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Subpopulation-specific confidence designation for more informative biomedical classification.

ABSTRACT: Although classification algorithms are promising tools to support clinical diagnosis and treatment of disease, the usual implicit assumption underlying these algorithms, that all patients are homogeneous with respect to characteristics of interest, is unsatisfactory. The objective here is to exploit the population heterogeneity reflected by characteristics that may not be apparent and thus not controlled, in order to differentiate levels of classification accuracy between subpopulations and further the goal of tailoring therapies on an individual basis.A new subpopulation-based confidence approach is developed in the context of a selective voting algorithm defined by an ensemble of convex-hull classifiers. Populations of training samples are divided into three subpopulations that are internally homogeneous, with different levels of predictivity. Two different distance measures are used to cluster training samples into subpopulations and assign test samples to these subpopulations.Validation of the new approach's levels of confidence of classification is carried out using six publicly available datasets. Our approach demonstrates a positive correspondence between the predictivity designations derived from training samples and the classification accuracy of test samples. The average difference between highest- and lowest-confidence accuracies for the six datasets is 17.8%, with a minimum of 11.3% and a maximum of 24.1%.The classification accuracy increases as the designated confidence increases.

SUBMITTER: Zhang C

PROVIDER: S-EPMC3727244 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Subpopulation-specific confidence designation for more informative biomedical classification.

Zhang Chuanlei C Kodell Ralph L RL

Artificial intelligence in medicine 20130602 3

<h4>Objective</h4>Although classification algorithms are promising tools to support clinical diagnosis and treatment of disease, the usual implicit assumption underlying these algorithms, that all patients are homogeneous with respect to characteristics of interest, is unsatisfactory. The objective here is to exploit the population heterogeneity reflected by characteristics that may not be apparent and thus not controlled, in order to differentiate levels of classification accuracy between subpo ...[more]

PMID: 23731649

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Project description:BackgroundSupertree methods combine phylogenies with overlapping sets of taxa into a larger one. Topological conflicts frequently arise among source trees for methodological or biological reasons, such as long branch attraction, lateral gene transfers, gene duplication/loss or deep gene coalescence. When topological conflicts occur among source trees, liberal methods infer supertrees containing the most frequent alternative, while veto methods infer supertrees not contradicting any source tree, i.e. discard all conflicting resolutions. When the source trees host a significant number of topological conflicts or have a small taxon overlap, supertree methods of both kinds can propose poorly resolved, hence uninformative, supertrees.ResultsTo overcome this problem, we propose to infer non-plenary supertrees, i.e. supertrees that do not necessarily contain all the taxa present in the source trees, discarding those whose position greatly differs among source trees or for which insufficient information is provided. We detail a variant of the PhySIC veto method called PhySIC_IST that can infer non-plenary supertrees. PhySIC_IST aims at inferring supertrees that satisfy the same appealing theoretical properties as with PhySIC, while being as informative as possible under this constraint. The informativeness of a supertree is estimated using a variation of the CIC (Cladistic Information Content) criterion, that takes into account both the presence of multifurcations and the absence of some taxa. Additionally, we propose a statistical preprocessing step called STC (Source Trees Correction) to correct the source trees prior to the supertree inference. STC is a liberal step that removes the parts of each source tree that significantly conflict with other source trees. Combining STC with a veto method allows an explicit trade-off between veto and liberal approaches, tuned by a single parameter.Performing large-scale simulations, we observe that STC+PhySIC_IST infers much more informative supertrees than PhySIC, while preserving low type I error compared to the well-known MRP method. Two biological case studies on animals confirm that the STC preprocess successfully detects anomalies in the source trees while STC+PhySIC_IST provides well-resolved supertrees agreeing with current knowledge in systematics.ConclusionThe paper introduces and tests two new methodologies, PhySIC_IST and STC, that demonstrate the interest in inferring non-plenary supertrees as well as preprocessing the source trees. An implementation of the methods is available at: http://www.atgc-montpellier.fr/physic_ist/.

Project description:Mining disease-specific associations from existing knowledge resources can be useful for building disease-specific ontologies and supporting knowledge-based applications. Many association mining techniques have been exploited. However, the challenge remains when those extracted associations contained much noise. It is unreliable to determine the relevance of the association by simply setting up arbitrary cut-off points on multiple scores of relevance; and it would be expensive to ask human experts to manually review a large number of associations. We propose that machine-learning-based classification can be used to separate the signal from the noise, and to provide a feasible approach to create and maintain disease-specific vocabularies.We initially focused on disease-medication associations for the purpose of simplicity. For a disease of interest, we extracted potentially treatment-related drug concepts from biomedical literature citations and from a local clinical data repository. Each concept was associated with multiple measures of relevance (i.e., features) such as frequency of occurrence. For the machine purpose of learning, we formed nine datasets for three diseases with each disease having two single-source datasets and one from the combination of previous two datasets. All the datasets were labeled using existing reference standards. Thereafter, we conducted two experiments: (1) to test if adding features from the clinical data repository would improve the performance of classification achieved using features from the biomedical literature only, and (2) to determine if classifier(s) trained with known medication-disease data sets would be generalizable to new disease(s).Simple logistic regression and LogitBoost were two classifiers identified as the preferred models separately for the biomedical-literature datasets and combined datasets. The performance of the classification using combined features provided significant improvement beyond that using biomedical-literature features alone (p-value<0.001). The performance of the classifier built from known diseases to predict associated concepts for new diseases showed no significant difference from the performance of the classifier built and tested using the new disease's dataset.It is feasible to use classification approaches to automatically predict the relevance of a concept to a disease of interest. It is useful to combine features from disparate sources for the task of classification. Classifiers built from known diseases were generalizable to new diseases.

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Subpopulation-specific confidence designation for more informative biomedical classification.

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Subpopulation-specific confidence designation for more informative biomedical classification.

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