality of performance in all areas of the hospital where fiberoptic scopes are used.

Academic Medical Centers↗

Myocardial motion estimation in tagged MR sequences by using alphaMI-based non rigid registration.

Tagged Magnetic Resonance Imaging (MRI) is currently the reference MR modality for myocardial motion and strain analysis. NMI-based non rigid registration has proven to be an accurate method to retrieve cardiac deformation fields. The use of alphaMI permits higher dimensional features to be implemented in myocardial deformation estimation through image registration. This paper demonstrates that this is feasible with a set of Haar wavelet features of high dimension. While we do not demonstrate performance improvement for this set of features, there is no significant degradation as compared to implementing the registration method with the traditional NMI metric. We use Entropic Spanning Graphs (ESGs) to estimate the alphaMI of the wavelet feature vectors WFVs since this is not possible with histograms. To the best of our knowledge, this is the first time that ESGs are used for non rigid registration.

Algorithms↗

Mathematical tools in analytical mass spectrometry.

Over the last few decades, mass spectrometry has become a powerful tool for exploring various aspects of molecular processes occurring in biological systems. Such exploration is leading to a greater understanding of various complex life processes; unraveling these processes poses the greatest challenge to contemporary bioscience. With due respect to sample preparation, data analysis is rapidly becoming a major obstacle to the conversion of experimental knowledge into valid conclusions. It is interesting to note that many problems related to mass spectrometry can be solved using techniques from computer science, graph theory and discrete mathematics. The aim of this manuscript is to recollect several essays that demonstrate the power and the need to apply such skills to mass spectrometry data interpretation. Special attention is paid to situations where traditional chemical analysis reaches its limits but mathematical reasoning can still allow us to reach valid conclusions.

Journal Article↗

Artificial Intelligence for Natural Products Discovery and Development.

Natural products (NPs) remain a cornerstone of modern drug discovery, offering stereochemical complexity and diverse bioactivities that precisely modulate therapeutic targets, refined through billions of years of evolution. However, their research has long been hindered by inefficient, empirical workflows, high resource consumption, structural complexity, and the "multicomponent, multi-target" nature of their mechanisms. The exponential growth of genomic, metabolomic, and spectral data has overwhelmed conventional analytical methods, exposing critical bottlenecks in handling high-dimensional, heterogeneous datasets that exceed human interpretive capacity. Artificial intelligence (AI) is emerging as a transformative paradigm to address these challenges, integrating multi-omics and chemical data to shift NP research from fragmented empiricism toward mechanism-driven, precision-oriented development. By leveraging deep learning architectures- including graph neural networks, Transformers, and diffusion-based generative models-AI enables systematic decoding of NP biosynthesis, automated structure elucidation, rational target identification, knowledge extraction from vast unstructured scientific literature, and de novo molecular design. This review comprehensively surveys recent advances in AI applications across the full NP discovery and development pipeline, encompassing genome mining, structure-based and ligand-based virtual screening, multimodal structural characterization, lead optimization, and biosynthetic pathway engineering. We further examine the emerging roles of protein-centric, molecule- centric, and multimodal foundation models, as well as large language models, in bridging genotype-to-chemotype gaps and unlocking unstructured scientific knowledge. Finally, we discuss critical challenges including data scarcity, representational limitations for complex stereochemistry, physical plausibility in generative models, and the urgent need for experimental validation, while outlining future directions toward autonomous experimentation, closed-loop optimization, and human-AI collaborative discovery.

Artificial intelligence↗

IRMA--content-based image retrieval in medical applications.

The impact of content-based access to medical images is frequently reported but existing systems are designed for only a particular modality or context of diagnosis. Contrarily, our concept of image retrieval in medical applications (IRMA) aims at a general structure for semantic content analysis that is suitable for numerous applications in case-based reasoning or evidence-based medicine. Within IRMA, stepwise processing results in six layers of information modeling (raw data layer, registered data layer, feature layer, scheme layer, object layer, knowledge layer) incorporating medical expert knowledge. At the scheme layer, medical images are represented by a hierarchical structure of ellipses (blobs) describing image regions. Hence, image retrieval transforms to graph matching. The multilayer processing is implemented using a distributed system designed with only three core elements. The central database holds program sources, process-ing schemes, images, features, and blob trees; the scheduler balances distributed computing by addressing daemons running on all connected workstations; and the web server provides graphical user interfaces for data entry and retrieval..

Computer Graphics↗

Thermal conduction effects in human skin.

To determine the maximum permissible temperature any material may attain without causing pain or burn on contact with bare skin, over 2000 observations were made of pain threshold during contact with materials at elevated temperatures. Six materials were used representing the full range of thermal properties from good conductors to good insulators. Time to pain threshold was converted to time to threshold blister on the basis of the relationship between pain and burn established earlier for radiant and for convective heating. Calculated times to blister were used to predict the material temperatures causative of "touch-burn". Experimentally produced threshold blisters at the predicted temperature-times verified the predictions. Graphs and equations were generated for determining safe temperatures for any material in contact with bare skin for 1-5 s solely from a knowledge of its thermal properties. Conversely, the thermal inertia (k rho c) of the optimal material for a specific use and skin contact can be predicted from a knowledge of the maximum material temperature and length of contact time anticipated.

Aerospace Medicine↗

Proposed methodology for knowledge acquisition: a study on congenital heart disease diagnosis.

This paper proposes a methodology for knowledge acquisition (KA) from multiple experts, in an attempt to elicit the heuristic rules followed by the physician in diagnosing twelve frequently occurring congenital heart diseases (CHD). Twenty-two pediatric cardiologists and twenty-three general cardiologists were interviewed with this technique; 274 interviews were conducted, 169 with the 22 experts, 105 with the 23 non-experts. A graph formalism was employed to represent their reasoning model, leading to the construction of a "mean reasoning model" for each diagnosis, separately for experts and non-experts. The results indicate that experts, compared to non-experts, tend to build knowledge representation models (KRM) that are smaller and less complex. Qualitative differences in information utilization between the two groups were also observed. Entropy analysis suggests a greater objectivity and cohesion of the experts' model.

Algorithms↗

Model of interactions in biology and application to heterogeneous network in yeast.

A major challenge for bioinformatics and theoretical biology is to build and analyse a unified model of biological knowledge resulting from high-throughput experiment data. Former work analyzed heterogeneous data (protein-protein interactions, genetic regulation, metabolism, synexpression) by modelling them by graphs. These models are unable to represent the qualitative dynamics of the reactions or to model the n-ary interactions. Here, MIB, the Model of Interactions in Biology, a bipartite model of biological networks, is introduced, and its use for topological analysis of the heterogeneous network is presented. Heterogeneous loops and links between synexpression pattern and underlying molecular mechanisms are proposed.

Biology↗

An AI-based communication system for motor and speech disabled persons: design methodology and prototype testing.

An intelligent communication device is developed to assist the nonverbal, motor disabled in the generation of written and spoken messages. The device is centered on a knowledge base of the grammatical rules and message elements. A "belief" reasoning scheme based on both the information from external sources and the embedded knowledge is used to optimize the process of message search. The search for the message elements is conceptualized as a path search in the language graph, and a special frame architecture is used to construct and to partition the graph. Bayesian "belief" reasoning from the Dempster-Shafer theory of evidence is augmented to cope with time-varying evidence. An "information fusion" strategy is also introduced to integrate various forms of external information. Experimental testing of the prototype system is discussed.

Artificial Intelligence↗

The KEGG database.

KEGG (http://www.genome.ad.jp/kegg/) is a suite of databases and associated software for understanding and simulating higher-order functional behaviours of the cell or the organism from its genome information. First, KEGG computerizes data and knowledge on protein interaction networks (PATHWAY database) and chemical reactions (LIGAND database) that are responsible for various cellular processes. Second, KEGG attempts to reconstruct protein interaction networks for all organisms whose genomes are completely sequenced (GENES and SSDB databases). Third, KEGG can be utilized as reference knowledge for functional genomics (EXPRESSION database) and proteomics (BRITE database) experiments. I will review the current status of KEGG and report on new developments in graph representation and graph computations.

Amino Acid Sequence↗

[Automatic diagnosis of malignant degree of brain glioma based on Bayesian network].

Bayesian network connects graph theory with statistics, being an important research direction in data mining. Compared with other approaches used for data mining, Bayesian network can combine prior knowledge with observed data. Besides that, it can handle incomplete data sets. This paper applies Bayesian network to predict the malignant degree of brain glioma. Totally 280 cases are collected, and some of them contain missing values. Preprocessing is taken to make them applicable to the algorithms. Unlike MLP network, both Bayesian network and decision tree use attribute-value pairs to represent diagnostic knowledge derived from treated cases. These could improve both the understandability and applicability of their results. Results of all these algorithms can achieve accuracy rate over 80%, which satisfies the requirement of neuroradiologists.

Bayes Theorem↗

A model for medical knowledge representation application to the analysis of descriptive pathology reports.

A new knowledge-representation system is presented, designed for medical knowledge-based applications and in particular for the analysis of descriptive medical reports. Knowledge is represented at two levels. A definitional level uses a concept-type hierarchy, a relation-type hierarchy, and a set of schematic graphs to define the concepts used and the relations between them, as well as different types of cardinality restrictions on these relations. A set of compositional hierarchies using the classic "has-part" relation as well as a new set-inclusion relation allows concept composition to be precisely defined. An assertional level allows the creation and manipulation of empirical data, in the form of graphs using the concepts, relations, and constraints defined at the definition level. The use of cardinality constraints in graph unification is considered in the context of descriptive medical discourse analysis.

Artificial Intelligence↗