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Quantitative analysis of computed tomography scans of the lungs for the diagnosis of pulmonary emphysema. A validation study of a semiautomated contour detection technique.

RATIONALE AND OBJECTIVES: To develop an analytic software package based on automated contour detection for the objective and reproducible assessment of emphysema from computed tomography (CT) scans. METHODS: A semiautomated technique was developed for the definition of lung contours in CT cross-sections followed by the assessment of pulmonary CT parameters describing the disease state. For 78 images, the semiautomated contour detection was performed and compared with contours drawn by an experienced radiologist by calculating the systematic area difference (bias) and differences in pulmonary CT parameters such as the mean lung density (MLD). In addition, intraobserver and interobserver variabilities were determined in a subset of 15 images. RESULTS: The areas enclosed by the semiautomatically detected contours were slightly larger than the manual ones (bias < 2.1%). The biases in the observer studies were smaller in the semiautomated versus the manual case (0.3% vs. 1.3%). The standard deviation of the MLD differences with a manual analysis was larger by a factor of five than in the semiautomated case. On average, manual analysis required 2 minutes, 18 seconds per lung; this time was reduced to 11.5 to 29 seconds with the semiautomated approach, depending on the respiration state. CONCLUSIONS: The semiautomated approach is preferred over the manual approach because of its higher consistency and its shorter analysis time.

Adult↗

A graphical model approach to automated classification of protein subcellular location patterns in multi-cell images.

BACKGROUND: Knowledge of the subcellular location of a protein is critical to understanding how that protein works in a cell. This location is frequently determined by the interpretation of fluorescence microscope images. In recent years, automated systems have been developed for consistent and objective interpretation of such images so that the protein pattern in a single cell can be assigned to a known location category. While these systems perform with nearly perfect accuracy for single cell images of all major subcellular structures, their ability to distinguish subpatterns of an organelle (such as two Golgi proteins) is not perfect. Our goal in the work described here was to improve the ability of an automated system to decide which of two similar patterns is present in a field of cells by considering more than one cell at a time. Since cells displaying the same location pattern are often clustered together, considering multiple cells may be expected to improve discrimination between similar patterns. RESULTS: We describe how to take advantage of information on experimental conditions to construct a graphical representation for multiple cells in a field. Assuming that a field is composed of a small number of classes, the classification accuracy can be improved by allowing the computed probability of each pattern for each cell to be influenced by the probabilities of its neighboring cells in the model. We describe a novel way to allow this influence to occur, in which we adjust the prior probabilities of each class to reflect the patterns that are present. When this graphical model approach is used on synthetic multi-cell images in which the true class of each cell is known, we observe that the ability to distinguish similar classes is improved without suffering any degradation in ability to distinguish dissimilar classes. The computational complexity of the method is sufficiently low that improved assignments of classes can be obtained for fields of twelve cells in under 0.04 second on a 1600 megahertz processor. CONCLUSION: We demonstrate that graphical models can be used to improve the accuracy of classification of subcellular patterns in multi-cell fluorescence microscope images. We also describe a novel algorithm for inferring classes from a graphical model. The performance and speed suggest that the method will be particularly valuable for analysis of images from high-throughput microscopy. We also anticipate that it will be useful for analyzing the mixtures of cell types typically present in images of tissues. Lastly, we anticipate that the method can be generalized to other problems.

Algorithms↗

Automated protein NMR resonance assignments.

NMR resonance peak assignment is one of the key steps in solving an NMR protein structure. The assignment process links resonance peaks to individual residues of the target protein sequence, providing the prerequisite for establishing intra- and inter-residue spatial relationships between atoms. The assignment process is tedious and time-consuming, which could take many weeks. Though there exist a number of computer programs to assist the assignment process, many NMR labs are still doing the assignments manually to ensure quality. This paper presents (1) a new scoring system for mapping spin systems to residues, (2) an automated adjacency information extraction procedure from NMR spectra, and (3) a very fast assignment algorithm based on our previous proposed greedy filtering method and a maximum matching algorithm to automate the assignment process. The computational tests on 70 instances of (pseudo) experimental NMR data of 14 proteins demonstrate that the new score scheme has much better discerning power with the aid of adjacency information between spin systems simulated across various NMR spectra. Typically, with automated extraction of adjacency information, our method achieves nearly complete assignments for most of the proteins. The experiment shows very promising perspective that the fast automated assignment algorithm together with the new score scheme and automated adjacency extraction may be ready for practical use.

Algorithms↗

Maximum A posteriori classification of DNA structure from sequence information.

We introduce an algorithm, LLLAMA, which combines simple pattern recognizers into a general method for estimating the entropy of a sequence. Each pattern recognizer exploits a partial match between subsequences to build a model of the sequence. Since the primary features of interest in biological sequence domains are subsequences with small variations in exact composition, LLLAMA is particularly suited to such domains. We describe two methods, LLLAMA-length and LLLAMA-alone, which use this entropy estimate to perform maximum a posteriori classification. We apply these methods to several problems in three-dimensional structure classification of short DNA sequences. The results include a surprisingly low 3.6% error rate in predicting helical conformation of oligonucleotides. We compare our results to those obtained using more traditional methods for automated generation of classifiers.

Algorithms↗

Evaluation of pattern recognition rules for the apex of the heart.

The observer variability and accuracy of rules for the automatic recognition of the left ventricular (LV) apex are reported. To form a data base for examining this problem 18 co-workers were asked to independently identify the apex of 79 left ventriculograms (LVgrams) in the 30-degree right anterior oblique projection at end-disastole (ED) and end-systole (ES), and to assign a confidence score from 0% to 100% for each apex. The group consisted of five clinical cardiologists (G1), six trained analysts (G2), and seven other experienced observers (G3). The LVgrams were selected to include those from 31 normal individuals and those from 48 patients with mixed akinesis/dykinesis as coded by conventional scoring techniques. There was no significant difference in the confidence for the ED vs ES apices. However, confidence of G1 was significantly lower than that of G2. The standard deviation in the observer-detected apex correlated (r = -0.92) with the mean observer confidence, which suggests a basis for quantifying "confidence" in the automated apex detection. The apex determined with respect to the superior aspect of the aortic valve proved superior to all other tested methods. the concept of "peakedness index" is introduced and used to estimate observer variability.

Adult↗

Massive-training artificial neural network (MTANN) for reduction of false positives in computer-aided detection of polyps: Suppression of rectal tubes.

One of the limitations of the current computer-aided detection (CAD) of polyps in CT colonography (CTC) is a relatively large number of false-positive (FP) detections. Rectal tubes (RTs) are one of the typical sources of FPs because a portion of a RT, especially a portion of a bulbous tip, often exhibits a cap-like shape that closely mimics the appearance of a small polyp. Radiologists can easily recognize and dismiss RT-induced FPs; thus, they may lose their confidence in CAD as an effective tool if the CAD scheme generates such "obvious" FPs due to RTs consistently. In addition, RT-induced FPs may distract radiologists from less common true positives in the rectum. Therefore, removal RT-induced FPs as well as other types of FPs is desirable while maintaining a high sensitivity in the detection of polyps. We developed a three-dimensional (3D) massive-training artificial neural network (MTANN) for distinction between polyps and RTs in 3D CTC volumetric data. The 3D MTANN is a supervised volume-processing technique which is trained with input CTC volumes and the corresponding "teaching" volumes. The teaching volume for a polyp contains a 3D Gaussian distribution, and that for a RT contains zeros for enhancement of polyps and suppression of RTs, respectively. For distinction between polyps and nonpolyps including RTs, a 3D scoring method based on a 3D Gaussian weighting function is applied to the output of the trained 3D MTANN. Our database consisted of CTC examinations of 73 patients, scanned in both supine and prone positions (146 CTC data sets in total), with optical colonoscopy as a reference standard for the presence of polyps. Fifteen patients had 28 polyps, 15 of which were 5-9 mm and 13 were 10-25 mm in size. These CTC cases were subjected to our previously reported CAD scheme that included centerline-based segmentation of the colon, shape-based detection of polyps, and reduction of FPs by use of a Bayesian neural network based on geometric and texture features. Application of this CAD scheme yielded 96.4% (27/28) by-polyp sensitivity with 3.1 (224/73) FPs per patient, among which 20 FPs were caused by RTs. To eliminate the FPs due to RTs and possibly other normal structures, we trained a 3D MTANN with ten representative polyps and ten RTs, and applied the trained 3D MTANN to the above CAD true- and false-positive detections. In the output volumes of the 3D MTANN, polyps were represented by distributions of bright voxels, whereas RTs and other normal structures partly similar to RTs appeared as darker voxels, indicating the ability of the 3D MTANN to suppress RTs as well as other normal structures effectively. Application of the 3D MTANN to the CAD detections showed that the 3D MTANN eliminated all RT-induced 20 FPs, as well as 53 FPs due to other causes, without removal of any true positives. Overall, the 3D MTANN was able to reduce the FP rate of the CAD scheme from 3.1 to 2.1 FPs per patient (33% reduction), while the original by-polyp sensitivity of 96.4% was maintained.

Algorithms↗

Automated protein function prediction--the genomic challenge.

Overwhelmed with genomic data, biologists are facing the first big post-genomic question--what do all genes do? First, not only is the volume of pure sequence and structure data growing, but its diversity is growing as well, leading to a disproportionate growth in the number of uncharacterized gene products. Consequently, established methods of gene and protein annotation, such as homology-based transfer, are annotating less data and in many cases are amplifying existing erroneous annotation. Second, there is a need for a functional annotation which is standardized and machine readable so that function prediction programs could be incorporated into larger workflows. This is problematic due to the subjective and contextual definition of protein function. Third, there is a need to assess the quality of function predictors. Again, the subjectivity of the term 'function' and the various aspects of biological function make this a challenging effort. This article briefly outlines the history of automated protein function prediction and surveys the latest innovations in all three topics.

Algorithms↗

Automated diagnostic systems with diverse and composite features for Doppler ultrasound signals.

In this paper, we present the automated diagnostic systems for Doppler ultrasound signals classification with diverse and composite features and determine their accuracies. We compared the classification accuracies of six different classifiers, namely multilayer perceptron neural network (MLP), combined neural network (CNN), mixture of experts (ME), modified mixture of experts (MME), probabilistic neural network (PNN), and support vector machine (SVM), which were trained on diverse or composite features. The present study was conducted with the purpose of answering the question of whether the automated diagnostic systems improve the capability of classification of ophthalmic arterial (OA) and internal carotid arterial (ICA) Doppler signals. Our research demonstrated that the SVM trained on composite feature and the MME trained on diverse features achieved accuracy rates which were higher than that of the other automated diagnostic systems.

Algorithms↗

Automatic detection and segmentation of robot-assisted surgical motions.

Robotic surgical systems such as Intuitive Surgical's da Vinci system provide a rich source of motion and video data from surgical procedures. In principle, this data can be used to evaluate surgical skill, provide surgical training feedback, or document essential aspects of a procedure. If processed online, the data can be used to provide context-specific information or motion enhancements to the surgeon. However, in every case, the key step is to relate recorded motion data to a model of the procedure being performed. This paper examines our progress at developing techniques for "parsing" raw motion data from a surgical task into a labelled sequence of surgical gestures. Our current techniques have achieved >90% fully automated recognition rates on 15 datasets.

Artificial Intelligence↗

Ellipse test for the reduction of false positive signals in automated cytology.

One of the major problems in automated cytology is the elimination of false positive 'abnormal cell' alarms caused by objects such as overlapping cell pairs, leukocyte clusters, etc. The paper describes an algorithm for the separation of images of abnormal cell nuclei and non=nuclear objects in computer image analysis systems for automated cytology. The algorithm involves the measurement of the agreement between the object outline and a computer ellipse of equal area, aspect ratio and orientation. Results obtained with the CERVISCAN experimental computer image analysis system show that the algorithm gives good discrimination between abnormal cell nuclei and typical non-nuclear objects found in cervical scrape specimens prepared specially for automated analysis.

Cell Nucleus↗

Sequential characterization of atrial tachyarrhythmias based on ECG time-frequency analysis.

A new method for characterization of atrial arrhythmias is presented which is based on the time-frequency distribution of an atrial electrocardiographic signal. A set of parameters are derived which describe fundamental frequency, amplitude, shape, and signal-to-noise ratio. The method uses frequency-shifting of an adaptively updated spectral profile, representing the shape of the atrial waveforms, in order to match each new spectrum of the distribution. The method tracks how well the spectral profile fits each spectrum as well as if a valid atrial signal is present. The results are based on the analysis of a learning database with signals from 40 subjects, of which 24 have atrial arrhythmias, and an evaluation database with 211 patients diagnosed with atrial fibrillation. It is shown that the method robustly estimates fibrillation frequency and amplitude and produces spectral profiles with narrower peaks and more discernible harmonics when compared to the conventional power spectrum. The results suggest that a rather strong correlation exist between atrial fibrillation frequency and f wave shape. The developed set of parameters may be used as a basis for automated classification of different atrial rhythms.

Algorithms↗

Spectral Repeat Finder (SRF): identification of repetitive sequences using Fourier transformation.

MOTIVATION: Repetitive DNA sequences, besides having a variety of regulatory functions, are one of the principal causes of genomic instability. Understanding their origin and evolution is of fundamental importance for genome studies. The identification of repeats and their units helps in deducing the intra-genomic dynamics as an important feature of comparative genomics. A major difficulty in identification of repeats arises from the fact that the repeat units can be either exact or imperfect, in tandem or dispersed, and of unspecified length. RESULTS: The Spectral Repeat Finder program circumvents these problems by using a discrete Fourier transformation to identify significant periodicities present in a sequence. The specific regions of the sequence that contribute to a given periodicity are located through a sliding window analysis, and an exact search method is then used to find the repetitive units. Efficient and complete detection of repeats is provided together with interactive and detailed visualization of the spectral analysis of input sequence. We demonstrate the utility of our method with various examples that contain previously unannotated repeats. A Web server has been developed for convenient access to the automated program. AVAILABILITY: The Web server is available at http://www.imtech.res.in/raghava/srf and http://www2.imtech.res.in/raghava/srf

Algorithms↗

PRIME: automatically extracted PRotein Interactions and Molecular Information databasE.

With the exponentially increasing amount of information in the biomedical field, the significance of advanced information retrieval and information extraction, as well as the role of databases, has been increasing. PRIME is an integrated gene/protein informatics database based on natural language processing. It provides automatically extracted protein/family/gene/compound interaction information including both physical and genetic interactions, gene ontology based functions, and graphic pathway viewers. Gene/protein/family names and functional terms are recognized based on dictionaries developed in our laboratory. The interaction and functional information are extracted by syntactic dependencies and various phrase patterns. We have included about 920,000 (non-redundant) protein interactions and 360,000 annotated gene-function relationships for major eukaryotes. By combining the sequence and text information, the pathway comparison between two organisms and simple pathway deduction based on other organism interaction data, and pathway filtering using tissue expression data, are also available. This database is accessible at http://prime.ontology.ims.u-tokyo.ac.jp:8081.

Abstracting and Indexing↗