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Multiply sectioned Bayesian networks for neuromuscular diagnosis.

A prototype neuromuscular diagnostic system (PAINULIM) that diagnoses painful or impaired upper limbs has been developed based on Bayesian networks. This paper presents nonmathematically the major knowledge representation issues that arose in the development of PAINULIM. Motivated by the computational overhead of large application domains, and the desire to provide a user with an interface that gives a focused display of a subdomain of current interest, we built PAINULIM using the idea of multiply sectioned Bayesian networks. A preliminary evaluation of PAINULIM with 76 patients has demonstrated good clinical performance.

Artificial Intelligence↗

Advances to Bayesian network inference for generating causal networks from observational biological data.

MOTIVATION: Network inference algorithms are powerful computational tools for identifying putative causal interactions among variables from observational data. Bayesian network inference algorithms hold particular promise in that they can capture linear, non-linear, combinatorial, stochastic and other types of relationships among variables across multiple levels of biological organization. However, challenges remain when applying these algorithms to limited quantities of experimental data collected from biological systems. Here, we use a simulation approach to make advances in our dynamic Bayesian network (DBN) inference algorithm, especially in the context of limited quantities of biological data. RESULTS: We test a range of scoring metrics and search heuristics to find an effective algorithm configuration for evaluating our methodological advances. We also identify sampling intervals and levels of data discretization that allow the best recovery of the simulated networks. We develop a novel influence score for DBNs that attempts to estimate both the sign (activation or repression) and relative magnitude of interactions among variables. When faced with limited quantities of observational data, combining our influence score with moderate data interpolation reduces a significant portion of false positive interactions in the recovered networks. Together, our advances allow DBN inference algorithms to be more effective in recovering biological networks from experimentally collected data. AVAILABILITY: Source code and simulated data are available upon request. SUPPLEMENTARY INFORMATION: http://www.jarvislab.net/Bioinformatics/BNAdvances/

Algorithms↗

The role of Bayesian Networks in the diagnosis of pulmonary embolism.

Pulmonary embolism (PE) is a life-threatening condition and, despite advances in diagnostic technology, it remains an elusive diagnosis. The rich variety of possible clinical presentations make it particularly difficult to represent the diagnostic process as a 'decision tree'. However, Bayesian networks offer the opportunity of a compact representation of the domain underlying the decision process: once the network portrays the natural history of the disease, the utility of investigations can be quantitatively evaluated. We developed a network for the diagnosis of PE, including 72 variables to represent both the risk factors and the pathophysiological consequences of the disease. Its structure has been specified by discussing which causal relationships explain the manifestations of the disease. The quantitative measures of associations were retrieved from the medical literature, through a critical review of available studies and agreement on the assumptions made to cope with the lack of published information. Six examples are presented to illustrate the appropriateness of 'entropy reduction' as a measure of the utility of investigation, once the set of examinations to be evaluated is bounded on the grounds of their cost and the patient's current risk. The network, which has been given the acronym 'BayPAD' (Bayesian network for Pulmonary embolism Assisted Diagnosis), appears to be able to detect which observations make others irrelevant, so that decisions can be tailored to single cases.

Adult↗

Predicting survival in malignant skin melanoma using Bayesian networks automatically induced by genetic algorithms. An empirical comparison between different approaches.

In this work we introduce a methodology based on genetic algorithms for the automatic induction of Bayesian networks from a file containing cases and variables related to the problem. The structure is learned by applying three different methods: The Cooper and Herskovits metric for a general Bayesian network, the Markov blanket approach and the relaxed Markov blanket method. The methodologies are applied to the problem of predicting survival of people after 1, 3 and 5 years of being diagnosed as having malignant skin melanoma. The accuracy of the obtained models, measured in terms of the percentage of well-classified subjects, is compared to that obtained by the so-called Naive-Bayes. In the four approaches, the estimation of the model accuracy is obtained from the 10-fold cross-validation method.

Algorithms↗

Estimation of the hemodynamic response in event-related functional MRI: Bayesian networks as a framework for efficient Bayesian modeling and inference.

A convenient way to analyze blood-oxygen-level-dependent functional magnetic resonance imaging data consists of modeling the whole brain as a stationary, linear system characterized by its transfer function: the hemodynamic response function (HRF). HRF estimation, though of the greatest interest, is still under investigation, for the problem is ill-conditioned. In this paper, we recall the most general Bayesian model for HRF estimation and show how it can beneficially be translated in terms of Bayesian graphical models, leading to 1) a clear and efficient representation of all structural and functional relationships entailed by the model, and 2) a straightforward numerical scheme to approximate the joint posterior distribution, allowing for estimation of the HRF, as well as all other model parameters. We finally apply this novel technique on both simulations and real data.

Adolescent↗

Generating explanations and tutorial problems from Bayesian networks.

We present a system that generates explanations and tutorial problems from the probabilistic information contained in Bayesian belief networks. BANTER is a tool for high-level interaction with any Bayesian network whose nodes can be classified as hypotheses, observations, and diagnostic procedures. Users need no knowledge of Bayesian networks, only familiarity with the particular domain and an elementary understanding of probability. Users can query the knowledge base, identify optimal diagnostic procedures, and request explanations. We describe BANTER's algorithms and illustrate its application to an existing medical model.

Algorithms↗

Logistic regression and Bayesian networks to study outcomes using large data sets.

BACKGROUND: In nursing research, the interest in using large health care databases to predict nursing sensitive outcomes is growing rapidly. Traditionally, one of the most frequently used methods is logistic regression (LR), which, although powerful and familiar, has several limitations when used in the analysis of large databases. As a result, innovative approaches are required. APPROACH: To (a) introduce an innovative/alternative data analysis approach (Bayesian network), (b) discuss the constraints of LR and the complementary advantages of Bayesian networks (BNs) in working with large and multidimensional health care data, and (c) provide a fundamental understanding of the use of BNs in the nursing/health care domain. RESULTS: Studies have shown that BNs have several advantages over LR in analyzing complex and large data: (a) statistical assumptions, such as linearity and additivity, are relaxed; (b) handling of a larger number of predictors and identification of interactions among predictors is less complex; and (c) the discovery of structure, pattern, and knowledge, for example, of unknown, complex, and nonlinear relationships, in data is facilitated. CONCLUSION: Outcome studies, such as those undertaken by nurse researchers, may benefit from the examination and use of innovative approaches such as BNs to the analysis of very large and complex health care data sets.

Bayes Theorem↗

The evaluation of evidence in the forensic investigation of fire incidents (Part I): an approach using Bayesian networks.

The forensic investigation of the origin and cause of a fire incident is a particularly demanding area of expertise. As the available evidence is often incomplete or vague, uncertainty is a key element. The present study is an attempt to approach this through the use of Bayesian networks, which have been found useful in assisting human reasoning in a variety of disciplines in which uncertainty plays a central role. The present paper describes the construction of a Bayesian network (BN) and its use for drawing inferences about propositions of interest, based upon a single, possibly non replicable item of evidence: detected residual quantities of a flammable liquid in fire debris.

Journal Article↗

Comparison of statistical analysis and Bayesian Networks in the evaluation of dissolution performance of BCS Class II model drugs.

This project compared the effect of formulation variables on the dissolution performance of model Biopharmaceutics Classification System (BCS) Class II drugs from hard gelatin capsules using statistical analysis and Bayesian networks. The drugs chosen for this study were carbamazepine (CAR), chlorpropamide (CHL), diazepam (DIA), ketoprofen (KET), and naproxen (NAP). Formulations contained anhydrous lactose, microcrystalline cellulose, sodium stearyl fumerate, sodium lauryl sulfate, and croscarmellose sodium. A Box-Behnken experimental design was used in the statistical analysis. The weakly acidic drugs were tested using USP apparatus II with capsule sinkers in 0.1M pH 6.8 Potassium Phosphate buffer. The weakly basic drugs were tested using USP apparatus I in 0.1N HCl buffer. Mean dissolution profiles were compared via calculation of the similarity factor. The Box-Behnken experimental design was found to be useful in assessing primary and secondary excipient effects on dissolution. The Bayesian Network developed for the dataset mirrored the key excipient effects on dissolution performance.

Bayes Theorem↗

Growing Bayesian network models of gene networks from seed genes.

MOTIVATION: For the last few years, Bayesian networks (BNs) have received increasing attention from the computational biology community as models of gene networks, though learning them from gene-expression data is problematic. Most gene-expression databases contain measurements for thousands of genes, but the existing algorithms for learning BNs from data do not scale to such high-dimensional databases. This means that the user has to decide in advance which genes are included in the learning process, typically no more than a few hundreds, and which genes are excluded from it. This is not a trivial decision. We propose an alternative approach to overcome this problem. RESULTS: We propose a new algorithm for learning BN models of gene networks from gene-expression data. Our algorithm receives a seed gene S and a positive integer R from the user, and returns a BN for the genes that depend on S such that less than R other genes mediate the dependency. Our algorithm grows the BN, which initially only contains S, by repeating the following step R + 1 times and, then, pruning some genes; find the parents and children of all the genes in the BN and add them to it. Intuitively, our algorithm provides the user with a window of radius R around S to look at the BN model of a gene network without having to exclude any gene in advance. We prove that our algorithm is correct under the faithfulness assumption. We evaluate our algorithm on simulated and biological data (Rosetta compendium) with satisfactory results.

Algorithms↗

Using Bayesian networks in the construction of a bi-level multi-classifier. A case study using intensive care unit patients data.

Combining the predictions of a set of classifiers has shown to be an effective way to create composite classifiers that are more accurate than any of the component classifiers. There are many methods for combining the predictions given by component classifiers. We introduce a new method that combine a number of component classifiers using a Bayesian network as a classifier system given the component classifiers predictions. Component classifiers are standard machine learning classification algorithms, and the Bayesian network structure is learned using a genetic algorithm that searches for the structure that maximises the classification accuracy given the predictions of the component classifiers. Experimental results have been obtained on a datafile of cases containing information about ICU patients at Canary Islands University Hospital. The accuracy obtained using the presented new approach statistically improve those obtained using standard machine learning methods.

Algorithms↗

[Application of Bayesian network in syndrome differentiation system of traditional Chinese medicine].

The concept of syndrome in traditional Chinese medicine (TCM) is a nonlinear, open and complicated huge system. Syndrome differentiation in TCM belongs to cognitive and noetic science. To establish a new syndrome differentiation system based on the key elements of the syndrome is necessary for TCM practitioners to promote differentiation ability and reach consensus on differentiation method. With combination of experience and computation models, the Bayesian network was used in the study of the relationship between the key elements of syndrome and the symptoms, and the relationship among different key elements, in which the computing diagnosis result was identical to the result from an experienced TCM doctor. The study showed that Bayesian network is a good method to deal with the information of symptoms and signs for syndrome differentiation, but it is also not to reflect comprehensively the thinking ability of TCM doctors in doing syndrome differentiation.

Bayes Theorem↗

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.

Bayes Theorem↗

Pathways of urothelial cancer progression suggested by Bayesian network analysis of allelotyping data.

Urothelial cancers of the bladder (UC) comprise biologically heterogeneous group of tumors and display complex genetic alterations. Several genetic changes have been analyzed in detail and some of them are associated with the development and progression of UCs. Only a few studies, however, are focused on identifying the order in which the aberrations may appear during UC tumorigenesis. We have analyzed 123 papillary UCs of the bladder by microsatellites for each of the chromosomal regions that have been suggested to be specifically involved in this type of tumor. We used Bayesian network modeling that enables to uncover multivariate probabilistic dependencies between variables. This methodology applied to LOH data allowed us to discover patterns of losses in UCs. Exploiting the mechanism of probabilistic reasoning in Bayesian networks we suggest primary and secondary events in tumor pathogenesis and reconstruct the possible flow of progression of allelic changes. Losses of chromosome 9p and 9q were found to be the primary events. Losses of 8p and 17p are important events leading to progression of tumor cell clones. The loss of 17p occurs when both abnormalities of chromosome 9 and 8p are already present. There are chromosomal losses related to 8p (1q, 18q, 10q) and some losses like 5q/5p were associated with 17p, leading to the hypothesis of different genetic pathways of UC progression. The abnormalities of chromosome regions 13q, 16q, 6q, 14q, 3p are suggested to be late events being accumulated during the progression of cancer. Although some genetic changes were associated only with the 8p pathway, most secondary genetic changes appear in both pathways. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

Alleles↗

Combining wavelet analysis and Bayesian networks for the classification of auditory brainstem response.

The auditory brainstem response (ABR) has become a routine clinical tool for hearing and neurological assessment. In order to pick out the ABR from the background EEG activity that obscures it, stimulus-synchronized averaging of many repeated trials is necessary, typically requiring up to 2000 repetitions. This number of repetitions can be very difficult, time consuming and uncomfortable for some subjects. In this study, a method combining wavelet analysis and Bayesian networks is introduced to reduce the required number of repetitions, which could offer a great advantage in the clinical situation. 314 ABRs with 64 repetitions and 155 ABRs with 128 repetitions recorded from eight subjects are used here. A wavelet transform is applied to each of the ABRs, and the important features of the ABRs are extracted by thresholding and matching the wavelet coefficients. The significant wavelet coefficients that represent the extracted features of the ABRs are then used as the variables to build the Bayesian network for classification of the ABRs. In order to estimate the performance of this approach, stratified ten-fold cross-validation is used.

Algorithms↗

Computerized tongue diagnosis based on Bayesian networks.

Tongue diagnosis is an important diagnostic method in traditional Chinese medicine (TCM). However, due to its qualitative, subjective and experience-based nature, traditional tongue diagnosis has a very limited-application in clinical medicine. Moreover, traditional tongue diagnosis is always concerned with the identification of syndromes rather than with the connection between tongue abnormal appearances and diseases. This is not well understood in Western medicine, thus greatly obstruct its wider use in the world. In this paper, we present a novel computerized tongue inspection method aiming to address these problems. First, two kinds of quantitative features, chromatic and textural measures, are extracted from tongue images by using popular digital image processing techniques. Then, Bayesian networks are employed to model the relationship between these quantitative features and diseases. The effectiveness of the method is tested on a group of 455 patients affected by 13 common diseases as well as other 70 healthy volunteers, and the diagnostic results predicted by the previously trained Bayesian network classifiers are reported.

Artificial Intelligence↗

Prediction of splice sites with dependency graphs and their expanded bayesian networks.

MOTIVATION: Owing to the complete sequencing of human and many other genomes, huge amounts of DNA sequence data have been accumulated. In bioinformatics, an important issue is how to predict the complete structure of genes from the genomic DNA sequence, especially the human genome. A crucial part in the gene structure prediction is to determine the precise exon-intron boundaries, i.e. the splice sites, in the coding region. RESULTS: We have developed a dependency graph model to fully capture the intrinsic interdependency between base positions in a splice site. The establishment of dependency between two position is based on a chi2-test from known sample data. To facilitate statistical inference, we have expanded the dependency graph (which is usually a graph with cycles that make probabilistic reasoning very difficult, if not impossible) into a Bayesian network (which is a directed acyclic graph that facilitates statistical reasoning). When compared with the existing models such as weight matrix model, weight array model, maximal dependence decomposition, Cai et al.'s tree model as well as the less-studied second-order and third-order Markov chain models, the expanded Bayesian networks from our dependency graph models perform the best in nearly all the cases studied. AVAILABILITY: Software (a program called DGSplicer) and datasets used are available at http://csrl.ee.nthu.edu.tw/bioinf/ CONTACT: cclu@ee.nthu.edu.tw.

Bayes Theorem↗

A novel strategy for microarray quality control using Bayesian networks.

MOTIVATION: High-throughput microarray technologies enable measurements of the expression levels of thousands of genes in parallel. However, microarray printing, hybridization and washing may create substantial variability in the quality of the data. As erroneous measurements may have a drastic impact on the results by disturbing the normalization schemes and by introducing expression patterns that lead to incorrect conclusions, it is crucial to discard low quality observations in the early phases of a microarray experiment. A typical microarray experiment consists of tens of thousands of spots on a microarray, making manual extraction of poor quality spots impossible. Thus, there is a need for a reliable and general microarray spot quality control strategy. RESULTS: We suggest a novel strategy for spot quality control by using Bayesian networks, which contain many appealing properties in the spot quality control context. We illustrate how a non-linear least squares based Gaussian fitting procedure can be used in order to extract features for a spot on a microarray. The features we used in this study are: spot intensity, size of the spot, roundness of the spot, alignment error, background intensity, background noise, and bleeding. We conclude that Bayesian networks are a reliable and useful model for microarray spot quality assessment. SUPPLEMENTARY INFORMATION: http://sigwww.cs.tut.fi/TICSP/SpotQuality/.

Algorithms↗