Coastal zone management in the fisheries sector program

International audienceThis paper presents an analysis of censored survival data for breast cancer specific mortality and disease-free survival. There are three stages to the process, namely time-to-event modelling, risk stratification by predicted outcome and model interpretation using rule extraction. Model selection was carried out using the benchmark linear model, Cox regression but risk staging was derived with Cox regression and with Partial Logistic Regression Artificial Neural Networks regularised with Automatic Relevance Determination (PLANN-ARD). This analysis compares the two approaches showing the benefit of using the neural network framework especially for patients at high risk. The neural network model also has results in a smooth model of the hazard without the need for limiting assumptions of proportionality. The model predictions were verified using out-of-sample testing with the mortality model also compared with two other prognostic models called TNG and the NPI rule model. Further verification was carried out by comparing marginal estimates of the predicted and actual cumulative hazards. It was also observed that doctors seem to treat mortality and disease-free models as equivalent, so a further analysis was performed to observe if this was the case. The analysis was extended with automatic rule generation using Orthogonal Search Rule Extraction (OSRE). This methodology translates analytical risk scores into the language of the clinical domain, enabling direct validation of the operation of the Cox or neural network model. This paper extends the existing OSRE methodology to data sets that include continuous-valued variables

How to find simple and accurate rules for viral protease cleavage specificities

<p>Abstract</p> <p>Background</p> <p>Proteases of human pathogens are becoming increasingly important drug targets, hence it is necessary to understand their substrate specificity and to interpret this knowledge in practically useful ways. New methods are being developed that produce large amounts of cleavage information for individual proteases and some have been applied to extract cleavage rules from data. However, the hitherto proposed methods for extracting rules have been neither easy to understand nor very accurate. To be practically useful, cleavage rules should be accurate, compact, and expressed in an easily understandable way.</p> <p>Results</p> <p>A new method is presented for producing cleavage rules for viral proteases with seemingly complex cleavage profiles. The method is based on orthogonal search-based rule extraction (OSRE) combined with spectral clustering. It is demonstrated on substrate data sets for human immunodeficiency virus type 1 (HIV-1) protease and hepatitis C (HCV) NS3/4A protease, showing excellent prediction performance for both HIV-1 cleavage and HCV NS3/4A cleavage, agreeing with observed HCV genotype differences. New cleavage rules (consensus sequences) are suggested for HIV-1 and HCV NS3/4A cleavages. The practical usability of the method is also demonstrated by using it to predict the location of an internal cleavage site in the HCV NS3 protease and to correct the location of a previously reported internal cleavage site in the HCV NS3 protease. The method is fast to converge and yields accurate rules, on par with previous results for HIV-1 protease and better than previous state-of-the-art for HCV NS3/4A protease. Moreover, the rules are fewer and simpler than previously obtained with rule extraction methods.</p> <p>Conclusion</p> <p>A rule extraction methodology by searching for multivariate low-order predicates yields results that significantly outperform existing rule bases on out-of-sample data, but are more transparent to expert users. The approach yields rules that are easy to use and useful for interpreting experimental data.</p

Efficient identification of independence networks using mutual information

Conditional independence graphs are now widely applied in science and industry to display interactions between large numbers of variables. However, the computational load of structure identification grows with the number of nodes in the network and the sample size. A tailored version of the PC algorithm is proposed which is based on mutual information tests with a specified testing order, combined with false negative reduction and false positive control. It is found to be competitive with current structure identification methodologies for both estimation accuracy and computational speed and outperforms these in large scale scenarios. The methodology is also shown to approximate dense networks. The comparisons are made on standard benchmarking data sets and an anonymized large scale real life example

Patient stratification with competing risks by multivariate Fisher distance

Early characterization of patients with respect to their predicted response to treatment is a fundamental step towards the delivery of effective, personalized care. Starting from the results of a time-to-event model with competing risks using the framework of partial logistic artificial neural networks with automatic relevance determination (PLANNCR-ARD), we discuss an effective semi-supervised approach to patient stratification with application to Acute Myeloid Leukaemia (AML) data (n = 509) acquired prospectively by the GIMEMA consortium. Multiple prognostic indices provided by the survival model are exploited to build a metric based on the Fisher information matrix. Cluster number estimation is then performed in the Fisher-induced affine space, yielding to the discovery of a stratification of the patients into groups characterized by significantly different mortality risks following induction therapy in AML. The proposed model is shown to be able to cluster the input data, while promoting specificity of both target outcomes, namely Complete Remission (CR) and Induction Death (ID). This generic clustering methodology generates an affine transformation of the data space that is coherent with the prognostic information predicted by the PLANNCR-ARD model

Different Methodologies for Patient Stratification Using Survival Data

Clinical characterization of breast cancer patients related to their risk and profiles is an important part for making their correct prognostic assessments. This paper first proposes a prognostic index obtained when it is applied a flexible non-linear time-to-event model and compares it to a widely used linear survival estimator. This index underpins different stratification methodologies including informed clustering utilising the principle of learning metrics, regression trees and recursive application of the log-rank test. Missing data issue was overcome using multiple imputation, which was applied to a neural network model of survival fitted to a data set for breast cancer (n=743). It was found the three methodologies broadly agree, having however important differences

A Clinical Decision Support System for Breast Cancer Patients

International audienceThis paper proposes a Web clinical decision support system for clinical oncologists and for breast cancer patients making prognostic assessments, using the particular characteristics of the individual patient. This system comprises three different prognostic modelling methodologies: the clinically widely used Nottingham prognostic index (NPI); the Cox regression modelling and a partial logistic artificial neural network with automatic relevance determination (PLANN-ARD). All three models yield a different prognostic index that can be analysed together in order to obtain a more accurate prognostic assessment of the patient. Missing data is incorporated in the mentioned models, a common issue in medical data that was overcome using multiple imputation techniques. Risk group assignments are also provided through a methodology based on regression trees, where Boolean rules can be obtained expressed with patient characteristics

p-Health in Breast Oncology: A Framework for Predictive and Participatory e-Systems

Maintaining the financial sustainability of healthcare provision makes developments in e-Systems of the utmost priority in healthcare. In particular, it leads to a radical review of healthcare delivery for the future as personalised, preventive, predictive and participatory, or p-Health. It is a vision that places e-Systems at the core of healthcare delivery, in contrast to current practice. This view of the demands of the 21st century sets an agenda that builds upon advances in engineering devices and computing infrastructure, but also computational intelligence and new models for communication between healthcare providers and the public. This paper gives an overview of p-Health with reference to decision support in breast cancer

Discovering hidden pathways in bioinformatics

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Discovering hidden pathways in bioinformatics

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