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Refinement of generated fuzzy production rules by using a fuzzy neural network.

Fuzzy production rules (FPRs) have been used for years to capture and represent fuzzy, vague, imprecise and uncertain domain knowledge in many fuzzy systems. There have been a lot of researches on how to generate or obtain FPRs. There exist two methods to obtain FPRs. One is by painstakingly, repeatedly and time-consuming interviewing domain experts to extract the domain knowledge. The other is by using some machine learning techniques to generate and extract FPRs from some training samples. These extracted rules, however, are found to be nonoptimal and sometimes redundant. Furthermore, these generated rules suffer from the problem of low accuracy of classifying or recognizing unseen examples. The reasons for having these problems are 1) the FPRs generated are not powerful enough to represent the domain knowledge, 2) the techniques used to generate FPRs are pre-matured, ad-hoc or may not be suitable for the problem, and 3) further refinement of the extracted rules has not been done. In this paper we look into the solutions of the above problems by 1) enhancing the representation power of FPRs by including local and global weights, 2) developing a fuzzy neural network (FNN) with enhanced learning algorithm, and 3) using this FNN to refine the local and global weights of FPRs. By experimenting our method with some existing benchmark examples, the proposed method is found to have high accuracy in classifying unseen samples without increasing the number of the FPRs extracted and the time required to consult with domain experts is greatly reduced.

Journal Article↗

Accurate identification of alternatively spliced exons using support vector machine.

MOTIVATION: Alternative splicing is a major component of the regulatory action on mammalian transcriptomes. It is estimated that over half of all human genes have more than one splice variant. Previous studies have shown that alternatively spliced exons possess several features that distinguish them from constitutively spliced ones. Recently, we have demonstrated that such features can be used to distinguish alternative from constitutive exons. In the current study, we used advanced machine learning methods to generate robust classifier of alternative exons. RESULTS: We extracted several hundred local sequence features of constitutive as well as alternative exons. Using feature selection methods we find seven attributes that are dominant for the task of classification. Several less informative features help to slightly increase the performance of the classifier. The classifier achieves a true positive rate of 50% for a false positive rate of 0.5%. This result enables one to reliably identify alternatively spliced exons in exon databases that are believed to be dominated by constitutive exons.

Algorithms↗

Deep assessment of machine learning techniques using patient treatment in acute abdominal pain in children.

Learning from patient records may aid knowledge acquisition and decision making. Existing inductive machine learning (ML) systems such us NewId, CN2, C4.5 and AQ15 learn from past case histories using symbolic and/or numeric values. These systems learn symbolic rules (IF... THEN like) which link an antecedent set of clinical factors to a consequent class or decision. This paper compares the learning performance of alternative ML systems with each other and with respect to a novel approach using logic minimization, called LML, to learn from data. Patient cases were taken from the archives of the Paediatric Surgery Clinic of the University Hospital of Crete, Heraklion, Greece. Comparison of ML system performance is based both on classification accuracy and on informal expert assessment of learned knowledge.

Abdomen, Acute↗

An interpretable deep learning framework uncovers features governing CRISPR-Cas9 genome-editing efficiency.

MOTIVATION: CRISPR-Cas9 genome-editing efficiency is strongly influenced by the sequence composition and positional context of single-guide RNAs (sgRNAs). Although numerous deep learning-based models have been developed to predict Cas9 efficiency from sgRNA sequences, most operate as black boxes, offering limited insight into the sequence determinants underlying Cas9 activity. In addition, previous studies often overlook how the positional context of sequence motifs within sgRNAs influences their effects on Cas9 binding or cleavage. RESULTS: We introduce DeepCC9, an interpretable machine learning framework that combines explicit sequence feature extraction with a residual block-based deep architecture to improve interpretability and identify composition- and position-based motifs governing Cas9 genome-editing efficiency. We applied this method to multiple Cas9 variant datasets, achieving superior predictive performance compared with existing methods while enabling direct interpretation of sequence motifs and their positional effects. Our analysis uncovered 74 sequence motifs enriched or depleted at specific positions within sgRNAs and strongly associated with Cas9 efficiency, providing mechanistic insight into sequence features that influence guide performance. Together, these results establish DeepCC9 as a generalizable and interpretable framework for modeling sequence-function relationships and advancing the understanding of the sequence determinants underlying CRISPR-Cas9 genome editing. AVAILABILITY AND IMPLEMENTATION: The authors have implemented their algorithm in the Python programming language (version 3.X), which is accessible using (https://zenodo.org/records/20073890).

Deep Learning↗

Treemble: a graphical tool to generate Newick strings from phylogenetic tree images.

SUMMARY: Phylogenetic trees are ubiquitous and central to biology, but most published trees are available only as visual diagrams and not in the machine-readable Newick format. There are, thus, thousands of published trees in the scientific literature that are unavailable for follow-up analyses, comparisons, and supertree construction. Experts can easily read such diagrams, but the manual construction of a Newick string from a diagram is laborious, error-prone, and time-consuming. Previous attempts to semi-automate the reading of tree images relied on image processing techniques. These often encounter difficulties as typical published tree diagrams contain various graphical elements and annotations that overlap the branches, such as error bars on internal nodes. Here we introduce Treemble, a user-friendly desktop application for generating Newick strings from tree images. The user simply clicks to mark node locations, assisted by a deep learning-based node detection tool, and Treemble algorithmically assembles the tree from the node coordinates alone. Treemble also facilitates the automatic reading of tip name labels and can be used for both rectangular and circular trees. AVAILABILITY AND IMPLEMENTATION: Treemble is a native desktop application for macOS and Windows and is freely available, with documentation, at treemble.org. Source code is available at github.com/John-Allard/Treemble. The trained node detection model is available at huggingface.co/John-Allard/treemble-1.

Phylogeny↗

Geometrical properties of nu support vector machines with different norms.

By employing the L1 or Linfinity norms in maximizing margins, support vector machines (SVMs) result in a linear programming problem that requires a lower computational load compared to SVMs with the L2 norm. However, how the change of norm affects the generalization ability of SVMs has not been clarified so far except for numerical experiments. In this letter, the geometrical meaning of SVMs with the Lp norm is investigated, and the SVM solutions are shown to have rather little dependency on p.

Algorithms↗

Application of machine learning in SNP discovery.

BACKGROUND: Single nucleotide polymorphisms (SNP) constitute more than 90% of the genetic variation, and hence can account for most trait differences among individuals in a given species. Polymorphism detection software PolyBayes and PolyPhred give high false positive SNP predictions even with stringent parameter values. We developed a machine learning (ML) method to augment PolyBayes to improve its prediction accuracy. ML methods have also been successfully applied to other bioinformatics problems in predicting genes, promoters, transcription factor binding sites and protein structures. RESULTS: The ML program C4.5 was applied to a set of features in order to build a SNP classifier from training data based on human expert decisions (True/False). The training data were 27,275 candidate SNP generated by sequencing 1973 STS (sequence tag sites) (12 Mb) in both directions from 6 diverse homozygous soybean cultivars and PolyBayes analysis. Test data of 18,390 candidate SNP were generated similarly from 1359 additional STS (8 Mb). SNP from both sets were classified by experts. After training the ML classifier, it agreed with the experts on 97.3% of test data compared with 7.8% agreement between PolyBayes and experts. The PolyBayes positive predictive values (PPV) (i.e., fraction of candidate SNP being real) were 7.8% for all predictions and 16.7% for those with 100% posterior probability of being real. Using ML improved the PPV to 84.8%, a 5- to 10-fold increase. While both ML and PolyBayes produced a similar number of true positives, the ML program generated only 249 false positives as compared to 16,955 for PolyBayes. The complexity of the soybean genome may have contributed to high false SNP predictions by PolyBayes and hence results may differ for other genomes. CONCLUSION: A machine learning (ML) method was developed as a supplementary feature to the polymorphism detection software for improving prediction accuracies. The results from this study indicate that a trained ML classifier can significantly reduce human intervention and in this case achieved a 5-10 fold enhanced productivity. The optimized feature set and ML framework can also be applied to all polymorphism discovery software. ML support software is written in Perl and can be easily integrated into an existing SNP discovery pipeline.

Algorithms↗

Clustering time-varying gene expression profiles using scale-space signals.

The functional state of an organism is determined largely by the pattern of expression of its genes. The analysis of gene expression data from gene chips has primarily revolved around clustering and classification of the data using machine learning techniques based on the intensity of expression alone with the time-varying pattern mostly ignored. In this paper, we present a pattern recognition-based approach to capturing similarity by finding salient changes in the time-varying expression patterns of genes. Such changes can give clues about important events, such as gene regulation by cell-cycle phases, or even signal the onset of a disease. Specifically, we observe that dissimilarity between time series is revealed by the sharp twists and bends produced in a higher-dimensional curve formed from the constituent signals. Scale-space analysis is used to detect the sharp twists and turns and their relative strength with respect to the component signals is estimated to form a shape similarity measure between time profiles. A clustering algorithm is presented to cluster gene profiles using the scale-space distance as a similarity metric. Multi-dimensional curves formed from time series within clusters are used as cluster prototypes or indexes to the gene expression database, and are used to retrieve the functionally similar genes to a query gene profile. Extensive comparison of clustering using scale-space distance in comparison to traditional Euclidean distance is presented on the yeast genome database.

Algorithms↗

Proteomic mass spectra classification using decision tree based ensemble methods.

MOTIVATION: Modern mass spectrometry allows the determination of proteomic fingerprints of body fluids like serum, saliva or urine. These measurements can be used in many medical applications in order to diagnose the current state or predict the evolution of a disease. Recent developments in machine learning allow one to exploit such datasets, characterized by small numbers of very high-dimensional samples. RESULTS: We propose a systematic approach based on decision tree ensemble methods, which is used to automatically determine proteomic biomarkers and predictive models. The approach is validated on two datasets of surface-enhanced laser desorption/ionization time of flight measurements, for the diagnosis of rheumatoid arthritis and inflammatory bowel diseases. The results suggest that the methodology can handle a broad class of similar problems.

Algorithms↗

Image transform bootstrapping and its applications to semantic scene classification.

The performance of an exemplar-based scene classification system depends largely on the size and quality of its set of training exemplars, which can be limited in practice. In addition, in nontrivial data sets, variations in scene content as well as distracting regions may exist in many testing images to prohibit good matches with the exemplars. Various boosting schemes have been proposed in machine learning, focusing on the feature space. We introduce the novel concept of image-transform bootstrapping using transforms in the image space to address such issues. In particular, three major schemes are described for exploiting this concept to augment training, testing, and both. We have successfully applied it to three applications of increasing difficulty: sunset detection, outdoor scene classification, and automatic image orientation detection. It is shown that appropriate transforms and meta-classification methods can be selected to boost performance according to the domain of the problem and the features/classifier used.

Algorithms↗

Predicting protein secondary structure by a support vector machine based on a new coding scheme.

Protein structure prediction is one of the most important problems in modern computational biology. Protein secondary structure prediction is a key step in prediction of protein tertiary structure. There have emerged many methods based on machine learning techniques, such as neural networks (NN) and support vector machine (SVM) etc., to focus on the prediction of the secondary structures. In this paper, a new method was proposed based on SVM. Different from the existing methods, this method takes into account of the physical-chemical properties and structure properties of amino acids. When tested on the most popular dataset CB513, it achieved a Q(3) accuracy of 0.7844, which illustrates that it is one of the top range methods for protein of secondary structure prediction.

Algorithms↗

Neural networks, nativism, and the plausibility of constructivism.

Recent interest in PDP (parallel distributed processing) models is due in part to the widely held belief that they challenge many of the assumptions of classical cognitive science. In the domain of language acquisition, for example, there has been much interest in the claim that PDP models might undermine nativism. Related arguments based on PDP learning have also been given against Fodor's anti-constructivist position--a position that has contributed to the widespread dismissal of constructivism. A limitation of many of the claims regarding PDP learning, however, is that the principles underlying this learning have not been rigorously characterized. In this paper, I examine PDP models from within the framework of Valiant's PAC (probably approximately correct) model of learning, now the dominant model in machine learning, and which applies naturally to neural network learning. From this perspective, I evaluate the implications of PDP models for nativism and Fodor's influential anti-constructivist position. In particular, I demonstrate that, contrary to a number of claims, PDP models are nativist in a robust sense. I also demonstrate that PDP models actually serve as a good illustration of Fodor's anti-constructivist position. While these results may at first suggest that neural network models in general are incapable of the sort of concept acquisition that is required to refute Fodor's anti-constructivist position, I suggest that there is an alternative form of neural network learning that demonstrates the plausibility of constructivism. This alternative form of learning is a natural interpretation of the constructivist position in terms of neural network learning, as it employs learning algorithms that incorporate the addition of structure in addition to weight modification schemes. By demonstrating that there is a natural and plausible interpretation of constructivism in terms of neural network learning, the position that nativism is the only plausible model of acquisition can no longer be defended. Indeed, I briefly discuss a number of learning-theoretic reasons indicating that constructivist models so characterized uniquely possess a number of important learning characteristics.

Cognition↗

Rapid identification of closely related muscle foods by vibrational spectroscopy and machine learning.

Muscle foods are an integral part of the human diet and during the last few decades consumption of poultry products in particular has increased significantly. It is important for consumers, retailers and food regulatory bodies that these products are of a consistently high quality, authentic, and have not been subjected to adulteration by any lower-grade material either by accident or for economic gain. A variety of methods have been developed for the identification and authentication of muscle foods. However, none of these are rapid or non-invasive, all are time-consuming and difficulties have been encountered in discriminating between the commercially important avian species. Whilst previous attempts have been made to discriminate between muscle foods using infrared spectroscopy, these have had limited success, in particular regarding the closely related poultry species, chicken and turkey. Moreover, this study includes novel data since no attempts have been made to discriminate between both the species and the distinct muscle groups within these species, and this is the first application of Raman spectroscopy to the study of muscle foods. Samples of pre-packed meat and poultry were acquired and FT-IR and Raman measurements taken directly from the meat surface. Qualitative interpretation of FT-IR and Raman spectra at the species and muscle group levels were possible using discriminant function analysis. Genetic algorithms were used to elucidate meaningful interpretation of FT-IR results in (bio)chemical terms and we show that specific wavenumbers, and therefore chemical species, were discriminatory for each type (species and muscle) of poultry sample. We believe that this approach would aid food regulatory bodies in the rapid identification of meat and poultry products and shows particular potential for rapid assessment of food adulteration.

Algorithms↗

Vessel enhancement in digital X-ray angiographic sequences by temporal statistical learning.

In this paper, we present a vessel enhancement method, SVM temporal filtering (STF), for X-ray angiographic (XA) images using Support Vector Machine (SVM). We show that the linear SVM applied to vessel enhancement can be regarded as a matched linear filter optimizing the contrast-to-noise ratio in XA images. We propose a non-linear kernel function for the SVM leading to good enhancement with noisy, varying grey-level dynamics at vessel pixels. One key advantage over the matched filters is that an optimal filter is learnt from images, not estimated at design stage. Results on clinical XA images show that learning-based enhancement achieves better results compared to simple subtraction and other image stacking methods.

Algorithms↗

Comprehensible evaluation of prognostic factors and prediction of wound healing.

We analyzed the data of a controlled clinical study of the chronic wound healing acceleration as a result of electrical stimulation. The study involved a conventional conservative treatment, sham treatment, biphasic pulsed current, and direct current electrical stimulation. Data was collected over 10 years and suffices for an analysis with machine learning methods. So far, only a limited number of studies have investigated the wound and patient attributes which affect the chronic wound healing. There is none to our knowledge to include treatment attributes. The aims of our study are to determine effects of the wound, patient and treatment attributes on the wound healing process and to propose a system for prediction of the wound healing rate. First we analyzed which wound and patient attributes play a predominant role in the wound healing process and investigated a possibility to predict the wound healing rate at the beginning of the treatment based on the initial wound, patient and treatment attributes. Later we tried to enhance the wound healing rate prediction accuracy by predicting it after a few weeks of the wound healing follow-up. Using the attribute estimation algorithms ReliefF and RReliefF we obtained a ranking of the prognostic factors which was comprehensible to experts. We used regression and classification trees to build models for prediction of the wound healing rate. The obtained results are encouraging and may form a basis for an expert system for the chronic wound healing rate prediction. If the wound healing rate is known, then the provided information can help to formulate the appropriate treatment decisions and orient resources towards individuals with poor prognosis.

Algorithms↗

The generalized LASSO.

In the last few years, the support vector machine (SVM) method has motivated new interest in kernel regression techniques. Although the SVM has been shown to exhibit excellent generalization properties in many experiments, it suffers from several drawbacks, both of a theoretical and a technical nature: the absence of probabilistic outputs, the restriction to Mercer kernels, and the steep growth of the number of support vectors with increasing size of the training set. In this paper, we present a different class of kernel regressors that effectively overcome the above problems. We call this approach generalized LASSO regression. It has a clear probabilistic interpretation, can handle learning sets that are corrupted by outliers, produces extremely sparse solutions, and is capable of dealing with large-scale problems. For regression functionals which can be modeled as iteratively reweighted least-squares (IRLS) problems, we present a highly efficient algorithm with guaranteed global convergence. This defies a unique framework for sparse regression models in the very rich class of IRLS models, including various types of robust regression models and logistic regression. Performance studies for many standard benchmark datasets effectively demonstrate the advantages of this model over related approaches.

Algorithms↗

A computer aided system for systematic production and revision of sequence patterns.

We used two complementary fields, object-oriented databases and machine learning, to produce and revise a set of protein sequence patterns. In a first stage, we show that object-oriented query languages are well suited for the production of patterns as well as for the interpretation of the biological function of new (uncharacterized) sequences. In a second stage, a classification is built from the set of sequences according to the pattern matches. This classification may be criticized by a specific analysis method, which yields back to revise sequences and patterns. In our application, we have used concept lattices as a classification method and sequence multiple alignment for criticism.

Algorithms↗

Learning kernels from biological networks by maximizing entropy.

MOTIVATION: The diffusion kernel is a general method for computing pairwise distances among all nodes in a graph, based on the sum of weighted paths between each pair of nodes. This technique has been used successfully, in conjunction with kernel-based learning methods, to draw inferences from several types of biological networks. RESULTS: We show that computing the diffusion kernel is equivalent to maximizing the von Neumann entropy, subject to a global constraint on the sum of the Euclidean distances between nodes. This global constraint allows for high variance in the pairwise distances. Accordingly, we propose an alternative, locally constrained diffusion kernel, and we demonstrate that the resulting kernel allows for more accurate support vector machine prediction of protein functional classifications from metabolic and protein-protein interaction networks. AVAILABILITY: Supplementary results and data are available at noble.gs.washington.edu/proj/maxent

Algorithms↗