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Analyzing gene expression data for pediatric and adult cancer diagnosis using logic learning machine and standard supervised methods.

ABSTRACT: BACKGROUND:Logic Learning Machine (LLM) is an innovative method of supervised analysis capable of constructing models based on simple and intelligible rules. In this investigation the performance of LLM in classifying patients with cancer was evaluated using a set of eight publicly available gene expression databases for cancer diagnosis. LLM accuracy was assessed by summary ROC curve (sROC) analysis and estimated by the area under an sROC curve (sAUC). Its performance was compared in cross validation with that of standard supervised methods, namely: decision tree, artificial neural network, support vector machine (SVM) and k-nearest neighbor classifier. RESULTS:LLM showed an excellent accuracy (sAUC?=?0.99, 95%CI: 0.98-1.0) and outperformed any other method except SVM. CONCLUSIONS:LLM is a new powerful tool for the analysis of gene expression data for cancer diagnosis. Simple rules generated by LLM could contribute to a better understanding of cancer biology, potentially addressing therapeutic approaches.

SUBMITTER: Verda D

PROVIDER: S-EPMC6873393 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Analyzing gene expression data for pediatric and adult cancer diagnosis using logic learning machine and standard supervised methods.

Verda Damiano D Parodi Stefano S Ferrari Enrico E Muselli Marco M

BMC bioinformatics 20191122 Suppl 9

<h4>Background</h4>Logic Learning Machine (LLM) is an innovative method of supervised analysis capable of constructing models based on simple and intelligible rules. In this investigation the performance of LLM in classifying patients with cancer was evaluated using a set of eight publicly available gene expression databases for cancer diagnosis. LLM accuracy was assessed by summary ROC curve (sROC) analysis and estimated by the area under an sROC curve (sAUC). Its performance was compared in cr ...[more]

PMID: 31757200

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Project description:BackgroundViral-host protein-protein interaction plays a vital role in pathogenesis, since it defines viral infection of the host and regulation of the host proteins. Identification of key viral-host protein-protein interactions (PPIs) has great implication for therapeutics.MethodsIn this study, a systematic attempt has been made to predict viral-host PPIs by integrating different features, including domain-domain association, network topology and sequence information using viral-host PPIs from VirusMINT. The three well-known supervised machine learning methods, such as SVM, Naïve Bayes and Random Forest, which are commonly used in the prediction of PPIs, were employed to evaluate the performance measure based on five-fold cross validation techniques.ResultsOut of 44 descriptors, best features were found to be domain-domain association and methionine, serine and valine amino acid composition of viral proteins. In this study, SVM-based method achieved better sensitivity of 67% over Naïve Bayes (37.49%) and Random Forest (55.66%). However the specificity of Naïve Bayes was the highest (99.52%) as compared with SVM (74%) and Random Forest (89.08%). Overall, the SVM and Random Forest achieved accuracy of 71% and 72.41%, respectively. The proposed SVM-based method was evaluated on blind dataset and attained a sensitivity of 64%, specificity of 83%, and accuracy of 74%. In addition, unknown potential targets of hepatitis B virus-human and hepatitis E virus-human PPIs have been predicted through proposed SVM model and validated by gene ontology enrichment analysis. Our proposed model shows that, hepatitis B virus "C protein" binds to membrane docking protein, while "X protein" and "P protein" interacts with cell-killing and metabolic process proteins, respectively.ConclusionThe proposed method can predict large scale interspecies viral-human PPIs. The nature and function of unknown viral proteins (HBV and HEV), interacting partners of host protein were identified using optimised SVM model.

Project description:BackgroundGene regulatory network inference remains a challenging problem in systems biology despite the numerous approaches that have been proposed. When substantial knowledge on a gene regulatory network is already available, supervised network inference is appropriate. Such a method builds a binary classifier able to assign a class (Regulation/No regulation) to an ordered pair of genes. Once learnt, the pairwise classifier can be used to predict new regulations. In this work, we explore the framework of Markov Logic Networks (MLN) that combine features of probabilistic graphical models with the expressivity of first-order logic rules.ResultsWe propose to learn a Markov Logic network, e.g. a set of weighted rules that conclude on the predicate "regulates", starting from a known gene regulatory network involved in the switch proliferation/differentiation of keratinocyte cells, a set of experimental transcriptomic data and various descriptions of genes all encoded into first-order logic. As training data are unbalanced, we use asymmetric bagging to learn a set of MLNs. The prediction of a new regulation can then be obtained by averaging predictions of individual MLNs. As a side contribution, we propose three in silico tests to assess the performance of any pairwise classifier in various network inference tasks on real datasets. A first test consists of measuring the average performance on balanced edge prediction problem; a second one deals with the ability of the classifier, once enhanced by asymmetric bagging, to update a given network. Finally our main result concerns a third test that measures the ability of the method to predict regulations with a new set of genes. As expected, MLN, when provided with only numerical discretized gene expression data, does not perform as well as a pairwise SVM in terms of AUPR. However, when a more complete description of gene properties is provided by heterogeneous sources, MLN achieves the same performance as a black-box model such as a pairwise SVM while providing relevant insights on the predictions.ConclusionsThe numerical studies show that MLN achieves very good predictive performance while opening the door to some interpretability of the decisions. Besides the ability to suggest new regulations, such an approach allows to cross-validate experimental data with existing knowledge.

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Dataset Information

Analyzing gene expression data for pediatric and adult cancer diagnosis using logic learning machine and standard supervised methods.

Publications

Analyzing gene expression data for pediatric and adult cancer diagnosis using logic learning machine and standard supervised methods.

Similar Datasets

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