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The nearest subclass classifier: a compromise between the nearest mean and nearest neighbor classifier.

We present the Nearest Subclass Classifier (NSC), which is a classification algorithm that unifies the flexibility of the nearest neighbor classifier with the robustness of the nearest mean classifier. The algorithm is based on the Maximum Variance Cluster algorithm and, as such, it belongs to the class of prototype-based classifiers. The variance constraint parameter of the cluster algorithm serves to regularize the classifier, that is, to prevent overfitting. With a low variance constraint value, the classifier turns into the nearest neighbor classifier and, with a high variance parameter, it becomes the nearest mean classifier with the respective properties. In other words, the number of prototypes ranges from the whole training set to only one per class. In the experiments, we compared the NSC with regard to its performance and data set compression ratio to several other prototype-based methods. On several data sets, the NSC performed similarly to the k-nearest neighbor classifier, which is a well-established classifier in many domains. Also concerning storage requirements and classification speed, the NSC has favorable properties, so it gives a good compromise between classification performance and efficiency.

Algorithms↗

Overview of commonly used bioinformatics methods and their applications.

Bioinformatics, in its broad sense, involves application of computer processes to solve biological problems. A wide range of computational tools are needed to effectively and efficiently process large amounts of data being generated as a result of recent technological innovations in biology and medicine. A number of computational tools have been developed or adapted to deal with the experimental riches of complex and multivariate data and transition from data collection to information or knowledge. These include a wide variety of clustering and classification algorithms, including self-organized maps (SOM), artificial neural networks (ANN), support vector machines (SVM), fuzzy logic, and even hyphenated techniques as neuro-fuzzy networks. These bioinformatics tools are being evaluated and applied in various medical areas including early detection, risk assessment, classification, and prognosis of cancer. The goal of these efforts is to develop and identify bioinformatics methods with optimal sensitivity, specificity, and predictive capabilities.

Computational Biology↗

Predicting chemically induced duodenal ulcer and adrenal necrosis with classification trees.

Binary tree-structured statistical classification algorithms and properties of 56 model alkyl nucleophiles were brought to bear on two problems of experimental pharmacology and toxicology. Each rat of a learning sample of 745 was administered one compound and autopsied to determine the presence of duodenal ulcer or adrenal hemorrhagic necrosis. The cited statistical classification schemes were then applied to these outcomes and 67 features of the compounds to ascertain those characteristics that are associated with biologic activity. For predicting duodenal ulceration, dipole moment, melting point, and solubility in octanol are particularly important, while for predicting adrenal necrosis, important features include the number of sulfhydryl groups and double bonds. These methods may constitute inexpensive but powerful ways to screen untested compounds for possible organ-specific toxicity. Mechanisms for the etiology and pathogenesis of the duodenal and adrenal lesions are suggested, as are additional avenues for drug design.

Adrenal Gland Diseases↗

Prediction of clinical drug efficacy by classification of drug-induced genomic expression profiles in vitro.

Assays of drug action typically evaluate biochemical activity. However, accurately matching therapeutic efficacy with biochemical activity is a challenge. High-content cellular assays seek to bridge this gap by capturing broad information about the cellular physiology of drug action. Here, we present a method of predicting the general therapeutic classes into which various psychoactive drugs fall, based on high-content statistical categorization of gene expression profiles induced by these drugs. When we used the classification tree and random forest supervised classification algorithms to analyze microarray data, we derived general "efficacy profiles" of biomarker gene expression that correlate with anti-depressant, antipsychotic and opioid drug action on primary human neurons in vitro. These profiles were used as predictive models to classify naïve in vitro drug treatments with 83.3% (random forest) and 88.9% (classification tree) accuracy. Thus, the detailed information contained in genomic expression data is sufficient to match the physiological effect of a novel drug at the cellular level with its clinical relevance. This capacity to identify therapeutic efficacy on the basis of gene expression signatures in vitro has potential utility in drug discovery and drug target validation.

Algorithms↗

Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence.

The observation that laser-induced fluorescence (LIF) spectra of atherosclerotic and normal artery are different has been proposed as the basis for guiding a "smart" laser angioplasty system. The purpose of this study was to investigate the causes of this difference in LIF. Helium-cadmium laser-induced (325 nm) fluorescence was recorded from pure samples of known constituents of normal and atherosclerotic artery including collagen, elastin, calcium, cholesterol, and glycosaminoglycans. Similarities between the LIF spectra of atherosclerotic plaque and collagen and normal aorta and elastin were noted. LIF spectroscopy was then performed on specimens of atherosclerotic aortic plaque (n = 9) and normal aorta (n = 13) and on their extracted lipid, collagen, and elastin. Lipid extraction did not significantly alter atherosclerotic plaque or normal aortic LIF, suggesting a minor contribution of lipid to arterial LIF. The LIF spectra of normal aorta wall was similar to the spectra of the extracted elastin, whereas the LIF spectra of atherosclerotic aortic plaque was similar to the spectra of the extracted collagen. These observations are consistent with the reported relative collagen-to-elastin content ratio of 0.5 for normal arterial wall and 7.3 for atherosclerotic plaque. A classification algorithm was developed to discriminate normal and atherosclerotic aortic spectra based on an elastin and collagen spectral decomposition. A discriminant score was formed by the difference of elastin and collagen (E-C) coefficients and used to classify 182 aortic fluorescence spectra. The mean E-C value was +0.83 +/- 0.04 for normal and -0.48 +/- 0.07 for atherosclerotic aorta (p less than 0.001). Classification accuracy was 92%.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

ECG characterization of paroxysmal atrial fibrillation: parameter extraction and automatic diagnosis algorithm.

Paroxysmal atrial fibrillation (PAF) is one of the most common heart arrhythmias. It is very difficult to detect unless an explicit Atrial Fibrillation episode occurs during the exploration. The present paper describes a number of low level parameters extracted from ECG traces where no Atrial Fibrillation process is present. The ability of this parameter set to characterize PAF patients is studied and discussed. Based on these parameters a modular automatic classification algorithm for PAF diagnosis is developed and evaluated.

Algorithms↗

Correlation-based pattern recognition for implantable defibrillators.

An estimated 300,000 Americans die each year from cardiac arrhythmias. Historically, drug therapy or surgery were the only treatment options available for patients suffering from arrhythmias. Recently, implantable arrhythmia management devices have been developed. These devices allow abnormal cardiac rhythms to be sensed and corrected in vivo. Proper arrhythmia classification is critical to selecting the appropriate therapeutic intervention. The classification problem is made more challenging by the power/computation constraints imposed by the short battery life of implantable devices. Current devices utilize heart rate-based classification algorithms. Although easy to implement, rate-based approaches have unacceptably high error rates in distinguishing supraventricular tachycardia (SVT) from ventricular tachycardia (VT). Conventional morphology assessment techniques used in ECG analysis often require too much computation to be practical for implantable devices. In this paper, a computationally-efficient, arrhythmia classification architecture using correlation-based morphology assessment is presented. The architecture classifies individuals heart beats by assessing similarity between an incoming cardiac signal vector and a series of prestored class templates. A series of these beat classifications are used to make an overall rhythm assessment. The system makes use of several new results in the field of pattern recognition. The resulting system achieved excellent accuracy in discriminating SVT and VT.

Arrhythmias, Cardiac↗

Microscopic image analysis for quantitative measurement and feature identification of normal and cancerous colonic mucosa.

The development of an automated algorithm for the categorization of normal and cancerous colon mucosa is reported. Six features based on texture analysis were studied. They were derived using the co-occurrence matrix and were angular second moment, entropy, contrast, inverse difference moment, dissimilarity, and correlation. Optical density was also studied. Forty-four normal images and 58 cancerous images from sections of the colon were analyzed. These two groups were split equally into two subgroups: one set was used for supervised training and the other to test the classification algorithm. A stepwise selection procedure showed that correlation and entropy were the features that discriminated most strongly between normal and cancerous tissue (P < 0.0001). A parametric linear-discriminate function was used to determine the classification rule. For the training set, a sensitivity and specificity of 93.1% and 81.8%, respectively, were achieved, with an overall accuracy of 88.2%. These results were confirmed with the test set, with a sensitivity and specificity of 93.1% and 86.4%, respectively, and an overall accuracy of 90.2%.

Colon↗

Molecular staging of lymph nodes from patients with esophageal adenocarcinoma.

PURPOSE: This study was designed to evaluate molecular markers for the detection of micrometastasis in esophageal adenocarcinoma, define algorithms to distinguish positive from benign lymph nodes and to validate these findings in an independent tissue set and in patients with p(N0) esophageal adenocarcinoma. EXPERIMENTAL DESIGN: Potential markers were identified through literature and database searches. All markers were analyzed by quantitative reverse transcription (QRT)-PCR on a limited set of primary tumors and benign lymph nodes. Selected markers were further evaluated on a larger tissue set and classification algorithms were generated for individual markers and combinations. Algorithms were statistically validated internally as well as externally on an independent set of lymph nodes. Selected markers were then used to identify occult disease in lymph nodes from 34 patients with p(N0) esophageal adenocarcinoma. RESULTS: Thirty-nine markers were evaluated, six underwent further analysis and five were analyzed in the external validation study. Two markers provided perfect classification in both the screening and validation sets, although parametric bootstrap analysis estimated 2% to 3% optimism in the observed classification accuracy. Several marker combinations also gave perfect classification in the observed data sets, and estimates of optimism were lower, implying more robust classification than with individual markers alone. Five of thirty-four patients with esophageal adenocarcinoma had positive nodes by multimarker QRT-PCR analysis and disease-free survival was significantly worse in these patients (P = 0.0023). CONCLUSIONS: We have identified novel QRT-PCR markers for the detection of occult lymph node disease in patients with esophageal adenocarcinoma. The objective nature of QRT-PCR results, and the ability to detect occult metastases, make this an attractive alternative to routine pathology.

Adenocarcinoma↗

Using wavelet transform and fuzzy neural network for VPC detection from the Holter ECG.

A novel method for detecting ventricular premature contraction (VPC) from the Holter system is proposed using wavelet transform (WT) and fuzzy neural network (FNN). The basic ideal and major advantage of this method is to reuse information that is used during QRS detection, a necessary step for most ECG classification algorithm, for VPC detection. To reduce the influence of different artifacts, the filter bank property of quadratic spline WT is explored. The QRS duration in scale three and the area under the QRS complex in scale four are selected as the characteristic features. It is found that the R wave amplitude has a marked influence on the computation of proposed characteristic features. Thus, it is necessary to normalize these features. This normalization process can reduce the effect of alternating R wave amplitude and achieve reliable VPC detection. After normalization and excluding the left bundle branch block beats, the accuracies for VPC classification using FNN is 99.79%. Features that are extracted using quadratic spline wavelet were used successfully by previous investigators for QRS detection. In this study, using the same wavelet, it is demonstrated that the proposed feature extraction method from different WT scales can effectively eliminate the influence of high and low-frequency noise and achieve reliable VPC classification. The two primary advantages of using same wavelet for QRS detection and VPC classification are less computation and less complexity during actual implementation.

Algorithms↗

Diagnostic value of the RR-variability indicators for mild hypertension.

Experimental and clinical studies have shown that an imbalance of the cardiovascular system autonomous regulation can lead to complications. In this study we have aimed to investigate whether the vegetative control of patients with mild hypertension is disturbed and to evaluate the power of the RR-variability indicators to detect the disturbances. RR variability has been studied in two groups of individuals: normotensive and mildly hypertensive. The indicators of the heart rate variability (HRV) from the 'Cardiovit CS-100 ECG Module' electrocardiograph have been used. The HRV is known to exhibit circadian variations, therefore RR intervals were recorded in two separate sessions: morning (8-9 am) and afternoon (2-3 pm). Each session included three tests: in a resting state, with a handgrip test and with the Valsalva manoeuvre. The multivariate statistical method was applied separately to the morning and afternoon data. A number of classification algorithms were synthesized, yielding correct recognition of normotensive and mildly hypertensive subjects of 91.9% and 94.2% for the morning and afternoon sessions, respectively. We have thoroughly discussed the substantiating reasons for the high statistical significance and reliability of the discrimination obtained. The high sensitivity and specificity of the RR-variability indicators included in the classification models suggest correlative changes of the nervous system vegetative balance in mildly hypertensive patients. The results of the study show the possibility for statistically significant diagnosis of mild hypertension, for prediction of ventricular arrhythmia, left ventricular hypertrophy and ischaemic heart disease.

Adult↗

Autofluorescence characteristics of healthy oral mucosa at different anatomical sites.

BACKGROUND AND OBJECTIVES: Autofluorescence spectroscopy is a promising tool for oral cancer detection. Its reliability might be improved by using a reference database of spectra from healthy mucosa. We investigated the influence of anatomical location on healthy mucosa autofluorescence. STUDY DESIGN/MATERIALS AND METHODS: Spectra were recorded from 97 volunteers using seven excitation wavelengths (350-450 nm), 455-867 nm emission. We studied intensity and applied principal component analysis (PCA) with classification algorithms. Class overlap estimates were calculated. RESULTS: We observed differences in fluorescence intensity between locations. These were significant but small compared to standard deviations (SD). Normalized spectra looked similar for locations, except for the dorsal side of the tongue (DST) and the vermilion border (VB). Porphyrin-like fluorescence was observed frequently, especially at DST. PCA and classification confirmed VB and DST to be spectrally distinct. The remaining locations showed large class overlaps. CONCLUSIONS: No relevant systematic spectral differences have been observed between most locations, allowing the use of one large reference database. For DST and VB separate databases are required.

Adolescent↗

Nonspecific and attenuated negative symptoms in patients at clinical high-risk for schizophrenia.

BACKGROUND: Retrospective studies have shown that nonspecific psychopathology and negative symptoms, including social isolation and academic dysfunction, tend to precede onset of psychosis. The present report describes the baseline psychopathology of subjects in the Hillside Recognition and Prevention (RAP) Program, and presents an operationalized classification algorithm for the prospective study of both positive and negative symptoms of clinical high-risk (CHR) for schizophrenia. METHODS: Eighty-two adolescent and young adult patients were characterized using semi-structured interviews of both a parent informant and the patient. The Scale of Prodromal Symptoms (SOPS) was utilized to derive a three-part classification scheme: CHR- subjects (n=20) were defined as having at least one attenuated negative symptom with no positive symptoms; CHR+ subjects (n=42) were defined as having one or more attenuated positive symptoms without psychosis; schizophrenia-like psychosis (SLP) subjects (n=20) were defined as having a psychotic symptom, but without meeting criterion A, B, or C of DSM-IV schizophrenia. RESULTS: Social isolation was the most common presenting symptom. The three RAP subgroups did not significantly differ in levels of attenuated negative and disorganized symptoms, despite the fact that these were not required for inclusion in the CHR+ and SLP groups. Common co-morbid diagnoses included major depression, attention deficit hyperactivity disorder, avoidant personality disorder, and Cluster A personality disorders. CONCLUSIONS: Negative symptoms and other nonspecific behavioral abnormalities represent clinically important phenomena in prodromal patients, and may provide insight into pathophysiologic mechanisms in schizophrenia and possible preventive interventions.

Adolescent↗

Classification of communication signals of the little brown bat.

Little brown bats, Myotis lucifugus, are known for their ability to echolocate and utilize their echolocation system to navigate, and locate and identify prey. Their echolocation signals have been characterized in detail but their communication signals are less well understood despite their widespread use during social interactions. The goal of this study was to develop an automatic classification algorithm for characterizing the communication signals of little brown bats. Sound recordings were made overnight on five individual male bats (housed separately from a large group of captive bats) for 7 nights, using a bat detector and a digital recorder. The spectral and temporal characteristics of recorded sounds were first analyzed and classified by visual observation of a call's temporal pattern and spectral composition. Sounds were later classified using an automatic classification scheme based on multivariate statistical parameters in MATLAB. Human- and machine-based analysis revealed five discrete classes of bat's communication signals: downward frequency-modulated calls, steep frequency-modulated calls, constant frequency calls, broadband noise bursts, and broadband click trains.

Algorithms↗

Clinical applicability of transient evoked otoacoustic emissions: identification and classification of hearing loss.

The study aimed at the development of a clinically applicable methodology that could: (1) discriminate transient evoked otoacoustic emission (TEOAE) recordings from normal hearing or hearing impaired individuals; (2) classify the nature of the hearing loss as conductive or as cochlear, and (3) define clear-cut TEOAE clinical criteria. A classification algorithm based on a multivariate discriminant analysis of fast Fourier transform data from recordings evoked by click stimuli of 50 +/- 2, 62 +/- 2, 68 +/- 2 and 80 +/- 2 dB SPL was used to discriminate 302 normal subjects from 383 subjects suffering from mild to moderate hearing losses. The best discriminant model (QDF80) produced a sensitivity of 93.8% and a specificity of 79.4%. When extra correlation criteria were serially applied to the classification outcome, the specificity was increased to 85.3%, but the sensitivity was marginally decreased to 91.7%. The classification of the correctly identified hearing-impaired cases yielded 93.8% identification of conductive and 75.1% identification of cochlear cases. A sensitivity analysis of the misclassified hearing-impaired cases suggested that the TEOAE spectra are well correlated with the 2-kHz but poorly correlated with the 4-kHz octave frequency.

Acoustic Stimulation↗

Recent advances in EEG data processing.

It is argued that the most interesting advances in EEG signal processing are with methods based on descriptive mathematical models of the process. Formulation of auto-regressive (AR) and mixed autoregressive and moving average (ARMA) models is reviewed for the scalar and the multidimensional cases and extensions to allow time-varying coefficients are pointed out. Data processing with parametric models, DPPM, involves parameter estimation and a large number of algorithms are available. Emphasis is put on those that are simple to apply and require a modest amount of computation. A recursive algorithm by Levinson, Robinson and Durbin is well suited for estimation of the coefficients in the AR model and for tests of model order. It is applicable to both the scalar and multidimensional cases. The ARMA model can be handled by approximation of an AR model or by nonlinear optimization. Recursive estimation with AR and ARMA models is reviewed and the connection with the Kalman filter pointed out. In this way processes with time-varying properties may be handled and a stationarity index is defined. The recursive algorithms can deal with AR or ARMA models in the same way. A reformulation of the algorithm to include sparsely updated parameter estimates significantly speeds up the calculations. It will allow several EEG channels to be handled simultaneously in real time on a modern minicomputer installation. DPPM has been particularly successful in the areas of spectral analysis and detection of short transients such as spikes and sharp waves. Recently some interesting attempts have been made to apply classification algorithms to estimated parameters. A brief review is made of the main results in these areas.

Electroencephalography↗

Method-based differences in the automated analysis of the three-dimensional morphology of trabecular bone.

The three-dimensional (3D) morphology of trabecular bone is frequently quantified using computer programs. However, there are no standardized implementations of morphology programs and many variations are possible. Even though programs may use the same basic method, results can be significantly different because of differences in implementation. Morphology data from different laboratories therefore may not be comparable. The method of directed secants, with parallel plate assumptions, is commonly used to quantify 3D morphology. We examined the effect of several variations in the implementation of this method on measurements of trabecular plate number (Tb.N), trabecular thickness, and trabecular spacing. Three-dimensional micromagnetic resonance images of 10 bovine trabecular bone specimens were analyzed using several variations of the directed secant method. An analysis of covariance with repeated measures suggested that variations in the algorithm used to count test line intersections, variations in the criteria used to classify a test coordinate as bone or marrow, and variations in the number of test grid rotations had significant effects on Tb.N (p < 0.0001). The largest difference in Tb.N (52%) was due to the method used to count test line intersections with the bone-marrow interface. Variations in the classification algorithm and variations in the number of test line grid rotations resulted in a 6% difference in Tb.N. The spacing of the test line grids did not affect Tb.N (p = 0.28), and all differences were independent of volume fraction (p = 0.67). These data show that there can be significant differences in trabecular bone morphology measurements due only to the method used for the measurements. To facilitate comparisons between laboratories, we have made validated computer programs to measure trabecular bone morphology available over the Internet.

Algorithms↗

Distinction of renal cell carcinomas from high-attenuation renal cysts at portal venous phase contrast-enhanced CT.

PURPOSE: To determine if renal cell carcinomas can be distinguished from high-attenuation renal cysts on portal venous phase contrast material-enhanced computed tomographic (CT) scans. MATERIALS AND METHODS: Fifty-seven renal cell carcinomas and 37 high-attenuation (>20 HU) renal cysts that were at least 1 cm in diameter were retrospectively identified in 90 patients who underwent portal venous phase contrast-enhanced CT. Two independent readers recorded the CT number and degree of internal heterogeneity (uniform or mildly, moderately, or markedly heterogeneous) of all lesions. Logistic regression analysis with adjustment for the two readers was used to examine the association between clinical and CT parameters and the final diagnosis. Stepwise logistic regression analysis was used to identify independent distinguishing variables, which were then incorporated in a classification and regression tree analysis to construct the most efficient classification algorithm. RESULTS: Renal cell carcinomas were of significantly greater size (5.10 cm vs 2.84 cm, P <.001), mean attenuation (101.2 HU vs 55.3 HU, P <.001), and internal heterogeneity (P <.001) than high-attenuation renal cysts. Stepwise logistic regression showed attenuation and internal heterogeneity were both independent variables associated with final diagnosis, but lesion size was not an independent distinguishing variable after adjustment for internal heterogeneity. Classification and regression tree analysis demonstrated that an attenuation greater than 70 HU or the presence of moderate or marked internal heterogeneity was an accurate sign of renal cell carcinoma, with a sensitivity of 91% (52 of 57) for both readers and a specificity of 92% (34 of 37) for reader 1 and 84% (31 of 37) for reader 2. CONCLUSION: On portal venous phase contrast-enhanced CT scans, attenuation greater than 70 HU or moderate or marked internal heterogeneity favor a diagnosis of renal cell carcinoma over a diagnosis of high-attenuation renal cyst.

Adult↗