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A spatio-temporal Bayesian network classifier for understanding visual field deterioration.

OBJECTIVE: Progressive loss of the field of vision is characteristic of a number of eye diseases such as glaucoma which is a leading cause of irreversible blindness in the world. Recently, there has been an explosion in the amount of data being stored on patients who suffer from visual deterioration including field test data, retinal image data and patient demographic data. However, there has been relatively little work in modelling the spatial and temporal relationships common to such data. In this paper we introduce a novel method for classifying visual field (VF) data that explicitly models these spatial and temporal relationships. METHODOLOGY: We carry out an analysis of our proposed spatio-temporal Bayesian classifier and compare it to a number of classifiers from the machine learning and statistical communities. These are all tested on two datasets of VF and clinical data. We investigate the receiver operating characteristics curves, the resulting network structures and also make use of existing anatomical knowledge of the eye in order to validate the discovered models. RESULTS: Results are very encouraging showing that our classifiers are comparable to existing statistical models whilst also facilitating the understanding of underlying spatial and temporal relationships within VF data. The results reveal the potential of using such models for knowledge discovery within ophthalmic databases, such as networks reflecting the 'nasal step', an early indicator of the onset of glaucoma. CONCLUSION: The results outlined in this paper pave the way for a substantial program of study involving many other spatial and temporal datasets, including retinal image and clinical data.

Algorithms↗

Neural network predictions of significant coronary artery stenosis in men.

OBJECTIVE: A neural network system was designed to predict whether coronary arteriography on a given patient would reveal any occurrence of significant coronary stenosis (>50%), a degree of stenosis which often leads to coronary intervention. METHODOLOGY: A dataset of 2004 records from male cardiology patients was derived from a national cardiac catheterization database. The catheterizations selected for analysis from the database were first-time and elective, and they were precipitated by chest pain. Eleven patient variables were used as inputs in an artificial neural network system. The network was trained on the earliest 902 records in the dataset. The next 902 records formed a cross-validation file, which was used to optimize the training. A third file composed of the next 100 records facilitated the choice of a cutoff number between 0 and 1. The cutoff number was applied to the last 100 records, which comprised a test file. RESULTS: When a cutoff of 0.25 was compared to the network outputs of all 100 records in the test file, 12 of 46 (specificity=26%) patients without significant stenosis had outputs 0.25 (sensitivity=100%). Therefore, the network identified a fraction of the patients in the test file who did not have significant coronary artery stenosis, while at the same time the network identified all of the patients in the test file who had significant stenosis capable of causing chest pain. CONCLUSION: Artificial neural networks may be helpful in reducing unnecessary cardiac catheterizations.

Cardiac Catheterization↗

Computational modeling of oligonucleotide positional densities for human promoter prediction.

OBJECTIVE: The gene promoter region controls transcriptional initiation of a gene, which is the most important step in gene regulation. In-silico detection of promoter region in genomic sequences has a number of applications in gene discovery and understanding gene expression regulation. However, computational prediction of eukaryotic poly-II promoters has remained a difficult task. This paper introduces a novel statistical technique for detecting promoter regions in long genomic sequences. METHOD: A number of existing techniques analyze the occurrence frequencies of oligonucleotides in promoter sequences as compared to other genomic regions. In contrast, the present work studies the positional densities of oligonucleotides in promoter sequences. The analysis does not require any non-promoter sequence dataset or any model of the background oligonucleotide content of the genome. The statistical model learnt from a dataset of promoter sequences automatically recognizes a number of transcription factor binding sites simultaneously with their occurrence positions relative to the transcription start site. Based on this model, a continuous naïve Bayes classifier is developed for the detection of human promoters and transcription start sites in genomic sequences. RESULTS: The present study extends the scope of statistical models in general promoter modeling and prediction. Promoter sequence features learnt by the model correlate well with known biological facts. Results of human transcription start site prediction compare favorably with existing 2nd generation promoter prediction tools.

Base Sequence↗

Auditory brainstem response classification: a hybrid model using time and frequency features.

OBJECTIVE: The auditory brainstem response (ABR) is an evoked response obtained from brain electrical activity when an auditory stimulus is applied to the ear. An audiologist can determine the threshold level of hearing by applying stimuli at reducing levels of intensity, and can also diagnose various otological, audiological, and neurological abnormalities by examining the morphology of the waveform and the latencies of the individual waves. This is a subjective process requiring considerable expertise. The aim of this research was to develop software classification models to assist the audiologist with an automated detection of the ABR waveform and also to provide objectivity and consistency in this detection. MATERIALS AND METHODS: The dataset used in this study consisted of 550 waveforms derived from tests using a range of stimulus levels applied to 85 subjects ranging in hearing ability. Each waveform had been classified by a human expert as 'response=Yes' or 'response=No'. Individual software classification models were generated using time, frequency and cross-correlation measures. Classification employed both artificial neural networks (NNs) and the C5.0 decision tree algorithm. Accuracies were validated using six-fold cross-validation, and by randomising training, validation and test datasets. RESULTS: The result was a two stage classification process whereby strong responses were classified to an accuracy of 95.6% in the first stage. This used a ratio of post-stimulus to pre-stimulus power in the time domain, with power measures at 200, 500 and 900Hz in the frequency domain. In the second stage, outputs from time, frequency and cross-correlation classifiers were combined using the Dempster-Shafer method to produce a hybrid model with an accuracy of 85% (126 repeat waveforms). CONCLUSION: By combining the different approaches a hybrid system has been created that emulates the approach used by an audiologist in analysing an ABR waveform. Interpretation did not rely on one particular feature but brought together power and frequency analysis as well as consistency of subaverages. This provided a system that enhanced robustness to artefacts while maintaining classification accuracy.

Acoustic Stimulation↗

Beyond predictive performance: A systematic review and critical methodological appraisal of AI/ML and conventional modelling strategies in breast, colorectal, and pancreatic Cancer.

BACKGROUND: Predictive modelling for cancer risk, treatment-related complications, and survival is central to precision oncology. Conventional logistic regression (LR) and Cox proportional hazards (CoxPH) regression remain widely used but are limited when modelling nonlinear interactions, high-dimensional imaging features, and multimodal clinical-metabolic predictors. Artificial intelligence (AI) and machine learning (ML) methods offer expanded capability through automated feature extraction, ensemble learning, and flexible survival modelling, but the evidence on when AI/ML adds value over conventional models across cancer sites and predictive tasks remains fragmented. OBJECTIVE: To systematically evaluate the methodological performance, validation strategies, and translational limitations of AI/ML models compared with conventional statistical models in published predictive-modelling studies for breast, colorectal, or pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for studies published between January 2019 and March 2025. Two reviewers independently conducted title-and-abstract screening, full-text eligibility assessment, and PROBAST risk-of-bias assessment. Sixty-five studies (n = 907,567 participants) were narratively synthesised by cancer site, predictive task, model family, comparator, validation strategy, predictor modality, and calibration or explainability reporting. RESULTS: The 65 studies comprised breast cancer (n = 35), colorectal cancer (n = 21), and pancreatic cancer (n = 9). AI/ML superiority over LR and CoxPH was task- and data-dependent. CNN- and U-Net-based models predominated in imaging and body-composition tasks, tree-based ensembles consistently outperformed LR for tabular perioperative complication prediction, and CoxPH remained competitive, and in the largest pancreatic risk study, superior to XGBoost (C-index 0.802 vs 0.723) in well-structured datasets. PROBAST analysis-domain risk was moderate in 54 of 65 studies (83%), driven by limited external validation, sparse calibration reporting (11/65), and few decision-curve analyses (7/65). CONCLUSION: AI/ML adds the most methodological value in imaging-derived feature extraction and nonlinear perioperative prediction, while conventional regression remains preferable in large, structured datasets with linear predictors. Clinical translation requires standardised body-composition definitions, external validation, calibration assessment, decision-curve analysis, and explainability, in line with TRIPOD+AI and CLAIM standards.

Humans↗

On the statistical analysis of the GS-NS0 cell proteome: imputation, clustering and variability testing.

We have undertaken two-dimensional gel electrophoresis proteomic profiling on a series of cell lines with different recombinant antibody production rates. Due to the nature of gel-based experiments not all protein spots are detected across all samples in an experiment, and hence datasets are invariably incomplete. New approaches are therefore required for the analysis of such graduated datasets. We approached this problem in two ways. Firstly, we applied a missing value imputation technique to calculate missing data points. Secondly, we combined a singular value decomposition based hierarchical clustering with the expression variability test to identify protein spots whose expression correlates with increased antibody production. The results have shown that while imputation of missing data was a useful method to improve the statistical analysis of such data sets, this was of limited use in differentiating between the samples investigated, and highlighted a small number of candidate proteins for further investigation.

Algorithms↗

A new hybrid approach to predict subcellular localization of proteins by incorporating gene ontology.

Based on the recent development in the gene ontology and functional domain databases, a new hybridization approach is developed for predicting protein subcellular location by combining the gene product, functional domain, and quasi-sequence-order effects. As a showcase, the same prokaryotic and eukaryotic datasets, which were studied by many previous investigators, are used for demonstration. The overall success rate by the jackknife test for the prokaryotic set is 94.7% and that for the eukaryotic set 92.9%. These are so far the highest success rates achieved for the two datasets by following a rigorous cross-validation test procedure, suggesting that such a hybrid approach may become a very useful high-throughput tool in the area of bioinformatics, proteomics, as well as molecular cell biology. The very high success rates also reflect the fact that the subcellular localization of a protein is closely correlated with: (1). the biological objective to which the gene or gene product contributes, (2). the biochemical activity of a gene product, and (3). the place in the cell where a gene product is active.

Algorithms↗

A comparison of siRNA efficacy predictors.

Short interfering RNA (siRNA) efficacy prediction algorithms aim to increase the probability of selecting target sites that are applicable for gene silencing by RNA interference. Many algorithms have been published recently, and they base their predictions on such different features as duplex stability, sequence characteristics, mRNA secondary structure, and target site uniqueness. We compare the performance of the algorithms on a collection of publicly available siRNAs. First, we show that our regularized genetic programming algorithm GPboost appears to have a higher and more stable performance than other algorithms on the collected datasets. Second, several algorithms gave close to random classification on unseen data, and only GPboost and three other algorithms have a reasonably high and stable performance on all parts of the dataset. Third, the results indicate that the siRNAs' sequence is sufficient input to siRNA efficacy algorithms, and that other features that have been suggested to be important may be indirectly captured by the sequence.

Algorithms↗

Correlations between genomic GC levels and optimal growth temperatures are not 'robust'.

Musto et al. [FEBS Lett. 573 (2004) 73] studied the correlations between GC levels and optimal growth temperatures in 20 prokaryotic families. They reported that positive correlations are generally observed, and many of these are significant. Here, we have shown that these correlations are not "robust," i.e., correlation coefficients and/or significance of correlations can be considerably influenced by exclusion of very few (even as small as one) species from each dataset. The sensitivity of correlations is assumed as a result of high levels of bias in the family datasets. We concluded that solely based on these data, one cannot establish that GC contents of prokaryotic genomes increase as a result of growth temperature increments.

Adaptation, Physiological↗

Using GO-PseAA predictor to predict enzyme sub-class.

Enzyme function is much less conserved than anticipated, i.e., the requirement for sequence similarity that implies similarity in enzymatic function is much higher than the requirement that implies similarity in protein structure. This is because the function of an enzyme is an extremely complicated problem that may involve very subtle structural details as well as many other physical chemistry factors. Accordingly, if simply based on the sequence similarity approach, it would hardly get a decent success rate in predicting enzyme sub-class even for a dataset consisting of samples with 50% sequence identity. To cope with such a situation, the GO-PseAA predictor was adopted to identify the sub-class for each of the six main enzyme families. It has been observed that, even for the much more stringent datasets in which none of the enzymes has 25% sequence identity to any others, the overall success rates are 73-95%, suggesting that the GO-PseAA predictor can catch the core features of the statistical samples concerned and may become a useful high throughput tool in proteomics and bioinformatics.

Algorithms↗

Using supervised fuzzy clustering to predict protein structural classes.

Prediction of protein classification is both an important and a tempting topic in protein science. This is because of not only that the knowledge thus obtained can provide useful information about the overall structure of a query protein, but also that the practice itself can technically stimulate the development of novel predictors that may be straightforwardly applied to many other relevant areas. In this paper, a novel approach, the so-called "supervised fuzzy clustering approach" is introduced that is featured by utilizing the class label information during the training process. Based on such an approach, a set of "if-then" fuzzy rules for predicting the protein structural classes are extracted from a training dataset. It has been demonstrated through two different working datasets that the overall success prediction rates obtained by the supervised fuzzy clustering approach are all higher than those by the unsupervised fuzzy c-means introduced by the previous investigators [C.T. Zhang, K.C. Chou, G.M. Maggiora. Protein Eng. (1995) 8, 425-435]. It is anticipated that the current predictor may play an important complementary role to other existing predictors in this area to further strengthen the power in predicting the structural classes of proteins and their other characteristic attributes.

Algorithms↗

Prediction of protease types in a hybridization space.

Regulating most physiological processes by controlling the activation, synthesis, and turnover of proteins, proteases play pivotal regulatory roles in conception, birth, digestion, growth, maturation, ageing, and death of all organisms. Different types of proteases have different functions and biological processes. Therefore, it is important for both basic research and drug discovery to consider the following two problems. (1) Given the sequence of a protein, can we identify whether it is a protease or non-protease? (2) If it is, what protease type does it belong to? Although the two problems can be solved by various experimental means, it is both time-consuming and costly to do so. The avalanche of protein sequences generated in the post-genetic era has challenged us to develop an automated method for making a fast and reliable identification. By hybridizing the functional domain composition and pseudo-amino acid composition, we have introduced a new method called "FunD-PseAA predictor" that is operated in a hybridization space. To avoid redundancy and bias, demonstrations were performed on a dataset where none of the proteins has >or=25% sequence identity to any other. The overall success rate thus obtained by the jackknife cross-validation test in identifying protease and non-protease was 92.95%, and that in identifying the protease type was 94.75% among the following six types: (1) aspartic, (2) cysteine, (3) glutamic, (4) metallo, (5) serine, and (6) threonine. Demonstration was also made on an independent dataset, and the corresponding overall success rates were 98.36% and 97.11%, respectively, suggesting the FunD-PseAA predictor is very powerful and may become a useful tool in bioinformatics and proteomics.

Algorithms↗

Hum-PLoc: a novel ensemble classifier for predicting human protein subcellular localization.

Predicting subcellular localization of human proteins is a challenging problem, especially when unknown query proteins do not have significant homology to proteins of known subcellular locations and when more locations need to be covered. To tackle the challenge, protein samples are expressed by hybridizing the gene ontology (GO) database and amphiphilic pseudo amino acid composition (PseAA). Based on such a representation frame, a novel ensemble classifier, called "Hum-PLoc", was developed by fusing many basic individual classifiers through a voting system. The "engine" of these basic classifiers was operated by the KNN (K-nearest neighbor) rule. As a demonstration, tests were performed with the ensemble classifier for human proteins among the following 12 locations: (1) centriole; (2) cytoplasm; (3) cytoskeleton; (4) endoplasmic reticulum; (5) extracell; (6) Golgi apparatus; (7) lysosome; (8) microsome; (9) mitochondrion; (10) nucleus; (11) peroxisome; (12) plasma membrane. To get rid of redundancy and homology bias, none of the proteins investigated here had > or = 25% sequence identity to any other in a same subcellular location. The overall success rates thus obtained via the jackknife cross-validation test and independent dataset test were 81.1% and 85.0%, respectively, which are more than 50% higher than those obtained by the other existing methods on the same stringent datasets. Furthermore, an incisive and compelling analysis was given to elucidate that the overwhelmingly high success rate obtained by the new predictor is by no means due to a trivial utilization of the GO annotations. This is because, for those proteins with "subcellular location unknown" annotation in Swiss-Prot database, most (more than 99%) of their corresponding GO numbers in GO database are also annotated with "cellular component unknown". The information and clues for predicting subcellular locations of proteins are actually buried into a series of tedious GO numbers, just like they are buried into a pile of complicated amino acid sequences although with a different manner and "depth". To dig out the knowledge about their locations, a sophisticated operation engine is needed. And the current predictor is one of these kinds, and has proved to be a very powerful one. The Hum-PLoc classifier is available as a web-server at http://202.120.37.186/bioinf/hum.

Algorithms↗

Integrating a functional proteomic approach into the target discovery process.

Functional proteomics is a promising technique for the rational identification of novel therapeutic targets by elucidation of the function of newly identified proteins in disease-relevant cellular pathways. Of the recently described high-throughput approaches for analyzing protein-protein interactions, the yeast two-hybrid (Y2H) system has turned out to be one of the most suitable for genome-wide analysis. However, this system presents a challenging technical problem: the high prevalence of false positives and false negatives in datasets due to intrinsic limitations of the technology and the use of a high-throughput, genetic assay. We discuss here the different experimental strategies applied to Y2H assays, their general limitations and advantages. We also address the issue of the contribution of protein interaction mapping to functional biology, especially when combined with complementary genomic and proteomic analyses. Finally, we illustrate how the combination of protein interaction maps with relevant functional assays can provide biological support to large-scale protein interaction datasets and contribute to the identification and validation of potential therapeutic targets.

Animals↗

The correlation grid: analysis of synchronous spiking in multi-dimensional spike train data and identification of feasible connection architectures.

This paper presents a visualization technique specifically designed to support the analysis of synchronous firings in multiple, simultaneously recorded, spike trains. This technique, called the correlation grid, enables investigators to identify groups of spike trains, where each pair of spike trains has a high probability of generating spikes approximately simultaneously or within a constant time shift. Moreover, the correlation grid was developed to help solve the following reverse problem: identification of the connection architecture between spike train generating units, which may produce a spike train dataset similar to the one under analysis. To demonstrate the efficacy of this approach, results are presented from a study of three simulated, noisy, spike train datasets. The parameters of the simulated neurons were chosen to reflect the typical characteristics of cortical pyramidal neurons. The schemes of neuronal connections were not known to the analysts. Nevertheless, the correlation grid enabled the analysts to find the correct connection architecture for each of these three data sets.

Action Potentials↗

On the use of multi-objective evolutionary algorithms for survival analysis.

This paper proposes and evaluates a multi-objective evolutionary algorithm for survival analysis. One aim of survival analysis is the extraction of models from data that approximate lifetime/failure time distributions. These models can be used to estimate the time that an event takes to happen to an object. To use of multi-objective evolutionary algorithms for survival analysis has several advantages. They can cope with feature interactions, noisy data, and are capable of optimising several objectives. This is important, as model extraction is a multi-objective problem. It has at least two objectives, which are the extraction of accurate and simple models. Accurate models are required to achieve good predictions. Simple models are important to prevent overfitting, improve the transparency of the models, and to save computational resources. Although there is a plethora of evolutionary approaches to extract models for classification and regression, the presented approach is one of the first applied to survival analysis. The approach is evaluated on several artificial datasets and one medical dataset. It is shown that the approach is capable of producing accurate models, even for problems that violate some of the assumptions made by classical approaches.

Algorithms↗

Benchmarking a memetic algorithm for ordering microarray data.

This work introduces a new algorithm for "gene ordering". Given a matrix of gene expression data values, the task is to find a permutation of the gene names list such that genes with similar expression patterns should be relatively close in the permutation. The algorithm is based on a combined approach that integrates a constructive heuristic with evolutionary and Tabu Search techniques in a single methodology. To evaluate the benefits of this method, we compared our results with the current outputs provided by several widely used algorithms in functional genomics. We also compared the results with our own hierarchical clustering method when used in isolation. We show that the use of images, corrupted with known levels of noise, helps to illustrate some aspects of the performance of the algorithms and provide a complementary benchmark for the analysis. The use of these images, with known high-quality solutions, facilitates in some cases the assessment of the methods and helps the software development, validation and reproducibility of results. We also propose two quantitative measures of performance for gene ordering. Using these measures, we make a comparison with probably the most used algorithm (due to Eisen and collaborators, PNAS 1998) using a microarray dataset available on the public domain (the complete yeast cell cycle dataset).

Algorithms↗

Accurate prediction of enzyme subfamily class using an adaptive fuzzy k-nearest neighbor method.

Amphiphilic pseudo-amino acid composition (Am-Pse-AAC) with extra sequence-order information is a useful feature for representing enzymes. This study first utilizes the k-nearest neighbor (k-NN) rule to analyze the distribution of enzymes in the Am-Pse-AAC feature space. This analysis indicates the distributions of multiple classes of enzymes are highly overlapped. To cope with the overlap problem, this study proposes an efficient non-parametric classifier for predicting enzyme subfamily class using an adaptive fuzzy r-nearest neighbor (AFK-NN) method, where k and a fuzzy strength parameter m are adaptively specified. The fuzzy membership values of a query sample Q are dynamically determined according to the position of Q and its weighted distances to the k nearest neighbors. Using the same enzymes of the oxidoreductases family for comparisons, the prediction accuracy of AFK-NN is 76.6%, which is better than those of Support Vector Machine (73.6%), the decision tree method C5.0 (75.4%) and the existing covariant-discriminate algorithm (70.6%) using a jackknife test. To evaluate the generalization ability of AFK-NN, the datasets for all six families of entirely sequenced enzymes are established from the newly updated SWISS-PROT and ENZYME database. The accuracy of AFK-NN on the new large-scale dataset of oxidoreductases family is 83.3%, and the mean accuracy of the six families is 92.1%.

Algorithms↗