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Motif-based protein sequence classification using neural networks.

We present a system for multi-class protein classification based on neural networks. The basic issue concerning the construction of neural network systems for protein classification is the sequence encoding scheme that must be used in order to feed the neural network. To deal with this problem we propose a method that maps a protein sequence into a numerical feature space using the matching scores of the sequence to groups of conserved patterns (called motifs) into protein families. We consider two alternative ways for identifying the motifs to be used for feature generation and provide a comparative evaluation of the two schemes. We also evaluate the impact of the incorporation of background features (2-grams) on the performance of the neural system. Experimental results on real datasets indicate that the proposed method is highly efficient and is superior to other well-known methods for protein classification.

Algorithms↗

Machine learning of functional class from phenotype data.

MOTIVATION: Mutant phenotype growth experiments are an important novel source of functional genomics data which have received little attention in bioinformatics. We applied supervised machine learning to the problem of using phenotype data to predict the functional class of Open Reading Frames (ORFs) in Saccaromyces cerevisiae. Three sources of data were used: TRansposon-Insertion Phenotypes, Localization and Expression in Saccharomyces (TRIPLES), European Functional Analysis Network (EUROFAN) and Munich Information Center for Protein Sequences (MIPS). The analysis of the data presented a number of challenges to machine learning: multi-class labels, a large number of sparsely populated classes, the need to learn a set of accurate rules (not a complete classification), and a very large amount of missing values. We modified the algorithm C4.5 to deal with these problems. RESULTS: Rules were learnt which are accurate and biologically meaningful. The rules predict function of 83 ORFs of unknown function at an estimated accuracy of > or = 80%.

Artificial Intelligence↗

Differential gene expression detection and sample classification using penalized linear regression models.

Differential gene expression detection and sample classification using microarray data have received much research interest recently. Owing to the large number of genes p and small number of samples n (p >> n), microarray data analysis poses big challenges for statistical analysis. An obvious problem owing to the 'large p small n' is over-fitting. Just by chance, we are likely to find some non-differentially expressed genes that can classify the samples very well. The idea of shrinkage is to regularize the model parameters to reduce the effects of noise and produce reliable inferences. Shrinkage has been successfully applied in the microarray data analysis. The SAM statistics proposed by Tusher et al. and the 'nearest shrunken centroid' proposed by Tibshirani et al. are ad hoc shrinkage methods. Both methods are simple, intuitive and prove to be useful in empirical studies. Recently Wu proposed the penalized t/F-statistics with shrinkage by formally using the (1) penalized linear regression models for two-class microarray data, showing good performance. In this paper we systematically discussed the use of penalized regression models for analyzing microarray data. We generalize the two-class penalized t/F-statistics proposed by Wu to multi-class microarray data. We formally derive the ad hoc shrunken centroid used by Tibshirani et al. using the (1) penalized regression models. And we show that the penalized linear regression models provide a rigorous and unified statistical framework for sample classification and differential gene expression detection.

Algorithms↗

Substring selection for biomedical document classification.

MOTIVATION: Attribute selection is a critical step in development of document classification systems. As a standard practice, words are stemmed and the most informative ones are used as attributes in classification. Owing to high complexity of biomedical terminology, general-purpose stemming algorithms are often conservative and could also remove informative stems. This can lead to accuracy reduction, especially when the number of labeled documents is small. To address this issue, we propose an algorithm that omits stemming and, instead, uses the most discriminative substrings as attributes. RESULTS: The approach was tested on five annotated sets of abstracts from iProLINK that report on the experimental evidence about five types of protein post-translational modifications. The experiments showed that Naive Bayes and support vector machine classifiers perform consistently better [with area under the ROC curve (AUC) accuracy in range 0.92-0.97] when using the proposed attribute selection than when using attributes obtained by the Porter stemmer algorithm (AUC in 0.86-0.93 range). The proposed approach is particularly useful when labeled datasets are small.

Abstracting and Indexing↗

Study design, methodology and statistical analyses in the clinical development of sparfloxacin.

Many publications in the past 10 years have emphasised the difficulties of evaluating anti-infective drugs and the need for well-designed clinical trials in this therapeutic field. The clinical development of sparfloxacin in Europe, involving more than 4000 patients in ten countries, provided the opportunity to implement a methodology for evaluation and statistical analyses which would take into account actual requirements and past insufficiencies. This methodology focused on a rigorous and accurate patient classification for evaluability, subgroups of particular interest, efficacy assessment based on automation (algorithm) and individual case review by expert panel committees. In addition, the statistical analyses did not use significance testing but rather confidence intervals to determine whether sparfloxacin was therapeutically equivalent to the reference comparator antibacterial agents.

Anti-Infective Agents↗

Comparison of computer-assigned Minnesota Codes with the visual standard method for new coronary heart disease events.

The Minnesota Code is the most widely used electrocardiogram (ECG) classification system for epidemiologic studies and has been incorporated into several Computer algorithms. The authors compared the Modular ECG Analysis System (MC-MEANS) and NOVACODE computer ECG findings with the Visual coding standard for agreement and prognostic associations with coronary heart disease (CHD) events occurring during follow-up from 1987 to 1995 in 2,116 individuals participating in the Atherosclerosis Risk in Communities (ARIC) Study. The exact agreement between Visual and computer findings was greater than 90% for all Minnesota Code categories except Q-code, which was 77% for MC-MEANS and 81% for NOVACODE. Approximately 60% of all Q-codes were assigned by computer methods only. Among the 2,116 participants, there were 246 (11.6%) new coronary events. Unadjusted relative risks for codes assigned by the three methods were similar. When computer methods disagreed on code severity, the CHD occurrence rates for MC-MEANS-detected severer code versus NOVACODE-detected severer code were 21% and 7%, respectively. This study provides clear evidence that computers assign more and severer Minnesota Codes with similar prognostic importance as does the Visual method; it also alerts researchers to potential problems in pooling Minnesota Code data read by different methods.

Algorithms↗

Is the use of psychotropic drugs associated with increased risk of ischemic heart disease?

Earlier reports of associations between panic disorder, depression, and ischemic heart disease have not evaluated the role of the drugs used to treat these conditions. As part of a larger study on reducing cardiovascular disease in an entire community, we estimated the association between psychotropic drugs and ischemic heart disease in a large community-based population using a cohort study design. We defined exposure as current use of psychotropic medications at the time of the health interview. We determined ischemic heart disease by International Classification of Diseases, 9th revision, Clinical Modification, codes and by an epidemiologic algorithm using clinical diagnostic criteria. An elevated risk for clinically significant ischemic cardiac events was moderately associated with benzodiazepine use [relative risk (RR) = 2.0; 90% confidence interval (CI) = 1.1-3.9] and strongly associated with antidepressant use (RR = 5.7; 90% CI = 2.6-12.8), although the latter estimate was based on only six antidepressant users who had an ischemic event.

Adult↗

A granular description of ECG signals.

In this paper, we develop a general framework of a granular representation of ECG signals. The crux of the approach lies in the development and ongoing processing realized in the setting of information granules-fuzzy sets. They serve as basic conceptual and semantically meaningful entities using which we describe signals and build their models (such as various predictive schemes or classifiers). A comprehensive two-phase scheme of the design of the information granules is proposed and described. At the first phase, we discuss the temporal granulation through a series of temporal windows (granular windows) and an aggregation of the values of signal by means of fuzzy sets. To address this issue, offered is a detailed method of building a fuzzy set based on numeric data and a certain optimization criterion that strikes a balance between the highest experimental relevance of the fuzzy set supported by numeric data and its substantial specificity. At the next phase of the granular design, a collection of information granules is further summarized with the use of fuzzy clustering (Fuzzy C-Means). The resulting prototypes (centroids) formed by this grouping process serve as elements of the granular vocabulary. We discuss ways of using these vocabularies in the knowledge-based representation, modeling, and classification of ECG beats.

Algorithms↗

A patient-adapting heartbeat classifier using ECG morphology and heartbeat interval features.

An adaptive system for the automatic processing of the electrocardiogram (ECG) for the classification of heartbeats into one of the five beat classes recommended by ANSI/AAMI EC57:1998 standard is presented. The heartbeat classification system processes an incoming recording with a global-classifier to produce the first set of beat annotations. An expert then validates and if necessary corrects a fraction of the beats of the recording. The system then adapts by first training a local-classifier using the newly annotated beats and combines this with the global-classifier to produce an adapted classification system. The adapted system is then used to update beat annotations. The results of this study show that the performance of a patient adaptable classifier increases with the amount of training of the system on the local record. Crucially, the performance of the system can be significantly boosted with a small amount of adaptation even when all beats used for adaptation are from a single class. This study illustrates the ability to provide highly beneficial automatic arrhythmia monitoring and is an improvement on previously reported results for automated heartbeat classification systems.

Algorithms↗

Kernel pooled local subspaces for classification.

We investigate the use of subspace analysis methods for learning low-dimensional representations for classification. We propose a kernel-pooled local discriminant subspace method and compare it against competing techniques: kernel principal component analysis (KPCA) and generalized discriminant analysis (GDA) in classification problems. We evaluate the classification performance of the nearest-neighbor rule with each subspace representation. The experimental results using several data sets demonstrate the effectiveness and performance superiority of the kernel-pooled subspace method over competing methods such as KPCA and GDA in some classification problems.

Algorithms↗

Reclassification as supervised clustering.

In some branches of science, such as molecular biology, classes may be defined but not completely trusted. Sometimes posterior analysis proves them to be partially incorrect. Despite its relevance, this phenomenon has not received much attention within the neural computation community. We define reclassification as the task of redefining some given classes by maximum likelihood learning in a model that contains both supervised and unsupervised information. This approach leads to supervised clustering with an additional complexity penalizing term on the number of new classes. As a proof of concept, a simple reclassification algorithm is designed and applied to a data set of gene sequences. To test the performance of the algorithm, two of the original classes are merged. The algorithm is capable of unraveling the original three-class hidden structure, in contrast to the unsupervised version (K-means); moreover, it predicts the subdivision of one of the original classes into two different ones.

Algorithms↗

Computational identification of strain-, species- and genus-specific proteins.

BACKGROUND: The identification of unique proteins at different taxonomic levels has both scientific and practical value. Strain-, species- and genus-specific proteins can provide insight into the criteria that define an organism and its relationship with close relatives. Such proteins can also serve as taxon-specific diagnostic targets. DESCRIPTION: A pipeline using a combination of computational and manual analyses of BLAST results was developed to identify strain-, species-, and genus-specific proteins and to catalog the closest sequenced relative for each protein in a proteome. Proteins encoded by a given strain are preliminarily considered to be unique if BLAST, using a comprehensive protein database, fails to retrieve (with an e-value better than 0.001) any protein not encoded by the query strain, species or genus (for strain-, species- and genus-specific proteins respectively), or if BLAST, using the best hit as the query (reverse BLAST), does not retrieve the initial query protein. Results are manually inspected for homology if the initial query is retrieved in the reverse BLAST but is not the best hit. Sequences unlikely to retrieve homologs using the default BLOSUM62 matrix (usually short sequences) are re-tested using the PAM30 matrix, thereby increasing the number of retrieved homologs and increasing the stringency of the search for unique proteins. The above protocol was used to examine several food- and water-borne pathogens. We find that the reverse BLAST step filters out about 22% of proteins with homologs that would otherwise be considered unique at the genus and species levels. Analysis of the annotations of unique proteins reveals that many are remnants of prophage proteins, or may be involved in virulence. The data generated from this study can be accessed and further evaluated from the CUPID (Core and Unique Protein Identification) system web site (updated semi-annually) at http://pir.georgetown.edu/cupid. CONCLUSION: CUPID provides a set of proteins specific to a genus, species or a strain, and identifies the most closely related organism.

Algorithms↗

ICD-10 coding algorithms for defining comorbidities of acute myocardial infarction.

BACKGROUND: With the introduction of ICD-10 throughout Canada, it is important to ensure that Acute Myocardial Infarction (AMI) comorbidities employed in risk adjustment methods remain valid and robust. Therefore, we developed ICD-10 coding algorithms for nine AMI comorbidities, examined the validity of the ICD-10 and ICD-9 coding algorithms in detection of these comorbidities, and assessed their performance in predicting mortality. The nine comorbidities that we examined were shock, diabetes with complications, congestive heart failure, cancer, cerebrovascular disease, pulmonary edema, acute renal failure, chronic renal failure, and cardiac dysrhythmias. METHODS: Coders generated a comprehensive list of ICD-10 codes corresponding to each AMI comorbidity. Physicians independently reviewed and determined the clinical relevance of each item on the list. To ensure that the newly developed ICD-10 coding algorithms were valid in recording comorbidities, medical charts were reviewed. After assessing ICD-10 algorithms' validity, both ICD-10 and ICD-9 algorithms were applied to a Canadian provincial hospital discharge database to predict in-hospital, 30-day, and 1-year mortality. RESULTS: Compared to chart review data as a 'criterion standard', ICD-9 and ICD-10 data had similar sensitivities (ranging from 7.1-100%), and specificities (above 93.6%) for each of the nine AMI comorbidities studied. The frequencies for the comorbidities were similar between ICD-9 and ICD-10 coding algorithms for 49,861 AMI patients in a Canadian province during 1994-2004. The C-statistics for predicting 30-day and 1 year mortality were the same for ICD-9 (0.82) and for ICD-10 data (0.81). CONCLUSION: The ICD-10 coding algorithms developed in this study to define AMI comorbidities performed similarly as past ICD-9 coding algorithms in detecting conditions and risk-adjustment in our sample. However, the ICD-10 coding algorithms should be further validated in external databases.

Adult↗

EEG classification by learning vector quantization.

EEG classification using Learning Vector Quantization (LVQ) is introduced on the basis of a Brain-Computer Interface (BCI) built in Graz, where a subject controlled a cursor in one dimension on a monitor using potentials recorded from the intact scalp. The method of classification with LVQ is described in detail along with first results on a subject who participated in four on-line cursor control sessions. Using this data, extensive off-line experiments were performed to show the influence of the various parameters of the classifier and the extracted features of the EEG on the classification results.

Algorithms↗

Surgical alternatives for treatment of articular cartilage lesions.

Articular cartilage injuries in the knee are common; fortunately, full-thickness articular cartilage defects constitute only a small portion of this group. These lesions may be incidentally encountered during ligament or meniscal surgery, having been silent or asymptomatic for an unknown period of time. However, when they are large and symptomatic, the surgeon may choose from a wide array of techniques available for treatment. The relatively small number of natural history studies regarding full-thickness articular surface lesions complicates the decision-making process. Accurate evaluation and classification of the anatomic defect aids in the development of a clinical algorithm for treatment. Surgical techniques are either reparative or restorative in nature. Reparative techniques fall short of complete reestablishment of the articular cartilage; however, the resultant repairs may remain quite functional for varying periods of time. Restorative techniques attempt to reestablish the native articular surface. To date, no peer-reviewed, prospective, randomized, controlled studies of operative versus nonoperative treatment for full-thickness articular cartilage lesions have been published. Even though the long-term results of surgical treatment for full-thickness articular surface lesions remain unknown, the early results are encouraging.

Adult↗

Statistical methods for microarray assays.

The paper shortly reviews statistical methods used in the area of DNA microarray studies. All stages of the experiment are taken into account: planning, data collection, data preprocessing, analysis and validation. Among the methods of data analysis, the algorithms for estimating differential expression, multivariate approaches, clustering methods, as well as classification and discrimination are reviewed. The need is stressed for routine statistical data processing protocols and for the search of links of microarray data analysis with quantitative genetic models.

Computational Biology↗

A comparison of the Charlson comorbidities derived from medical language processing and administrative data.

The objective of this study was to develop a medical language processing (MLP) system, which consisted of MedLEE and a set of inference rules, to identify 19 Charlson comorbidities from discharge summaries and chest x-ray reports. We used 233 cases to learn the patterns that were indicative of comorbidities for developing the inference rules. We then used an independent data set of 3,662 pneumonia patients to identify comorbidities by MLP compared with administrative data (ICD-9 codes). A stratified random sample of 190 records from disagreement cases was manually reviewed. The sensitivity, specificity, and accuracy for the MLP system/ICD-9 codes in this testing set were 0.84/0.16, 0.70/0.30, and 0.77/0.23 respectively. Thirteen of the 19 comorbidities studied were underreported in the administrative data. The kappa values ranged from 0.19 for peptic ulcer to 0.70 for lymphoma. We conclude that comorbidities derived from natural language processing of medical records can improve ICD-9-based approaches.

Adult↗