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VISTA: a classifier for metagenomic subspecies and community state typing of the vaginal microbiome.

Metagenomic community state types (mgCSTs) capture within-species genetic and functional diversity and community structure of the vaginal microbiome, enabling precise links between microbiome composition, function, and health-related risk. VISTA, the Vaginal Inference of Subspecies and Typing Algorithm, is a two-step classifier that assigns mgCSTs to vaginal metagenomes, providing standardized, scalable classifications.

bioinformatics

A fast algorithm for counting the arrangements for packing identical items on a one-dimensional grid with application in DNA-protein and similar interactions.

An algorithm is described, originally developed for use with DNA-protein complexes, which precisely counts the number of possible arrangements for non-overlapping items, each occupying M points, on a lattice of N such points. The algorithm counts the total number of arrangements for a given number of items and can be readily extended to count the number of arrangements which meet an additional criterion. Examples are given of two such classifications and of the application of one of them to a problem in DNA-protein interactions.

Algorithms

Evaluation of contextual analysis for computer classification of cervical smears.

A procedure for automated analysis of cervical smears has been implemented in an image cytometry system. Smears are described exclusively in terms of global and contextual information extracted by pattern-recognition algorithms and represented by a vector of proportions of cellular object types. Linear discriminant functions, based on a Fisher criterion, are derived to classify smears with a cross-section of diagnoses into two broad categories, normal and abnormal. Results obtained from 83 smears indicate 78% correct classification. In contrast to most automated systems, good classification results were obtained in normal smears with benign changes caused by inflammation and with postmenopausal atrophia and in abnormals with mild dysplasia. These findings suggest that contextual analysis may be sensitive to subtle changes in cellular morphology and to progressive patterns of dysplasia. When used with standard isolated cell analysis, contextual analysis may provide additional complementary information for automated cervical prescreening.

Cervix Uteri

Discovery and performance of DNA methylation panels for cancer detection and classification in blood.

Examining DNA in a liquid biopsy for non-invasive cancer detection relies on identifying dilute signal in a high background. This study aims to identify DNA methylation biomarkers for multi-cancer detection. Utilizing large tissue datasets, we apply novel search algorithms to discover confined biomarker panels capable of distinguishing tumor from normal and determining the tissue of origin. We explore the applicability to blood-based testing using targeted methylation sequencing followed by machine learning classification. We present an 8-marker panel, which successfully predicts tumors across 14 types with a 91% average sensitivity, maintaining a low false positive rate (< 0.04%). Additionally, a panel of 39 CpG sites exhibits accuracies ranging from 69% to 98% for identifying tissue of origin. When tested on 114 patient plasma samples (colon, liver, pancreatic, prostate, and stomach cancer), the 8-marker panel obtains an AUC of 0.78 with a 78% sensitivity among 32 early-stage patients (stage I-II), and 60% overall. Using the 39-marker panel in a multi-class classification model selecting only the best match, 54% of tumor samples were on average correctly assigned to the tissue of origin, and up to 80% when allowing more inclusive criteria. Using a limited set of biomarkers, our work contributes to advancing non-invasive cancer diagnostics.

DNA methylation

QRS feature extraction using linear prediction.

This communication proposes a method called linear prediction (a high performant technique in digital speech processing) for analyzing digital ECG signals. There are several significant properties indicating that ECG signals have an important feature in the residual error signal obtained after processing by Durbin's linear prediction algorithm. This communication also indicates that the prediction order need not be more than two for fast arrhythmia detection. The ECG signal classification puts an emphasis on the residual error signal. For each ECG's QRS complex, the feature for recognition is obtained from a nonlinear transformation which transforms every residual error signal to a set of three states pulse-code train relative to the original ECG signal. The pulse-code train has the advantage of easy implementation in digital hardware circuits to achieve automated ECG diagnosis. The algorithm performs very well in feature extraction in arrhythmia detection. Using this method, our studies indicate that the PVC (premature ventricular contraction) detection has at least a 92 percent sensitivity for MIT/BIH arrhythmia database.

Algorithms

[Film digital and texture analysis for digital classification of pulmonary spot opacities].

The study aimed at evaluating the effect of different methods of digitisation of radiographic films on the digital classification of pulmonary opacities. Test sets from the standard of the International Labour Office (ILO) Classification of Radiographs of Pneumoconiosis were prepared by film digitisation using a scanning microdensitometer or a video digitiser based on a personal computer equipped with a real time digitiser board and a vidicon or a Charge Coupled Device (CCD) camera. Seven different algorithms were used for texture analysis resulting in 16 texture parameters for each region. All methods used for texture analysis were independent of the mean grey value level and the size of the image analysed. Classification was performed by discriminant analysis using the classes from the ILO classification. A hit ratio of at least 85% was achieved for a digitisation by scanner digitisation or the vidicon, while the corresponding results of the CCD camera were significantly less good. Classification by texture analysis of opacities of chest X-rays of pneumoconiosis digitised by a personal computer based video digitiser and a vidicon are of equal quality compared to digitisation by a scanning microdensitometer. Correct classification of 90% was achieved via the discribed statistical approach.

Algorithms

A high resolution chromosome image processor for study purposes, NIRS-1000:CHROMO STUDY, and algorithm developing to classify radiation induced aberrations.

Since 1989 we have promoted a project to develop an automated scoring system of radiation induced chromosome aberrations. As a first step, a high resolution image processing system for study purposes, NIRS-1000:CHROMO STUDY, has been developed. It is composed of: (1) CHROMO MARKER whose main purpose is to mark on images to make image data base, (2) CHROMO ALGO whose purpose is algorithm development, and (3) METAPHASE RANKER whose purposes are metaphase finding and ranking with a high power objective lens. However, METAPHASE RANKER is presently under development. The system utilizes a high definition video system so as to realize the best spatial resolution that is achievable with an optical microscope using an objective lens (x 100, numerical aperture 1.4). The video camera has 1024 effective scan lines to realize 0.1 microns sampling on a specimen. The system resolution achieved on the hard copy is less than 0.3 microns on a specimen. A preliminary algorithm has been developed to classify the aberrations on the system using projection information of gray level. The preliminary test results on excellent 10 metaphases show that the correct classification ratio is 92.7%, that the detection rate of the aberrations is 83.3% and that the false positive rate is 6.1%.

Algorithms

A method for automatic classification of large and small myelinated fibre populations in peripheral nerves.

The statistical analysis of morphometric data collected from biopsies of human superficial peroneal nerve is complicated by the heterogeneity of the population of myelinated fibres. In order to make separate statistical analyses of the subpopulations of large and small fibres we have developed a computer program (written in PASCAL) for their automatic separation. The method is based on a dynamic centres clustering algorithm and was applied to the multifactorial space defined by the principal component analysis of the morphometric variables: axonal diameter, myelin sheath thickness, circularity index and g-ratio. The classification technique was applied to measurements obtained from 5 control nerves, and to simulated data, and in each case it gave consistent Gaussian subpopulations with no need for the introduction of supplementary variables.

Algorithms

MegaPX: fast and space-efficient peptide assignment method using IBF-based multi-indexing.

MOTIVATION: A central problem for metaproteomic analysis is the often-unknown taxonomic composition of the analyzed microbiomes. Using a database search, the standard approach requires prior knowledge of which proteins and taxa to include in the protein reference database or to use tailored metagenome-derived databases, which are expensive and error-prone in their generation. A possible strategy to circumvent this database search issue is de novo sequencing, where peptide sequences are directly identified from mass spectra. However, these sequences must still be mapped back to potentially extensive databases. Here, alignment-based approaches enable robust and precise results, with the potential drawback of high memory usage and long run times. RESULTS: We present MegaPX, a software for rapidly classifying de novo peptide sequences against large protein databases. MegaPX implemented as a C++-based tool, uses an alignment-free, k-mer approach as a taxonomic classification method with the possibility of generating mutated reference databases for error-tolerant searching. It uses various algorithms, including interleaved Bloom filters, to efficiently compute approximate membership queries, ensuring fast processing times while querying and indexing large databases in a multi-indexing fashion. We demonstrate the potential of MegaPX by analyzing different samples, including metaproteomics, against extensive reference databases, highlighting its use as a fast screening tool.

Software

Reliability and validity of the Newcastle Scales in relation to ICD-9-classification.

The assessment of endogenous depression by means of the Newcastle Scales (1965, 1971) has been validated by their correlation with biological findings in many previous studies. However, reliability and cross validation studies are lacking for these scales. We found the reliability of the Newcastle Scales to be sufficient or at least moderate in a sample of 70 inpatients with major depression. In order to cross validate both scales, the clinical classification according to ICD-9 and the assessment of the Newcastle Scales have been performed independently in a sample of 112 inpatients with Major Depressive Disorder (RDC). The rate of agreement between clinical diagnosis and classification according to the Newcastle Scales of endogenous depression is only fair. However, a modification of the diagnostic algorithm applied to the items of the Newcastle Scales I (1965) improves the rate of agreement considerably. The Newcastle Scale I turned out to represent a heterogenous concept without sufficient transferability. Modifications of both scales are proposed.

Adult

Echocardiogram analysis in a pattern recognition framework.

Echocardiogram analysis is treated in a pattern recognition framework. Anterior mitral leaflet waveforms are classified for the four-class problem consisting of the classes "normal," "mitral stenosis," "mitral valve prolapse," and "idiopathic hypertrophic subaortic stenosis." In addition, aortic root waveforms and left ventricular wall waveforms are classified for the two-class problem consisting of the classes "normal" and "idiopathic hypertrophic subaortic stenosis." One common method of analysis (Fourier analysis) underlies each classification scheme. Classification accuracy is sufficiently good to warrant the inference that successful automated decision-making based on the algorithms investigated is feasible.

Aortic Valve

Double-judgment psychophysics: problems and solutions.

Many paradigms for comparing identification thresholds with detection thresholds require the observer to make double judgments. We show that these paradigms can produce misleading results because of response biases and attentional shifts. For example, the subject's response bias plus correlated noise can mimic inhibition between channels. Some of these same problems can affect single-judgment paradigms. A detailed analysis of the double-judgment forced-choice paradigm reveals that there are a multiplicity of optimal strategies, some of which enhance identification over detection. Several improved analysis techniques for minimizing the effects of cognitive factors are proposed for both the double-judgment forced-choice paradigm and the double-judgment rating-scale paradigm. A classification scheme for distinguishing different types of interactions and correlations is developed. When the new rating-scale algorithm is applied to the detection of well-separated spatial frequencies, substantial masking but negligible inhibition is found. The rating-scale paradigm is shown to be useful in revealing not only the sensitivity and the interactions of the underlying mechanisms but also the observer's information-processing strategies.

Attention

Automated Classification of Lymphoma Subtypes From Histopathological Images Using a U-Net Deep Learning Model: Comparative Evaluation Study.

BACKGROUND: Accurate classification and grading of lymphoma subtypes are essential for treatment planning. Traditional diagnostic methods face challenges of subjectivity and inefficiency, highlighting the need for automated solutions based on deep learning techniques. OBJECTIVE: This study aimed to investigate the application of deep learning technology, specifically the U-Net model, in classifying and grading lymphoma subtypes to enhance diagnostic precision and efficiency. METHODS: In this study, the U-Net model was used as the primary tool for image segmentation integrated with attention mechanisms and residual networks for feature extraction and classification. A total of 620 high-quality histopathological images representing 3 major lymphoma subtypes were collected from The Cancer Genome Atlas and the Cancer Imaging Archive. All images underwent standardized preprocessing, including Gaussian filtering for noise reduction, histogram equalization, and normalization. Data augmentation techniques such as rotation, flipping, and scaling were applied to improve the model's generalization capability. The dataset was divided into training (70%), validation (15%), and test (15%) subsets. Five-fold cross-validation was used to assess model robustness. Performance was benchmarked against mainstream convolutional neural network architectures, including fully convolutional network, SegNet, and DeepLabv3+. RESULTS: The U-Net model achieved high segmentation accuracy, effectively delineating lesion regions and improving the quality of input for classification and grading. The incorporation of attention mechanisms further improved the model's ability to extract key features, whereas the residual structure of the residual network enhanced classification accuracy for complex images. In the test set (N=1250), the proposed fusion model achieved an accuracy of 92% (1150/1250), a sensitivity of 91.04% (1138/1250), a specificity of 89.04% (1113/1250), and an F1-score of 90% (1125/1250) for the classification of the 3 lymphoma subtypes, with an area under the receiver operating characteristic curve of 0.95 (95% CI 0.93-0.97). The high sensitivity and specificity of the model indicate strong clinical applicability, particularly as an assistive diagnostic tool. CONCLUSIONS: Deep learning techniques based on the U-Net architecture offer considerable advantages in the automated classification and grading of lymphoma subtypes. The proposed model significantly improved diagnostic accuracy and accelerated pathological evaluation, providing efficient and precise support for clinical decision-making. Future work may focus on enhancing model robustness through integration with advanced algorithms and validating performance across multicenter clinical datasets. The model also holds promise for deployment in digital pathology platforms and artificial intelligence-assisted diagnostic workflows, improving screening efficiency and promoting consistency in pathological classification.

Humans

GeomeTRe: accurate calculation of geometrical descriptors of tandem repeat proteins.

MOTIVATION: Structured tandem repeat proteins (STRPs) are characterized by preserved structural motifs arranged in a modular way. The structural and functional diversity of STRPs makes them particularly important for studying evolution and novel structure-function relationships, and ultimately for designing new synthetic proteins with specific functions. One crucial aspect of their classification is the estimation of geometrical parameters, which can provide better insight into their properties and the relationship between the spatial arrangement of repeated units and protein function. Calculating geometric descriptors for STRPs is challenging because naturally occurring repeats are not "perfect" and often contain insertions and deletions. Existing tools for predicting structural symmetry work well on simple cases but often fail for most natural proteins. RESULTS: Here, we present GeomeTRe, an algorithm that calculates geometrical descriptors such as curvature (yaw), twist (roll), and pitch for a protein structure with known repeat unit positions. The algorithm simulates the movement of consecutive units, identifies rotational axes, and calculates the corresponding Tait-Bryan angles. GeomeTRe's parameters can enhance STRP annotation and classification by identifying variations in geometric arrangements among different functional groups. The package is fast and suitable for processing large protein structure datasets when repeat region information (e.g. from RepeatsDB) is available. AVAILABILITY AND IMPLEMENTATION: GeomeTRe is available as a Python package; source code and documentation can be found at https://github.com/BioComputingUP/GeomeTRe.

Algorithms

Computer interpreted fetal electroencephalogram: sharp wave detection and classification of infants for one year neurological outcome.

The presence of visually discernible sharp waves (SWs) in the fetal electroencephalogram (FEEG) has been found to be associated with abnormal neurological infant outcome, but no method of programmed SW detection for FEEG was available. In order to develop an algorithm for SW detection, the first and second derivatives for visually identified SWs and non-SWs were examined and five random variables chosen for discriminant function analysis (DFA). The resulting equation, incorporated into program logic along with logic for artifact rejection, produced classifications from 85% to 89% consistent with visual identifications, suggesting that the number of SWs/epoch (NSW) corresponds with visually identified SWs. In addition, in 61 cases using a threshold for NSW derived by DFA, computer recognized SWs were found to be significantly related to the overall visual interpretation of the tracings (P less than 0.005). Finally, NSW alone produced correct classification of 65.5% of infants for 1 year neurological outcome. The overall consistency was increased to as high as 80% using additional FEEG and neonatal data. These findings imply that some forms of brain damage are present before birth and can be detected during labor using FEEG.

Brain Diseases