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Knowledge-based analysis of microarray gene expression data by using support vector machines.

We introduce a method of functionally classifying genes by using gene expression data from DNA microarray hybridization experiments. The method is based on the theory of support vector machines (SVMs). SVMs are considered a supervised computer learning method because they exploit prior knowledge of gene function to identify unknown genes of similar function from expression data. SVMs avoid several problems associated with unsupervised clustering methods, such as hierarchical clustering and self-organizing maps. SVMs have many mathematical features that make them attractive for gene expression analysis, including their flexibility in choosing a similarity function, sparseness of solution when dealing with large data sets, the ability to handle large feature spaces, and the ability to identify outliers. We test several SVMs that use different similarity metrics, as well as some other supervised learning methods, and find that the SVMs best identify sets of genes with a common function using expression data. Finally, we use SVMs to predict functional roles for uncharacterized yeast ORFs based on their expression data.

Algorithms↗

A knowledge-based weighting approach to ligand-based virtual screening.

On the basis of the recently introduced reduced graph concept of ErG (extending reduced graphs), a straightforward weighting approach to include additional (e.g., structural or SAR) knowledge into similarity searching procedures for virtual screening (wErG) is proposed. This simple procedure is exemplified with three data sets, for which interaction patterns available from X-ray structures of native or peptidomimetic ligands with their target protein are used to significantly improve retrieval rates of known actives from the MDL Drug Report database. The results are compared to those of other virtual screening techniques such as Daylight fingerprints, FTrees, UNITY, and various FlexX docking protocols. Here, it is shown that wErG exhibits a very good and stable performance independent of the target structure. On the basis of this (and the fact that ErG retrieves structurally more dissimilar compounds due to its potential to perform scaffold-hopping), the combination of wErG and FlexX is successfully explored. Overall, wErG is not only an easily applicable weighting procedure that efficiently identifies actives in large data sets but it is also straightforward to understand for both medicinal and computational chemists and can, therefore, be driven by several aspects of project-related knowledge (e.g., X-ray, NMR, SAR, and site-directed mutagenesis) in a very early stage of the hit identification process.

Computational Biology↗

Knowledge-based classification of neuronal fibers in entire brain.

This work presents a framework driven by parcellation of brain gray matter in standard normalized space to classify the neuronal fibers obtained from diffusion tensor imaging (DTI) in entire human brain. Classification of fiber bundles into groups is an important step for the interpretation of DTI data in terms of functional correlates of white matter structures. Connections between anatomically delineated brain regions that are considered to form functional units, such as a short-term memory network, are identified by first clustering fibers based on their terminations in anatomically defined zones of gray matter according to Talairach Atlas, and then refining these groups based on geometric similarity criteria. Fiber groups identified this way can then be interpreted in terms of their functional properties using knowledge of functional neuroanatomy of individual brain regions specified in standard anatomical space, as provided by functional neuroimaging and brain lesion studies.

Algorithms↗

A hybrid knowledge based system for therapy adjustment in gestational diabetes.

This poster describes a system to analyze self-monitoring data of gestational diabetic patients, for obtaining an assessment of their metabolic control with the final goal of supporting decision-making in therapy adjustment. The system is able to manage incomplete data and to make temporal reasoning under uncertainty, the two most important constraints when analyzing ambulatory monitoring data. Two different formalism have been used to represent and manage the knowledge: a dynamic Bayesian network and a production system based on rules. The outcomes provided by the whole system are: information on possible patient transgressions of the prescribed treatment and recommendations of treatment adjustments.

Artificial Intelligence↗

Predictive microbiology: providing a knowledge-based framework for change management.

This contribution considers predictive microbiology in the context of the Food Micro 2002 theme, "Microbial adaptation to changing environments". To provide a reference point, the state of food microbiology knowledge in the mid-1970s is selected and from that time, the impact of social and demographic changes on microbial food safety is traced. A short chronology of the history of predictive microbiology provides context to discuss its relation to and interactions with hazard analysis critical control point (HACCP) and risk assessment. The need to take account of the implications of microbial adaptability and variable population responses is couched in terms of the dichotomy between classical versus quantal microbiology introduced by Bridson and Gould [Lett. Appl. Microbiol. 30 (2000) 95]. The role of population response patterns and models as guides to underlying physiological processes draws attention to the value of predictive models in development of novel methods of food preservation. It also draws attention to the paradox facing today's food industry that is required to balance the "clean, green" aspirations of consumers with the risk, to safety or shelf life, of removing traditional barriers to microbial development. This part of the discussion is dominated by consideration of models and responses that lead to stasis and inactivation of microbial populations. This highlights the consequence of change on predictive modelling where the need is now to develop interface and non-thermal death models to deal with pathogens that have low infective doses for general and/or susceptible populations in the context of minimal preservation treatments. The challenge is to demonstrate the validity of such models and to develop applications of benefit to the food industry and consumers as was achieved with growth models to predict shelf life and the hygienic equivalence of food processing operations.

Bacteria↗

PromAn: an integrated knowledge-based web server dedicated to promoter analysis.

PromAn is a modular web-based tool dedicated to promoter analysis that integrates distinct complementary databases, methods and programs. PromAn provides automatic analysis of a genomic region with minimal prior knowledge of the genomic sequence. Prediction programs and experimental databases are combined to locate the transcription start site (TSS) and the promoter region within a large genomic input sequence. Transcription factor binding sites (TFBSs) can be predicted using several public databases and user-defined motifs. Also, a phylogenetic footprinting strategy, combining multiple alignment of large genomic sequences and assignment of various scores reflecting the evolutionary selection pressure, allows for evaluation and ranking of TFBS predictions. PromAn results can be displayed in an interactive graphical user interface, PromAnGUI. It integrates all of this information to highlight active promoter regions, to identify among the huge number of TFBS predictions those which are the most likely to be potentially functional and to facilitate user refined analysis. Such an integrative approach is essential in the face of a growing number of tools dedicated to promoter analysis in order to propose hypotheses to direct further experimental validations. PromAn is publicly available at http://bips.u-strasbg.fr/PromAn.

Binding Sites↗

A gentle introduction to knowledge-based systems in medicine.

In summary, AI expert systems, through the example of medical problem solving, have been examined, considering goals, problems addressed, and problems resolved (or not resolved). How these systems attempt to replicate the knowledge and strategies of human experts has been shown, as well as how they determine these factors (in the form of the protocol). Through the example of diagnosis, some of the types of knowledge and approaches such systems must encode have been illustrated. Concrete examples of approaches to encoding were presented using MYCIN and PIP. These systems demonstrate more clearly the complexity of the problem domains under consideration, how that complexity can be dealt with, and the limitations and potential of AI. It is apparent that such systems have unique contributions to make, not only in terms of straightforward usefulness but also in terms of inspectability, which may be extended to a capacity for "explaining." On a more basic level, they are generating a reexamination of what is considered "intelligent" behavior--which may itself lead to future concepts, systems, and tools. Moreover, the fundamental goal of generality in the design of AI systems makes such things as, for example, the hypothetico-deductive model of behavior transferrable across domains, conferring a similar ability for revitalization and reexamination in each one.

Clinical Protocols↗

[A knowledge-based method for 3D segmentation and display of human brain].

From the view of the artificial intelligence, a new method of segmentation and display of human brain medical images is descrided. On the basis of the knowledge of brain anatomy and image processing, we have built the 3D knowledge mobel using frame as the main knowledge expression method. Under the guide of the knowledge, the main structures in the brain are segmented and displayed by means of the "inelligent ray-tracing".

Artificial Intelligence↗

KBSIM: a system for interactive knowledge-based simulation.

The KBSIM system integrates quantitative simulation with symbolic reasoning techniques, under the control of a user interface management system, using a relational database management system for data storage and interprocess communication. The system stores and processes knowledge from three distinct knowledge domains, viz. (i) knowledge about the processes of the system under investigation, expressed in terms of a Continuous System Simulation Language (CSSL); (ii) heuristic knowledge on how to reach the goals of the simulation experiment, expressed in terms of a Rule Description Language (RDL); and (iii) knowledge about the requirements of the intended users, expressed in terms of a User Interface Description Language (UIDL). The user works in an interactive environment controlling the simulation course with use of a mouse and a large screen containing a set of 'live' charts and forms. The user is assisted by an embedded 'expert system' module continuously watching both the system's behavior and the user's action, and producing alerts, alarms, comments and advice. The system was developed on a Hewlett-Packard 9000/350 workstation under the HP-Unix and HP-Windows operating systems, using the MIMER database management system, and Fortran, Prolog/Lisp and C as implementation languages. The KBSIM system has great potentials for supporting problem solving, design of working procedures and teaching related to management of highly dynamic systems.

Artificial Intelligence↗

The impact of a cancer education program on the knowledge base of participating students.

BACKGROUND: Partners in Research is a ten-week summer elective designed to provide cancer-related educational activities. This study was undertaken to evaluate the impact of the program on the general cancer knowledge of medical students, pharmacy students, and undergraduate biology majors. METHODS: The 24 students enrolled in 1999 were evaluated using a pretest and post-test with 75 multiple-choice questions. RESULTS: The mean test score increased significantly from 46.6% to 53.0% (p = 0.001). Improvements were significant for general cancer knowledge and three specific disease categories (breast, gastrointestinal, and skin cancers). CONCLUSIONS: The results indicate that the program does increase the cancer-related knowledge of students.

Clinical Competence↗

Exploring the relationship between rationality and bounded rationality in medical knowledge-based systems.

If our goal in Artificial Intelligence in Medicine (AIM) is to engineer systems health-care providers will both use and, in the process, improve their performance, we must concentrate on the development of causal theories of knowledge and problem solving. One broad direction in pursuing this goal is understanding the relationships between existing models of rationality and bounded rationality for similar tasks. Models of rationality refer to those approaches in which the optimal properties of the models are deductively provable, i.e. in which the processing is rational. Representative models of rationality used in AIM are deductive logical models, statistical models such as Bayesian inference models, and decision-analytic models. Models of bounded rationality are those which do not guarantee such optimal properties nor yield to deductive correctness proofs. These models have their roots in cognitive psychology. In this article we show how explicating the relationship between models of rationality and bounded rationality might be done in the case of abductive tasks in medicine. This is done by positioning these modeling approaches within the same framework (an abstract computational model) and interpreting in this context both computational complexity results concerning the nature of the task and empirical results studies of human problem-solving behavior.

Artificial Intelligence↗

Cerebellum segmentation employing texture properties and knowledge based image processing: applied to normal adult controls and patients.

A semi-automated method is described for segmenting the cerebellum from T(1)-weighted 3-dimensional magnetic resonance imaging scans of adult controls and patients. The method relies on prior knowledge involving a user-defined template as a guide to aid the segmentation of the cerebellum. As the gray and white matter intensity distribution in the cerebellum has a complex pattern, texture information that identified the "graininess" was employed to capture the intensity distribution of voxels. The textural information was used to group voxels in a small circular structuring element as belonging to the cerebellum region. The cerebella from scans of 15 of the 20 subjects were segmented both manually and using the semi-automated procedure; the results were strongly correlated (r = 0.985, n = 15, p < 0.0001), and the volumes obtained from the two methods differed by 2.3%. The cerebellar volumes in 10 normal subjects and 10 age- and sex-matched patients with a neuropsychiatric disorder (schizophrenia) did not differ significantly (p = 0.18). The whole cerebellum was segmented in approximately 30 min using the semi-automated procedure. The method described is robust, easy-to-use, fairly fast and gives objective measurements.

Cerebellum↗

Reducing discriminatory attitudes toward people living with HIV/AIDS (PLWHA) in Hong Kong: an intervention study using an integrated knowledge-based PLWHA participation and cognitive approach.

The present paper describes the development and evaluation of an intervention programme aiming to reduce adolescents' discriminatory attitudes toward people living with HIV/AIDS (PLWHA). The intervention programme integrates components of 'virtual interaction' with PLWHA (watching a documentary), knowledge enhancement and a simple cognitive exercise. To evaluate its effectiveness, the programme was implemented to about 600 form 3-4 (grade 9-10) students of three secondary schools in Hong Kong. Using a structured questionnaire, the level of discriminatory attitudes toward PLWHA, knowledge about HIV/AIDS and perceptions about PLWHA, etc. were measured before and after the implementation of the programme. A notable improvement on the level of acceptance of PLWHA and knowledge about HIV/AIDS was found after the implementation of the programme. Negative perceptions about PLWHA also reduced substantially. For instance, before the programme, over one-third (35.7%) of all respondents believed that the majority of PLWHA were promiscuous; the figure dropped to 15.8% after exposure to the programme (adjusted odds ratio = 0.35, p < 0.001). Further, some gender differences were observed. Female respondents tended to be less discriminatory toward PLWHA and responded more favourably to the programme than their male counterparts.

Acquired Immunodeficiency Syndrome↗

A consensus approach to maintain a knowledge based system in pathology.

The IDEM (Images and Diagnosis from Example in Medicine) software is a computerized environment able to store unambiguous descriptions of histopathologic images from pathologists. Medical imaging could benefit from such environments if they can easily and continuously be maintained. Within the IDEM environment, we developed a knowledge management module coupled with a consensus module to support knowledge acquisition and maintenance by the experts of the domain. Two pathologists, a senior and junior pathologist, reviewed fifty-three cases of breast pathology. Our findings indicate 1) that the IDEM knowledge management module allows experts to describe images by selecting terms and defining new ones if necessary, allowing the construction of a glossary for the domain and 2) that the consensus module, developed to store valid multi-experts cases, contributes also to validate new terms of the glossary and to refine semantic distance between terms. Such methodology could be applied to others highly evolving medical domains.

Artificial Intelligence↗

Prior-knowledge-based feedforward network simulation of true boiling point curve of crude oil.

Theoretical results and practical experience indicate that feedforward networks can approximate a wide class of functional relationships very well. This property is exploited in modeling chemical processes. Given finite and noisy training data, it is important to encode the prior knowledge in neural networks to improve the fit precision and the prediction ability of the model. In this paper, as to the three-layer feedforward networks and the monotonic constraint, the unconstrained method, Joerding's penalty function method, the interpolation method, and the constrained optimization method are analyzed first. Then two novel methods, the exponential weight method and the adaptive method, are proposed. These methods are applied in simulating the true boiling point curve of a crude oil with the condition of increasing monotonicity. The simulation experimental results show that the network models trained by the novel methods are good at approximating the actual process. Finally, all these methods are discussed and compared with each other.

Journal Article↗