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Collateral missing value imputation: a new robust missing value estimation algorithm for microarray data.

MOTIVATION: Microarray data are used in a range of application areas in biology, although often it contains considerable numbers of missing values. These missing values can significantly affect subsequent statistical analysis and machine learning algorithms so there is a strong motivation to estimate these values as accurately as possible before using these algorithms. While many imputation algorithms have been proposed, more robust techniques need to be developed so that further analysis of biological data can be accurately undertaken. In this paper, an innovative missing value imputation algorithm called collateral missing value estimation (CMVE) is presented which uses multiple covariance-based imputation matrices for the final prediction of missing values. The matrices are computed and optimized using least square regression and linear programming methods. RESULTS: The new CMVE algorithm has been compared with existing estimation techniques including Bayesian principal component analysis imputation (BPCA), least square impute (LSImpute) and K-nearest neighbour (KNN). All these methods were rigorously tested to estimate missing values in three separate non-time series (ovarian cancer based) and one time series (yeast sporulation) dataset. Each method was quantitatively analyzed using the normalized root mean square (NRMS) error measure, covering a wide range of randomly introduced missing value probabilities from 0.01 to 0.2. Experiments were also undertaken on the yeast dataset, which comprised 1.7% actual missing values, to test the hypothesis that CMVE performed better not only for randomly occurring but also for a real distribution of missing values. The results confirmed that CMVE consistently demonstrated superior and robust estimation capability of missing values compared with other methods for both series types of data, for the same order of computational complexity. A concise theoretical framework has also been formulated to validate the improved performance of the CMVE algorithm. AVAILABILITY: The CMVE software is available upon request from the authors.

Algorithms↗

Modified SIMPSON O(n3) algorithm for the full sibship reconstruction problem.

MOTIVATION: The problem of reconstructing full sibling groups from DNA marker data remains a significant challenge for computational biology. A recently published heuristic algorithm based on Mendelian exclusion rules and the Simpson index was successfully applied to the full sibship reconstruction (FSR) problem. However, the so-called SIMPSON algorithm has an unknown complexity measure, questioning its applicability range. RESULTS: We present a modified version of the SIMPSON (MS) algorithm that behaves as O(n(3)) and achieves the same or better accuracy when compared with the original algorithm. Performance of the MS algorithm was tested on a variety of simulated diploid population samples to verify its complexity measure and the significant improvement in efficiency (e.g. 100 times faster than SIMPSON in some cases). It has been shown that, in theory, the SIMPSON algorithm runs in non-polynomial time, significantly limiting its usefulness. It has been also verified via simulation experiments that SIMPSON could run in O(n(a)), where a > 3. AVAILABILITY: Computer code written in Java is available upon request from the first author. CONTACT: Dmitry.Konovalov@jcu.edu.au.

Algorithms↗

An efficient randomized algorithm for contact-based NMR backbone resonance assignment.

MOTIVATION: Backbone resonance assignment is a critical bottleneck in studies of protein structure, dynamics and interactions by nuclear magnetic resonance (NMR) spectroscopy. A minimalist approach to assignment, which we call 'contact-based', seeks to dramatically reduce experimental time and expense by replacing the standard suite of through-bond experiments with the through-space (nuclear Overhauser enhancement spectroscopy, NOESY) experiment. In the contact-based approach, spectral data are represented in a graph with vertices for putative residues (of unknown relation to the primary sequence) and edges for hypothesized NOESY interactions, such that observed spectral peaks could be explained if the residues were 'close enough'. Due to experimental ambiguity, several incorrect edges can be hypothesized for each spectral peak. An assignment is derived by identifying consistent patterns of edges (e.g. for alpha-helices and beta-sheets) within a graph and by mapping the vertices to the primary sequence. The key algorithmic challenge is to be able to uncover these patterns even when they are obscured by significant noise. RESULTS: This paper develops, analyzes and applies a novel algorithm for the identification of polytopes representing consistent patterns of edges in a corrupted NOESY graph. Our randomized algorithm aggregates simplices into polytopes and fixes inconsistencies with simple local modifications, called rotations, that maintain most of the structure already uncovered. In characterizing the effects of experimental noise, we employ an NMR-specific random graph model in proving that our algorithm gives optimal performance in expected polynomial time, even when the input graph is significantly corrupted. We confirm this analysis in simulation studies with graphs corrupted by up to 500% noise. Finally, we demonstrate the practical application of the algorithm on several experimental beta-sheet datasets. Our approach is able to eliminate a large majority of noise edges and to uncover large consistent sets of interactions. AVAILABILITY: Our algorithm has been implemented in the platform-independent Python code. The software can be freely obtained for academic use by request from the authors.

Algorithms↗

Performance of a new single-chamber ICD algorithm: discrimination of supraventricular and ventricular tachycardia based on vector timing and correlation.

AIMS: Interval- and morphology-based algorithms have been used in modern implantable cardioverter defibrillators (ICDs) to discriminate supraventricular tachycardia (SVT) from other rhythms. A newly developed ICD discrimination algorithm, Rhythm ID (Guidant Corporation, St Paul, MN, USA), uses both interval-based metrics and an electrogram vector timing and correlation (VTC) algorithm in a dual-chamber ICD. In a single-chamber ICD, Rhythm ID contains only the VTC component. This study conducted a retrospective analysis of the performance of Rhythm ID for the detection of induced and spontaneous rhythms in a single-chamber ICD. METHODS AND RESULTS: This study gathered the data from a prospective, multicentre clinical trial. Ninety-six patients were implanted with a dual-chamber ICD. For this study, each episode was analysed to determine the performance of the single-chamber ICD Rhythm ID algorithm. The mean age of the patients implanted with the device was 67+/-11 years. Seventy-eight patients were male. The primary cardiovascular disease was coronary artery disease and the primary tachyarrhythmia was monomorphic ventricular tachycardia (VT). The mean follow-up time was 11.4 months. A total of 369 induced and spontaneous ventricular arrhythmias was analysed. The algorithm detected 100% of ventricular arrhythmias. Four hundred and forty-two SVT episodes were analysed, including 145 induced and 297 spontaneous. The SVTs were atrial fibrillation (n=199), atrial flutter (n=135), and 1:1 SVT (n=108). The single-chamber ICD Rhythm ID algorithm successfully discriminated 403 SVT episodes and achieved a specificity of 91%. CONCLUSION: The single-chamber version of Rhythm ID demonstrated high specificity without compromising sensitivity.

Aged↗

The use of a genetic algorithm for simultaneous mapping of multiple interacting quantitative trait loci.

Here we describe a general method for improving computational efficiency in simultaneous mapping of multiple interacting quantitative trait loci (QTL). The method uses a genetic algorithm to search for QTL in the genome instead of an exhaustive enumerative ("step-by-step") search. It can be used together with any method of QTL mapping based on a genomic search, since it only provides a more efficient way to search the genome for QTL. The computational demand decreases by a factor of approximately 130 when using genetic algorithm-based mapping instead of an exhaustive enumerative search for two QTL in a genome size of 2000 cM using a resolution of 1 cM. The advantage of using a genetic algorithm increases further for larger genomes, higher resolutions, and searches for more QTL. We show that a genetic algorithm-based search has efficiency higher than or equal to a search method conditioned on previously identified QTL for all epistatic models tested and that this efficiency is comparable to that of an exhaustive search for multiple QTL. The genetic algorithm is thus a powerful and computationally tractable alternative to the exhaustive enumerative search for simultaneous mapping of multiple interacting QTL. The use of genetic algorithms for simultaneous mapping of more than two QTL and for determining empirical significance thresholds using permutation tests is also discussed.

Algorithms↗

An automated data algorithm to distinguish screening and diagnostic colorectal cancer endoscopy exams.

Despite questions about accuracy, automated data are used increasingly for research and quality measurement. The goal of this study was to develop an automated data algorithm designed to distinguish screening and diagnostic endoscopy (sigmoidoscopy and colonoscopy) exams. We assessed the algorithm's ability to correctly classify the exams using paper medical records as the "gold standard." The algorithm used diagnostic codes to identify the indication of the endoscopies. The algorithm's ability to classify the indication varied by endoscopy exam. The sensitivities for identifying diagnostic sigmoidoscopy and colonoscopy were 48.1% and 23.8%, respectively. The algorithm missed most of the diagnostic endoscopies. Conversely, the sensitivities for identifying screening sigmoidoscopy and colonoscopy were high (87.9% and 84.4%, respectively) but were associated with low specificities. Our findings suggest that studies relying solely on automated data overestimate screening rates if indication is not considered. The automated algorithm presented here needs further improvements to better differentiate screening from diagnostic exams.

Aged↗

How to find a wombmate: validation of an algorithm to identify twin pairs in Linked Birth/Infant Death Files.

Linked Birth/Infant Death Files available from the National Center for Health Statistics identify an infant as a twin, but do not identify twin pairs. An algorithm based on maternal, paternal, and infant characteristics has been used to identify twin pairs, but the validity of this algorithm has never been tested. The Missouri linked birth/infant death file from 1980 to 1990 identifies twin pairs by a sequence number. The authors tested the rate and accuracy with which the algorithm identified true pairs in the Missouri file and whether estimates of risk and possible risk factors calculated from pairs of twins identified by the algorithm agreed with these characteristics as calculated from known twin pairs. The algorithm identified 96% (8,273 of 8,620) of true pairs and one false pair. Despite incomplete pair identification, and even identification of a false pair, estimates from the subset identified by the algorithm generally agreed well with characteristics measured from all twin pairs. Nonetheless, incorporation of a multiple birth sequence number into Linked Birth/Infant Death Files would enhance their utility.

Algorithms↗

Effective use of a novel rate-smoothing algorithm in atrial fibrillation by ventricular pacing.

BACKGROUND: It is still unknown whether a fast heart rate or an irregular ventricular response in atrial fibrillation causes tachycardiomyopathy. Reduction in the variability of RR intervals without an increase in heart rate might be an alternative treatment when antiarrhythmic drugs fail to control the irregularity accompanying atrial fibrillation. SUBJECTS AND METHODS: Eight patients underwent temporary right ventricular pacing, using a novel rate-smoothing algorithm prior to DC cardioversion or His bundle ablation. A rate-smoothing algorithm was utilized by right ventricular apical stimulation. Spontaneous and paced RR intervals during atrial fibrillation were quantified and processed for statistical analysis. RESULTS: The rate-smoothing algorithm resulted in a substantial reduction in the variance of the RR intervals (slow mode 73.1%, fast mode 40.0%) and RR range (slow mode 49.3%, fast mode 34.3%). In contrast to previous algorithms, the mean heart rate during pacing intervention in atrial fibrillation did not change significantly to the heart rate directly preceding the pacemaker intervention (+2%). CONCLUSIONS: This initial study of the novel rate-smoothing algorithm shows that pacing intervention is a relatively safe, rapid and reliable alternative therapy for controlling irregular ventricular rhythms due to atrial fibrillation. Incorporation of the algorithm in implantable pacemakers appears justified, but demands further prospective studies in patients to evaluate relief of symptoms and reduction of tachycardiomyopathy due to atrial fibrillation.

Aged↗

Comparison of TLD algorithms for monochromatic fluorescent radiation and continuous spectrum X rays.

A personal dosimetry system is required to measure the personal dose equivalent accurately in a wide range of radiation fields. However, the dose evaluation algorithm at the Korea Atomic Energy Research Institute (KAERI) has been developed with the spectral X ray fields described in the American National Standards Institute (ANSI) Standard N13.11 and the actual fields to be monitored may be significantly different from these. To evaluate the dose more accurately when workers are exposed to non-ANSI N13.11 radiation fields, a dose evaluation algorithm using monochromatic radiation (monochromatic algorithm) was developed using the experimental data of the energy responses of CaSO4:Dy thermoluminescent materials irradiated by monochromatic fluorescent X ray fields recently established at KAERI; this was compared with another algorithm developed on the basis of the ANSI N13.11 continuous spectrum X ray fields (spectrum algorithm). The paper concludes with discussions about some results of the algorithm test, including mixed field irradiation and angular response, conducted in an International Atomic Energy Authority/Regional Cooperation of Asia (IAEA/RCA) intercomparison study.

Algorithms↗

Diagnosing left ventricular dysfunction after myocardial infarction: the Dundee algorithm.

Large-scale trials of angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) suggest that the benefits are greatest in patients with left ventricular (LV) dysfunction. However, early evaluation of LV function in all patients after AMI by current methods can be difficult due to a lack of resources and skilled personnel. Thus a clinical algorithm that could be used at the bedside to reliably identify patients with a left ventricular ejection fraction (LVEF) < or = 40% would be helpful as an occasional alternative to echocardiography. We have devised such an algorithm based on the presence of one of: (i) clinical signs of heart failure; (ii) an index Q-wave anterior myocardial infarction; (iii) lack of thrombolytic therapy when there is a history of two or more previous myocardial infarctions and a CK rise > 1000 U/l. We tested this new algorithm prospectively in the coronary care units of two hospitals (one UK and one USA). In the UK centre, the sensitivity and specificity of the algorithm at identifying patients with a LVEF < or = 40% were 82% and 72%, respectively. In the US centre, the sensitivity of the algorithm was 91% and the specificity 78% at identifying patients with LV dysfunction. We have validated a simple clinical algorithm which can be used at the bedside for identifying patients who would benefit from an ACE inhibitor after AMI.

Aged↗

Development of an algorithm for TLD badge system for dosimetry in the field of X and gamma radiation in terms of Hp(10).

In view of the introduction of International Commission on Radiation Units and Measurements operational quantities Hp(10) and Hp(0.07), defined for individual monitoring, it became necessary to develop an algorithm that gives direct response of the dosemeter in terms of the operational quantities. Hence, for this purpose and also to improve the accuracy in dose estimation especially in the mixed fields of X ray and gamma, an algorithm was developed based on higher-order polynomial fit of the data points generated from the dose-response of discs under different filter regions of the present TL dosemeter system for known delivered doses. Study on the response of the BARC TL dosemeter system based on CaSO(4):Dy Teflon thermoluminescence dosemeter discs in the mixed fields of X and gamma radiation was carried out to ensure that the accuracies are within the prescribed limits recommended by the international organisations. The prevalent algorithm, based on the ratios of the disc response under various filters regions of the dosemeter to pure photons, was tested for different proportion of two radiations in case of mixed field dosimetry. It was found that the accuracy for few fields is beyond the acceptable limit in case of prevalent algorithm. The new proposed algorithm was also tested in mixed fields of photon fields and to pure photon fields of varied angles. It was found that the response of the dosemeter in mixed fields of photons and its angular response are satisfactory. The new algorithm can be used to record and report the personal dose in terms of Hp(10) as per the international recommendation for the present TL dosemeter.

Algorithms↗

A digital filterbank hearing aid: three digital signal processing algorithms--user preference and performance.

OBJECTIVE: Three digital signal processing algorithms named RangeEar, DynEar, and LinEar were compared with regard to user preference and performance when a wearable digital filterbank hearing aid was used. All three algorithms provided individual frequency shaping via a seven-band filterbank. Compression was used in a low-frequency (LF) and a high-frequency (HF) channel. RangeEar and DynEar used wide dynamic range syllabic compression in the LF channel, whereas LinEar used compression limiting. In the HF channel, RangeEar used a slow acting automatic volume control, whereas DynEar and LinEar used compression limiting. The subjects had access to a manual volume control when using the LinEar or DynEar options. DESIGN: The study included 13 hearing aid users with symmetrical sensorineural losses. In a 1 mo long blind field test, the RangeEar algorithm was compared with the preferred algorithm from an earlier study, DynEar or LinEar. A data logger function was included for objective recording of the total time each algorithm was used and how the volume controls were used. The preference was based on the time used for each algorithm and from subjective statements. Threshold signal-to-noise ratio (S/N-threshold) for speech was tested, and sound quality ratings were obtained through a questionnaire. RESULTS: Of the 13 subjects, six preferred the RangeEar fitting and another four preferred the DynEar fitting. Two subjects preferred the LinEar fitting and one had equal preference for RangeEar and LinEar. The results from the questionnaire showed that the preferred fittings were rated higher concerning overall impression of sound quality and clearness, whereas the S/N for the speech test did not show any differences. Preferences, where stated, could be predicted from auditory dynamic range measurements in the LF and HF frequency ranges. The mean dynamic range was broader for low and narrower for high frequencies for those who preferred the RangeEar or DynEar fitting as compared with those who preferred the LinEar fitting. The preference between RangeEar and DynEar was predicted by differences in the HF range, with the narrower dynamic range for the DynEar preference subjects. CONCLUSION: Most subjects preferred the option of having a wide dynamic range syllabic compressor in the LF channel and having the overall gain in the HF channel adjustable, either manually (DynEar) or automatically (RangeEar).

Adult↗

Usability of semiautomatic segmentation algorithms for tumor volume determination.

RATIONALE AND OBJECTIVES: Tumor volume is an important parameter for clinical decision making. At present, semiautomatic image segmentation is not a standard for tumor volumetry. The aim of this work was to investigate the usability of semiautomatic algorithms for tumor volume determination. METHODS: Semiautomatic region- and volume-growing, isocontour, snakes, hierarchical, and histogram-based segmentation algorithms were tested for accuracy, contour variability, and time performance. The test were performed on a newly developed organic phantom for the simulation of a human liver and liver metastases. The real tumor volumes were measured by water displacement. These measured volumes were used as the gold standard for determining the accuracy of the algorithms. RESULTS: Variability of the segmented volumes ranging from 3.9 +/- 3.2% (isocontour algorithm) to 11.5 +/- 13.9% (hierarchical segmentation) was observed. The segmentation time per slice varied between 32 (volume-growing) and 72 seconds (snakes) on an IBM/RS6000 workstation. CONCLUSIONS: Only the region-growing and isocontour algorithms have the potential to be used for tumor volumetry. However, further improvements of these algorithms are necessary before they can be placed into clinical use.

Algorithms↗

The Texas Children's Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder.

OBJECTIVES: To develop consensus guidelines for medication treatment algorithms for childhood major depressive disorder (MDD) based on scientific evidence and clinical opinion when science is lacking. The ultimate goal of this approach is to synthesize research and clinical experience for the practitioner and to increase the uniformity of preferred treatment for childhood MDD. A final goal is to develop an approach that can be tested as to whether it improves clinical outcomes for children and adolescents with MDD. METHOD: A consensus conference was held. Participants included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review and use clinical evidence to recommend specific pharmacological approaches for treatment of MDD in children and adolescents. After a series of presentations of current research evidence and panel discussion, the consensus panel met, agreed on assumptions, and drafted the algorithms. The process initially addressed strategies of treatment and then tactics to implement the strategies. RESULTS: Consensually agreed-upon algorithms for major depressions (with and without psychosis) and comorbid attention deficit disorders were developed. Treatment strategies emphasized the use of selective serotonin reuptake inhibitors. The algorithm consists of systematic strategies for treatment interventions and recommended tactics for implementation of the strategies, including medication augmentation and medication combinations. Participants recommended prospective evaluation of the algorithms in various public sector settings, and many volunteered as sites for such an evaluation. CONCLUSIONS: Using scientific and clinical experience, consensus-derived algorithms for children and adolescents with MDD can be developed.

Adolescent↗

CT reconstruction algorithm selection in the evaluation of solitary pulmonary nodules.

OBJECTIVE: We have observed a significant CT artifact in the evaluation of lung nodules that occurred with the use of high-spatial-frequency reconstruction algorithms. We have seen this lead to a false-positive diagnosis of calcification in a small uncalcified lung nodule. Because of the seriousness of misinterpretation of benign calcification in an uncalcified nodule, we reviewed the various effects of several reconstruction algorithms on different scanners. MATERIALS AND METHODS: Using high-spatial-frequency, smoothing, and intermediate reconstruction algorithms, we studied standardized cylinders in a CT reference phantom and lung nodules in eight patients. Algorithms on four CT scanners were analyzed. RESULTS: We found peripheral edge enhancement artifact on some CT images of phantom cylinders and uncalcified lung nodules. The images with edge enhancement artifact were obtained from two scanners with the use of high-spatial-frequency algorithms (Picker 1200 SX and GE HiSpeed Advantage). CONCLUSION: Use of high-spatial-frequency reconstruction algorithms for the analysis of lung nodules with thin-section CT may lead to an erroneous diagnosis of calcification.

Algorithms↗

Comparison of professional judgment versus an algorithm for nutrition status classification.

OBJECTIVES: The classification of a patient's nutrition status is important for identifying patients who require nutrition care, for designing effective nutrition interventions, and for measuring severity of illness. The objective of this study was to evaluate the reliability and validity of two variants of the Department of Veterans Affairs' nutrition status classification: professional judgment versus an algorithm. METHODS: The study consisted of two phases, both of which included providing a sample of approximately 60 registered dietitians and 60 clinical dietetic technicians with data on 16 (phase I) and 20 (phase II) patients, to which they assigned nutrition statuses using both professional judgment and the algorithm. Improvements in instructions and training were implemented between the two phases. Interrater reliability of the responses was calculated, and content validity was measured by comparing the staff's responses with those of an expert panel. RESULTS: Reliability improved significantly between phases for both professional judgment and the algorithm. Greater reliability and validity were observed with use of the algorithm, by both dietitians and technicians, during both phases. CONCLUSION: Classification of a patient's nutrition status is important in the delivery of cost-effective health care. The Department of Veterans Affairs' nutrition status classification is a good one for assessing nutrition status quickly and reliably, especially when an algorithm is used. The results underscore the advantages of a classification system based on an algorithm when the system is designed to be used by many different staff across multiple facilities.

Adult↗

Simplified algorithms for the estimation of 99Tcm-MAG3 clearance.

The aim of this study was to evaluate two formulae allowing the determination of MAG3 clearance by means of a single blood sample, namely Bubeck's formula and Russell's formula. As a first step, a simulation study was performed with the two single-sample algorithms to predict MAG3 clearance as a function of plasma concentration, using various times for blood sampling and various body surface areas. As a second step, a validation study on 47 adult patients with varying renal function allowed a clinical comparison between the reference technique, namely the multiple blood sample technique, and the two simplified techniques. The simplified algorithms were calculated using the fitted value at 44 min. In the simulation study, whatever the time of blood sampling or the level of correction introduced for body surface area, the results obtained by means of Bubeck's algorithm diverged significantly from those of Russell's algorithm, for low clearance values as well as for high clearance values. The curve of the differences between the two methods had a typical boomerang shape. In the clinical study, the difference between Russell's algorithm and the reference method was generally within 20 ml.min-1, with no systematic bias; with Bubeck's algorithm there was a marked underestimation, both in the low and high clearance ranges. We suggest Russell's single-sample method is the method of choice.

Adult↗

Risk-based versus alternative algorithms for antibiotic prophylaxis among women seeking early suction abortion: a cost-effectiveness simulation.

BACKGROUND: Particularly in resource-poor settings, simple, inexpensive, and cost-effective algorithms are needed to direct antibiotic prophylaxis to prevent sequelae of infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and bacterial vaginosis-associated organisms among women undergoing abortion. GOAL: To assess the prevalence of and risk factors for infections among women seeking abortion in Bali, Indonesia, and to use these data in designing a cost-effective risk-based prophylaxis algorithm. STUDY DESIGN: A cross-sectional analysis and data-based simulation of risk-based and alternative prophylaxis algorithms were performed. RESULTS: The risk-based algorithm would have provided prophylaxis to 70% (95% CI, 53-83%) of women with cervical infection, 64% (95% CI, 54-74%) of those with bacterial vaginosis, and 57% (95% CI, 42-72%) of those with trichomoniasis. For cervical infection, the algorithm was more cost effective than all others evaluated. The cost-effectiveness was acceptable for bacterial vaginosis. CONCLUSIONS: Risk-based algorithms may be cost effective in identifying women likely to benefit from preabortion prophylaxis. Prospective evaluation is needed to validate these findings.

Abortion, Induced↗