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Biological applications of support vector machines.

One of the major tasks in bioinformatics is the classification and prediction of biological data. With the rapid increase in size of the biological databanks, it is essential to use computer programs to automate the classification process. At present, the computer programs that give the best prediction performance are support vector machines (SVMs). This is because SVMs are designed to maximise the margin to separate two classes so that the trained model generalises well on unseen data. Most other computer programs implement a classifier through the minimisation of error occurred in training, which leads to poorer generalisation. Because of this, SVMs have been widely applied to many areas of bioinformatics including protein function prediction, protease functional site recognition, transcription initiation site prediction and gene expression data classification. This paper will discuss the principles of SVMs and the applications of SVMs to the analysis of biological data, mainly protein and DNA sequences.

Algorithms↗

Automatic intrinsic DNA curvature computation from AFM images.

Critical information on several biological processes such as DNA-protein interactions and DNA transcription can be derived from analysis of DNA curvature. Under thermal perturbation, the curvature is composed of static and dynamic contributions, thus, can be described as the sum of intrinsic curvature and a fluctuation contribution. Without considering thermal agitations, the DNA curvature is reducible to the intrinsic component, which is a function of the DNA nucleotide sequence only. In this paper, we present an automated algorithm to determine the DNA intrinsic curvature profiles and the molecular spatial orientations in Atomic Force Microscope images. The algorithm allows to reconstruct the intrinsic curvature profile by filtering the thermal contribution. It detects fragment orientation on atomic force microscope images without labels with a percentage of correct molecular-orientation detection of 96.79% in computer-generated benchmarks, for molecules with a high curvature peak. The automated algorithm reconstructs the intrinsic curvature profile of DNA molecules with a mean square error of 3.8122 x 10(-4) rads over a profile with a central peak value of 0.196 rads, and 6.1 x 10(-3) rads over a curvature profile with two symmetric peaks of about 0.08 rads. Moreover, it correctly detects the location of the peaks in the molecules with a deviation of about 1% of molecule length.

Algorithms↗

Quantitative comparison of mitotic spindles by confocal image analysis.

The mitotic spindle is a subcellular protein structure that facilitates chromosome segregation and is crucial to cell division. We describe an image processing approach to quantitatively characterize and compare mitotic spindles that have been imaged three dimensionally using confocal microscopy with fixed-cell preparations. The proposed approach is based on a set of features that are computed from each image stack representing a spindle. We compare several spindle datasets of varying biological (genotype) and/or environmental (drug treatment) conditions. The goal of this effort is to aid biologists in detecting differences between spindles that may not be apparent under subjective visual inspection, and furthermore, to eventually automate such analysis in high-throughput scenarios (thousands of images) where manual inspection would be unreasonable. Experimental results on positive- and negative-control data indicate that the proposed approach is indeed effective. Differences are detected when it is known they do exist (positive control) and no differences are detected when there are none (negative control). In two other experimental comparisons, results indicate structural spindle differences that biologists had not observed previously.

Algorithms↗

DNAfan: a software tool for automated extraction and analysis of user-defined sequence regions.

SUMMARY: DNAfan (DNA Feature ANalyzer) is a tool combining sequence-filtering and pattern searching. DNAfan automatically extracts user-defined sets of sequence fragments from large sequence sets. Fragments are defined by annotated gene feature keys and co- or non-occurring patterns within the feature or close to it. A gene feature parser and a pattern-based filter tool localizes and extracts the specific subset of sequences. The selected sequence data can subsequently be retrieved for analyses or further processed with DNAfan to find the occurrence of specific patterns or structural motifs. DNAfan is a powerful tool for pattern analysis. Its filter features restricts the pattern search to a well-defined set of sequences, allowing drastic reduction in false positive hits. AVAILABILITY: http://bighost.ba.itb.cnr.it:8080/Framework.

Algorithms↗

An approach to automated particle picking from electron micrographs based on reduced representation templates.

Reduced representation templates are used in a real-space pattern matching framework to facilitate automatic particle picking from electron micrographs. The procedure consists of five parts. First, reduced templates are constructed either from models or directly from the data. Second, a real-space pattern matching algorithm is applied using the reduced representations as templates. Third, peaks are selected from the resulting score map using peak-shape characteristics. Fourth, the surviving peaks are tested for distance constraints. Fifth, a correlation-based outlier screening is applied. Test applications to a data set of keyhole limpet hemocyanin particles indicate that the method is robust and reliable.

Algorithms↗

Capturing expert knowledge with argumentation: a case study in bioinformatics.

MOTIVATION: The output of a bioinformatic tool such as BLAST must usually be interpreted by an expert before reliable conclusions can be drawn. This may be based upon the expert's experience, additional data and statistical analysis. Often the process is laborious, goes unrecorded and may be biased. Argumentation is an established technique for reasoning about situations where absolute truth or precise probability is impossible to determine. RESULTS: We demonstrate the application of argumentation to 3D-PSSM, a protein structure prediction tool. The expert's interpretation of results is represented as an argumentation framework. Given a 3D-PSSM result, an automated procedure constructs arguments for and against the conclusion that the result is a good predictor of protein structure. In addition to capturing the unique expertise of the author of 3D-PSSM for distribution to users, an improvement in recall of 5-10 percentage points is achieved. This technique can be applied to a wide range of bioinformatic tools. AVAILABILITY: Example public server and benchmarking data are available at http://www.sbg.bio.ic.ac.uk/~brj03/argumentation/paper/. Source code available on request.

Amino Acid Sequence↗

Classification of brain tumours using short echo time 1H MR spectra.

The purpose was to objectively compare the application of several techniques and the use of several input features for brain tumour classification using Magnetic Resonance Spectroscopy (MRS). Short echo time 1H MRS signals from patients with glioblastomas (n = 87), meningiomas (n = 57), metastases (n = 39), and astrocytomas grade II (n = 22) were provided by six centres in the European Union funded INTERPRET project. Linear discriminant analysis, least squares support vector machines (LS-SVM) with a linear kernel and LS-SVM with radial basis function kernel were applied and evaluated over 100 stratified random splittings of the dataset into training and test sets. The area under the receiver operating characteristic curve (AUC) was used to measure the performance of binary classifiers, while the percentage of correct classifications was used to evaluate the multiclass classifiers. The influence of several factors on the classification performance has been tested: L2- vs. water normalization, magnitude vs. real spectra and baseline correction. The effect of input feature reduction was also investigated by using only the selected frequency regions containing the most discriminatory information, and peak integrated values. Using L2-normalized complete spectra the automated binary classifiers reached a mean test AUC of more than 0.95, except for glioblastomas vs. metastases. Similar results were obtained for all classification techniques and input features except for water normalized spectra, where classification performance was lower. This indicates that data acquisition and processing can be simplified for classification purposes, excluding the need for separate water signal acquisition, baseline correction or phasing.

Brain Chemistry↗

The Athena semi-automated karyotyping system.

In this article we describe Athena, a system that provides for semi-automated karyotyping of metaphase spreads. The system is based upon the Macintosh II computer. It uses software that is written entirely in C and consists of approximately 200 Kbytes of executable code. Athena provides automated segmentation of metaphase images into individual chromosomes, automated measurements on each banded chromosome, and automated classification into the standard Paris-convention karyotype. Furthermore, the system provides the ability to construct one or more chromosome data bases to represent the types of metaphase spreads and staining techniques that may be used in a given laboratory. Because we believe that it is impossible to construct a system that can achieve perfect segmentation, perfect separation of touching and overlapping chromosomes, perfect localization of the centromeres, and perfect classification, the system offers the possibility for interaction at each of the above stages using the well-accepted Macintosh user interface.

Centromere↗

Accessing heart dynamics to estimate durations of heart sounds.

Segmentation of the phonocardiogram into its major sound components is the first step in the automated diagnosis of cardiac abnormalities. Almost all of the existing phonocardiogram segmentation algorithms utilize absolute amplitude or frequency characteristics of heart sounds, which vary from one cardiac cycle to the other and across different patients. The objective of this work is to provide an efficient phonocardiogram segmentation technique, under difficult recording situations, by utilizing the underlying complexity of the dynamical system (heart) giving rise to the heart sound. Complexity-based segmentation is invariant to amplitude and frequency variations of the heart sound and yields better time gates for heart sounds.

Algorithms↗

CT hepatic venography: 3D vascular segmentation for preoperative evaluation.

Preventing complications during hepatic surgery in living-donor transplantation or in oncologic resections requires a careful preoperative analysis of the hepatic venous anatomy. Such an analysis relies on CT hepatic venography data, which enhances the vascular structure due to contrast medium injection. However, a 3D investigation of the enhanced vascular anatomy based on typical computer vision tools is ineffective because of the large amount of occlusive opacities to be removed. This paper proposes an automated 3D approach for the segmentation of the vascular structure in CT hepatic venography, providing the appropriate tools for such an investigation. The developed methodology relies on advanced topological and morphological operators applied in mono- and multiresolution filtering schemes. It allows to discriminate the opacified vessels from the bone structures and liver parenchyma regardless of noise presence or inter-patient variability in contrast medium dispersion. The proposed approach was demonstrated at different phases of hepatic perfusion and is currently under extensive validation in clinical routine.

Algorithms↗

Automated nomenclature of bronchial branches extracted from CT images and its application to biopsy path planning in virtual bronchoscopy.

We propose a novel anatomical labeling algorithm for bronchial branches extracted from CT images. This method utilizes multiple branching models for anatomical labeling. In the actual labeling process, the method selects the best candidate models at each branching point. Also a special labeling procedure is proposed for the right upper lobe. As an application of the automated nomenclature of bronchial branches, we utilized anatomical labeling results for assisting biopsy planning. When a user inputs a target point around suspicious regions on the display of a virtual bronchoscopy (VB) system, the path to the desired position is displayed as a sequence of anatomical names of branches. We applied the proposed method to 25 cases of CT images. The labeling accuracy was about 90%. Also the paths to desired positions were generated by using anatomical names in VB.

Algorithms↗

Toward automatic phenotyping of developing embryos from videos.

We describe a trainable system for analyzing videos of developing C. elegans embryos. The system automatically detects, segments, and locates cells and nuclei in microscopic images. The system was designed as the central component of a fully automated phenotyping system. The system contains three modules 1) a convolutional network trained to classify each pixel into five categories: cell wall, cytoplasm, nucleus membrane, nucleus, outside medium; 2) an energy-based model, which cleans up the output of the convolutional network by learning local consistency constraints that must be satisfied by label images; 3) a set of elastic models of the embryo at various stages of development that are matched to the label images.

Algorithms↗

Automated recognition of lateral from PA chest radiographs: saving seconds in a PACS environment.

Images acquired in a two-view digital chest examination are frequently not electronically distinguishable. As a result the lateral and posterioanterio (PA) images are often improperly positioned on a PACS work station. A series of 1998 chest radiographs (999 lateral, 999 PA or AP) were used to develop a neural network classifier. The images were down-sampled to 16 x 16 matrices, and a feed-forward neural network was trained and tested using the "leave-one-out" method. Using five nodes in the hidden layer, the neural network correctly identified 987 of the 999 test cases (98.8%) (average of six runs). The simple architecture and speed of this technique suggests that it would be a useful addition to PACS work station software. The accumulated time saved by correctly positioning the lateral and PA chest images on the work station monitors in accordance with each radiologist's hanging protocols was estimated to be about 1 week of radiologist time per year.

Electronic Data Processing↗

Facial action recognition for facial expression analysis from static face images.

Automatic recognition of facial gestures (i.e., facial muscle activity) is rapidly becoming an area of intense interest in the research field of machine vision. In this paper, we present an automated system that we developed to recognize facial gestures in static, frontal- and/or profile-view color face images. A multidetector approach to facial feature localization is utilized to spatially sample the profile contour and the contours of the facial components such as the eyes and the mouth. From the extracted contours of the facial features, we extract ten profile-contour fiducial points and 19 fiducial points of the contours of the facial components. Based on these, 32 individual facial muscle actions (AUs) occurring alone or in combination are recognized using rule-based reasoning. With each scored AU, the utilized algorithm associates a factor denoting the certainty with which the pertinent AU has been scored. A recognition rate of 86% is achieved.

Algorithms↗

GP3: GenePix post-processing program for automated analysis of raw microarray data.

UNLABELLED: Here we describe an automated and customizable program to correct, filter and normalize raw microarray data captured using GenePix, a commonly used microarray image analysis application. Files can be processed individually or in batch mode for increased throughput. User defined inputs specify the stringency of data filtering and the method and conditions of normalization. The output includes gene summaries for replicate spots and descriptive statistics for each experiment. The source code (Perl) can also be adapted to handle raw data output from other image analysis applications. AVAILABILITY: http://bch.msu.edu/~zacharet/microarray/GP3.html

Algorithms↗

New automated iris image acquisition method.

I propose a new iris image acquisition method based on wide- and narrow-view iris cameras. The narrow-view camera has the functionalities of automatic zooming, focusing, panning, and tilting based on the two-dimensional and three-dimensional eye positions detected from the wide- and narrow-view stereo cameras. By using the wide- and narrow-view iris cameras, I compute the user's gaze position, which is used for aligning the X-Y position of the user's eye, and I use the visible-light illuminator for fake-eye detection.

Algorithms↗

Efficient center-line extraction for quantification of vessels in confocal microscopy images.

In this paper we present a novel method for the three-dimensional (3-D) centerline extraction of elongated objects such as vessels. This method combines the basic ideas in distance transform-based, thinning, and path planning methods to extract thin and connected centerlines. This efficient approach needs no user interaction or any prior knowledge of the object shape. We used the path planning approach, which has exclusively been used in the virtual endoscopy or robotics, to obtain the medial curve of the objects. To make our approach fully automated, a distance transform mapping is used to identify the end points of the object branches. The initial paths are also constructed on the surface of the object, traversing the same distance map. Then a thinning algorithm centralizes the paths. The proposed approach is especially efficient for centerline extraction of the complex branching structures. The method has been applied on the confocal microscopy images of rat brains and the results confirm its efficiency in extracting the medial curve of vessels, essential for the computation of quantitative parameters.

Algorithms↗

Isotopic pattern and accurate mass determination in urine drug screening by liquid chromatography/time-of-flight mass spectrometry.

An efficient method was developed for toxicological drug screening in urine by liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry. The method relies on a large target database of exact monoisotopic masses representing the elemental formulae of reference drugs and their metabolites. Mass spectral identification is based on matching measured accurate mass and isotopic pattern (SigmaFit) of a sample component with those in the database. Data post-processing software was developed for automated reporting of findings in an easily interpretable form. The mean and median of SigmaFit for true-positive findings were 0.0066 and 0.0051, respectively. The mean and median of mass error absolute values for true-positive findings were 2.51 and 2.17 ppm, respectively, corresponding to 0.65 and 0.60 mTh. For routine screening practice, a SigmaFit tolerance of 0.03 and a mass tolerance of 10 ppm were chosen. Ion abundance differences from urine extracts did not affect the accuracy of the automatically acquired SigmaFit or mass values. The results show that isotopic pattern matching by SigmaFit is a powerful means of identification in addition to accurate mass measurement.

Algorithms↗