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1.  Feature Selection in Computer-Aided Breast Cancer Diagnosis via Dynamic Contrast-Enhanced Magnetic Resonance Images 
Journal of Digital Imaging  2012;26(2):198-208.
The accuracy of computer-aided diagnosis (CAD) for early detection and classification of breast cancer in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is dependent upon the features used by the CAD classifier. Here, we show that fast orthogonal search (FOS), which provides a more efficient iterative manner of computing stepwise regression feature selection, can select features with predictive value from a set of kinetic and texture candidate features computed from dynamic contrast-enhanced magnetic resonance images. FOS can in minutes search candidate feature sets of millions of terms, which may include cross-products of features up to second-, third- or fourth-order. This method is tested on a set of 83 DCE-MRI images, of which 20 are for cancerous and 63 for benign cases, using a leave-one-out trial. The features selected by FOS were used in a FOS predictor and nearest-neighbour predictor and had an area under the receiver operating curve (AUC) of 0.889 and 0.791 respectively. The FOS predictor AUC is significantly improved over the signal enhancement ratio predictor with an AUC of 0.706 (p = 0.0035 for the difference in the AUCs). Moreover, using FOS-selected features in a support vector machine increased the AUC over that resulting when the features were manually selected.
PMCID: PMC3597958  PMID: 22828783
Breast cancer; Computer-aided diagnosis; Stepwise regression; Fast orthogonal search
2.  Neutropenia Prediction Based on First-Cycle Blood Counts Using a FOS-3NN Classifier 
Advances in Bioinformatics  2012;2011:172615.
Background. Delivery of full doses of adjuvant chemotherapy on schedule is key to optimal breast cancer outcomes. Neutropenia is a serious complication of chemotherapy and a common barrier to this goal, leading to dose reductions or delays in treatment. While past research has observed correlations between complete blood count data and neutropenic events, a reliable method of classifying breast cancer patients into low- and high-risk groups remains elusive. Patients and Methods. Thirty-five patients receiving adjuvant chemotherapy for early-stage breast cancer under the care of a single oncologist are examined in this study. FOS-3NN stratifies patient risk based on complete blood count data after the first cycle of treatment. All classifications are independent of breast cancer subtype and clinical markers, with risk level determined by the kinetics of patient blood count response to the first cycle of treatment. Results. In an independent test set of patients unseen by FOS-3NN, 19 out of 21 patients were correctly classified (Fisher's exact test probability P < 0.00023 [2 tailed], Matthews' correlation coefficient +0.83). Conclusions. We have developed a model that accurately predicts neutropenic events in a population treated with adjuvant chemotherapy in the first cycle of a 6-cycle treatment.
PMCID: PMC3290820  PMID: 22454638
3.  Modeling and Syndromic Surveillance for Estimating Weather-Induced Heat-Related Illness  
This paper compares syndromic surveillance and predictive weather-based models for estimating emergency department (ED) visits for Heat-Related Illness (HRI). A retrospective time-series analysis of weather station observations and ICD-coded HRI ED visits to ten hospitals in south eastern Ontario, Canada, was performed from April 2003 to December 2008 using hospital data from the National Ambulatory Care Reporting System (NACRS) database, ED patient chief complaint data collected by a syndromic surveillance system, and weather data from Environment Canada. Poisson regression and Fast Orthogonal Search (FOS), a nonlinear time series modeling technique, were used to construct models for the expected number of HRI ED visits using weather predictor variables (temperature, humidity, and wind speed). Estimates of HRI visits from regression models using both weather variables and visit counts captured by syndromic surveillance as predictors were slightly more highly correlated with NACRS HRI ED visits than either regression models using only weather predictors or syndromic surveillance counts.
PMCID: PMC3103938  PMID: 21647355
4.  PCI-SS: MISO dynamic nonlinear protein secondary structure prediction 
BMC Bioinformatics  2009;10:222.
Since the function of a protein is largely dictated by its three dimensional configuration, determining a protein's structure is of fundamental importance to biology. Here we report on a novel approach to determining the one dimensional secondary structure of proteins (distinguishing α-helices, β-strands, and non-regular structures) from primary sequence data which makes use of Parallel Cascade Identification (PCI), a powerful technique from the field of nonlinear system identification.
Using PSI-BLAST divergent evolutionary profiles as input data, dynamic nonlinear systems are built through a black-box approach to model the process of protein folding. Genetic algorithms (GAs) are applied in order to optimize the architectural parameters of the PCI models. The three-state prediction problem is broken down into a combination of three binary sub-problems and protein structure classifiers are built using 2 layers of PCI classifiers. Careful construction of the optimization, training, and test datasets ensures that no homology exists between any training and testing data. A detailed comparison between PCI and 9 contemporary methods is provided over a set of 125 new protein chains guaranteed to be dissimilar to all training data. Unlike other secondary structure prediction methods, here a web service is developed to provide both human- and machine-readable interfaces to PCI-based protein secondary structure prediction. This server, called PCI-SS, is available at . In addition to a dynamic PHP-generated web interface for humans, a Simple Object Access Protocol (SOAP) interface is added to permit invocation of the PCI-SS service remotely. This machine-readable interface facilitates incorporation of PCI-SS into multi-faceted systems biology analysis pipelines requiring protein secondary structure information, and greatly simplifies high-throughput analyses. XML is used to represent the input protein sequence data and also to encode the resulting structure prediction in a machine-readable format. To our knowledge, this represents the only publicly available SOAP-interface for a protein secondary structure prediction service with published WSDL interface definition.
Relative to the 9 contemporary methods included in the comparison cascaded PCI classifiers perform well, however PCI finds greatest application as a consensus classifier. When PCI is used to combine a sequence-to-structure PCI-based classifier with the current leading ANN-based method, PSIPRED, the overall error rate (Q3) is maintained while the rate of occurrence of a particularly detrimental error is reduced by up to 25%. This improvement in BAD score, combined with the machine-readable SOAP web service interface makes PCI-SS particularly useful for inclusion in a tertiary structure prediction pipeline.
PMCID: PMC2720391  PMID: 19615046

Results 1-4 (4)