A systematic comparison and evaluation of biclustering methods for gene expression data

MOTIVATION: In recent years, there have been various efforts to overcome the limitations of standard clustering approaches for the analysis of gene expression data by grouping genes and samples simultaneously. The underlying concept, which is often referred to as biclustering, allows to identify sets of genes sharing compatible expression patterns across subsets of samples, and its usefulness has been demonstrated for different organisms and datasets. Several biclustering methods have been proposed in the literature; however, it is not clear how the different techniques compare with each other with respect to the biological relevance of the clusters as well as with other characteristics such as robustness and sensitivity to noise. Accordingly, no guidelines concerning the choice of the biclustering method are currently available. RESULTS: First, this paper provides a methodology for comparing and validating biclustering methods that includes a simple binary reference model. Although this model captures the essential features of most biclustering approaches, it is still simple enough to exactly determine all optimal groupings; to this end, we propose a fast divide-and-conquer algorithm (Bimax). Second, we evaluate the performance of five salient biclustering algorithms together with the reference model and a hierarchical clustering method on various synthetic and real datasets for Saccharomyces cerevisiae and Arabidopsis thaliana. The comparison reveals that (1) biclustering in general has advantages over a conventional hierarchical clustering approach, (2) there are considerable performance differences between the tested methods and (3) already the simple reference model delivers relevant patterns within all considered settings.     

A comparison of different methods used for the quantitative evaluation of biomass of freshwater phytoplankton

Although in a strict sense the term phytoplankton biomass only refers to living algal material, in aquatic ecology the term has been associated with a variety of biological and biochemical procedures used to quantify the particulate matter suspended in natural waters. Relative merits of different biomass characteristics have been studied in three Dutch freshwater lakes with great differences in absolute biomass. Parallel determinations have been made of seston dry weight and supplementary elementary and caloric analyses of seston, of chlorophyll-a concentration and supplementary paper chromatographic analyses of pigment extracts, of particle concentration and particle size distribution as studied with an electronic particle counter, and of phytoplankton cell volume as calculated from the results of microscopic enumeration and sizing of algae. In this way an attempt was made to create a detailed picture of the nature of the seston of the three freshwater lakes.Different analytical techniques give strikingly different information, the accuracy of any method is largely dependent on the circumstances present, and different biomass characteristics therefore are only of value in limited spheres. It is suggested to distinguish between total seston characteristics (e.g. seston dry weight, particulate organic carbon, total particle volume) and strictly algological biomass characteristics (e.g. chlorophyll-a concentration, phytoplankton cell volume). The pattern of growth of phytoplankton populations shown by e.g. chlorophyll-a concentration may differ markedly from that indicated by e.g. total particle volume or seston dry weight. Also, to more or less extent the wax and wane of phytoplankton populations may go undetected among the total seston. Apparently, there is no one method of estimating biomass and no conversion factor that may serve for general purposes. In general, unambiguous information on the nature of the seston of natural waters may only be obtained by estimating total seston characteristics and algological biomass characteristics simultaneously. Depending on the objective of the investigation supplementary component analyses should be carried out to guarantee the correct interpretation of the results.     

A quantitative comparison of data evaluation methods to derive diagnostic reference levels for CT from a dosimetric survey: Correlation analysis compared to simple evaluation strategies

ObjectivesTo compare simple and sophisticated evaluation strategies for CT dosimetry surveys with focus on DRLs.MethodsBased on data from a nationwide Austrian CT dose survey, different evaluation strategies are compared. These were pooled data analysis, weight banding excluding data from patients with weights outside ±20 kg of the standard weights (70 and 75.6 kg representing the actual average weight), and a regression method estimating DLP probability distributions for the standard patient for each scanner before calculating quartiles.ResultsIn the abdomen and chest region, weight restriction (?9% and ?4% around 70 and 75.6 kg, respectively, compared to pooled data analysis) and statistically weighting each scanner equally (?9%) have the largest effect on DRLs derived. However, the difference in 3rd quartiles calculated using weight restriction alone compared to regression analysis is relatively small (<1% for 70 ± 20 and ?6% for 75.6 ± 20 kg, respectively, trunk region). In the head/neck region the effect of weight restriction is less than in for scans of the trunk (?1.3% and ?0.2%, respectively); the most prominent changes resulted from excluding scanners with less than 10 patient cases (?5%), and equally weighting scanners rather than cases (?3%).ConclusionFor adult CT examinations (different to a paediatric survey), quite simple evaluation strategies yield results very comparable to those from sophisticated strategies.     

Toxoplasmosis in pregnancy: evaluation of diagnostic methods

Toxoplasmosis in pregnancy is usually subclinic or associated with non specific symptoms. Diagnosis and timing of infection are usually based on serological tests. In this short review we tried to summarize the serological patterns we can encounter and to discuss the interpretation of test results.     

In vivo magnetic resonance spectroscopy in the evaluation of mitochondrial disorders

Magnetic resonance spectroscopy (MRS) has been utilized to study several metabolic pathways in vivo and in live tissues in vitro non-invasively. Despite its inherited lack of sensitivity, its application has extended all the way to in situ human tissues and organs since proper technical advancements were devised. Examples of its application described here demonstrate the value of in vivo MRS as a technique that determines parameters of mitochondrial dysfunction directly and indirectly which could be of value for the diagnosis, prognosis, and follow-up of mitochondrial disorders.     

A comparison of methods for estimating the lactate threshold

The purpose of this study was to examine the accuracy of tests that may be used by distance runners to estimate the lactate threshold. Competitive distance runners/triathletes (N = 27) performed a criterion test that directly measured (blood lactate of 4.0 mmol.L(-1)) the lactate threshold. Subjects then performed 4 tests (VDOT, 3,200-m time trial, 30-minute time trial, Conconi) that estimate the threshold. Mean estimations of the running velocity at the lactate threshold from the 30-minute time trial (standard error of the estimate, SEE, 0.21 m.s(-1)) and VDOT (SEE 0.41 m.s(-1)) methods did not differ (P>0.05) from the criterion. In terms of heart rate, the 30-minute time trial estimation did not significantly differ (SEE 8.0 b.min(-1)) from criterion. These findings suggest that the 30-minute time-trial method should be considered by coaches and distance runners/triathletes as a method for estimating both the running velocity and heart rate at the lactate threshold.     

Strategies for treating disorders of the mitochondrial genome

Defects of the mitochondrial genome are a significant cause of disease. Patients suffer from a wide variety of clinical presentations, ranging from fatal infantile disease to mild muscle weakness. Most disorders, however, are characterized by inexorable progression. As mutations often cause defects in several components of the complexes that couple oxidative phosphorylation, this terminal state of oxidative metabolism cannot be readily bypassed by dietary means, leading to the search for novel therapies. In this article, we present the theory behind several concepts and report progress. We also discuss some of the recent difficulties encountered in the progress towards an antigenomc approach to treating mtDNA disorders.     

A comparison of three flow cytometry methods for evaluating mitochondrial damage during staurosporine-induced apoptosis in Jurkat cells.

Measuring cytochrome c release during apoptosis provides valuable information about the nature and extent of apoptosis. Several years ago a flow cytometric method (based on selective permeabilization of the plasma membrane with digitonin) was developed that has advantages over other techniques. These experiments describe a comprehensive evaluation of that method. Apoptosis was triggered in Jurkat cells with staurosporine and then flow cytometry was used to measure three aspects of mitochondrial damage: (1) cytochrome c release (with the digitonin assay and a commercially available kit based on the same principle), using a DNA-binding dye to define cell cycle stage; (2) loss of mitochondrial cardiolipin, assessed by a decrease in 10 N-nonyl acridine orange (NAO) binding; and (3) loss of mitochondrial membrane potential, assessed by a decrease in tetramethylrhodamineethylester (TMRE) binding. The results from these three assays were compared with an antibody-based assay for cleaved caspase 3. The digitonin assay and the commercially available kit gave comparable results, showing that staurosporine caused cytochrome c release in all phases of the cell cycle and clearly defining those cells that had lost DNA due to internucleosomal DNA fragmentation. The pattern of fluorescence demonstrated that the mitochondrial apoptotic pathway was either the sole or the predominant pathway to be activated and that cytochrome c release in an individual cell was all-or-nothing. However, comparison with the other assays showed that the cytochrome c release assay underestimated the true extent of apoptosis. This was caused by the selective loss of some digitonin-treated apoptotic cells. The flow cytometry assay for cytochrome c release provides valuable information but it underestimates the percentage of apoptotic cells.     

两种获取鱼类线粒体DNA的方法比较

直接从鱼类组织提取线粒体DNA和先提取基因组DNA再用相应引物PCR扩增所需mtDNA某一区域序列片段是获取鱼类mtDNA切实可行的两种方法。对这两种方法在使用过程中的注意事项、各自的优缺点及应用范围进行了较为细致的比较,为更好地利用mtDNA这一重要分子标记研究鱼类mtDNA的遗传多态提供参考。     

A comparison of methods for estimating mean fecundity

Four computational methods for estimating mean fecundity are compared by Monte Carlo simulation. One of the four methods is the simple expedient of estimating fecundity at sample mean length, a method known to be downwardly biassed. The Monte Carlo study shows that the other three methods reduce bias and provide worthwhile efficiency gains. For small samples, the most efficient of the four methods is a 'bias adjustment', proposed here, that uses easily calculated sample statistics. For large samples, a numerical integration method has the highest efficiency. The fourth method, a 'direct summation' procedure which can be done easily in many statistical or spreadsheet programs, performs well for all sample sizes.     

A comparison of methods for assessing yeast viability

Summary Eight different methods were used to assess the cell viability of four strains of Saccharomyces. Staining with Mg-ANS, primuline yellow, FITC and methylene blue gave a good index of yeast cell viability. The standard plate count technique and microcolony formation also gave a good measure of cell viability. Fluorescent staining with acridine orange was the least useful of the methods tested. INT dye reduction gave a good index of respiring cells depending upon the yeast strain tested.     

A comparison of methods for predicting vegetation type

Predictive modeling of vegetation patterns has wide application in vegetation science. In this paper I discuss three methods of predictive modeling using data from the alpine treeline ecotone as a case study. The study area is a portion of Glacier National Park, Montana. Parametric general linear models (GLM), artificial neural networks (ANN) and classification tree (CT) methods of predicting vegetation type are compared to determine the relative strength of each predictive approach and how they may be used in concert to increase understanding of important vegetation – environment relations. For each predictive method, vegetation type within the alpine treeline ecotone is predicted using a suite of environmental indicator variables including elevation, moisture potential, solar radiation potential, snow potential index, and disturbance history. Results from each of the predictive methods are compared against the real vegetation types to determine the relative accuracy of the methods.When the entire data field is examined (i.e., not evaluated by smaller spatial aggregates of data) the ANN procedure produces the most accurate predictions (=0.571); the CT predictions are the least accurate (=0.351). The predicted patterns of vegetation on the landscape are considerably different using the three methods. The GLM and CT methods produce large contiguous swaths of vegetation types throughout the study area, whereas the ANN method produces patterns with much more heterogeneity and smaller patches.When predictions are compared to reality at catchment scale, it becomes evident that the accuracy of each method varies depending upon the specific situation. The ANN procedure remains the most accurate method in the majority of the catchments, but both the GLM and PCT produce the most accurate classifications in at least one basin each.The variability in predictive ability of the three methods tested here indicates that there may not be a single best predictive method. Rather it may be important to use a suite of predictive models to help understand the environment – vegetation relationships. The ability to use multiple predictive methods to determine which spatial subunits of a landscape are outliers is important when identifying locations useful for climate change monitoring studies.     

Studies on Trypanosoma vivax: comparison of parasitological diagnostic methods.

Leeflang P., Buys Janny and Blotkamp Coby. 1978. Studies on Trypanosoma vivax: comparison of parasitological diagnostic methods. International Journal for Parasitology8: 15–18. Parasitological methods for the diagnosis of Trypanosoma vivax infections in Nigerian cattle, including thin and thick blood smear and lymph gland smear examination, haematocrit centrifuge technique, hypotonie lysis test and mouse inoculation were evaluated. In 155 blood samples, thick film examination was significantly better than thin smear examination; in 126 samples, the haematocrit centrifuge technique was significantly superior over thin smear but not over thick film examination; when all six methods were applied in 52 samples, significant differences could only be demonstrated between mouse inoculation on one hand and thick film and gland smear examination, haematocrit centrifuge technique and hypotonie lysis test on the other hand, and between thin smear examination and hypotonic lysis test. It was shown that none of the tests was either satisfactory or sufficiently reliable to be used alone. The combination of either haematocrit centrifuge technique or thick film examination together with thin smear examination is recommended as most practical for the diagnosis of T. vivax infection under field conditions. The haematocrit centrifuge technique is also more advantageous because simultaneous estimation of the packed cell volume will evaluate the clinical condition of the herd. A comparison of the value of diagnostic methods for East and West African T. vivax was included in the present study.     

A framework for clinical evaluation of diagnostic technologies.

Most new diagnostic technologies have not been adequately assessed to determine whether their application improves health. Comprehensive evaluation of diagnostic technologies includes establishing technologic capability and determining the range of possible uses, diagnostic accuracy, impact on the health care provider, therapeutic impact and impact on patient outcome. Guidelines to determine whether each of these criteria have been met adequately are presented. Diagnostic technologies should be disseminated only if they are less expensive, produce fewer untoward effects and are at least as accurate as existing methods, if they eliminate the need for other investigations without loss of accuracy, or if they lead to institution of effective therapy. Establishing patient benefit often requires a randomized controlled trial in which patients receive the new test or an alternative diagnostic strategy. Other study designs are logistically less difficult but may not provide accurate assessment of benefit. Rigorous assessment of diagnostic technologies is needed for efficient use of health care resources.     

A comparison of somatotype methods

In order to compare Parnell's and Heath's somatotype methods, the authors independently somatotyped a series of 59 adult male and 61 adult female subjects, (1) using the criteria of Heath's method, (2) using the criteria of Parnell's method, and (3) taking into consideration tentatively adapted Parnell criteria in addition to Heath's criteria. The authors conclude that when use similar rating criteria their mean differences are smaller, their overall correlations are similar, and their percentage agreements to a half-unit are higher (96%) than for comparisons reported by other investigators. The study considers the potentially important relationships of measurements of subcutaneous fat to ratings of the first component. The similarity of distributions of subcutaneous fat measurements and of first component ratings in selected samples suggest important interrelationships among ratings of the first component, height/ weight ratios and subcutaneous fat measurements. The authors feel: (1) that Parnell's method fails to modify the basic weaknesses in Sheldon's somatotype method; and (2) that analyses of the anthropometric data basic to Parnell's method, if guided by the criteria of Heath's method, will further objectify and simplify Heath's method, will improve agreement among independent raters, and will increase the usefulness of somatotyping as a research instrument.     

Molecular analysis for mitochondrial DNA disorders

In this article, we review the current methodologies used for the molecular diagnosis of mitochondrial DNA defects. Definition of mitochondrial disorders at the molecular level has been difficult because of both clinical and genetic heterogeneity. Direct DNA analysis for common point mutations and large mtDNA deletions is readily performed and can be done routinely. However, a large number of patients who have the clinical manifestations and muscle pathology findings consistent with mitochondrial DNA disorders do not have detectable common mutations. Additional mutation screening methods are required for the detection of rare and previously undescribed mutations in the mitochondrial genome.     

MaxBench: evaluation of sequence and structure comparison methods

SUMMARY: MaxBench is a web-based system available for evaluating the results of sequence and structure comparison methods, based on the SCOP protein domain classification. The system makes it easy for developers to both compare the overall performance of their methods to standard algorithms and investigate the results of individual comparisons. AVAILABILITY: http://www.sanger.ac.uk/Users/lp1/MaxBench/     

A statistical method for the comparison of a discrete diagnostic test with several continuous diagnostic tests.

In this paper we study a statistic that is suitable for comparing a discrete diagnostic marker to one or more continuous diagnostic markers. Test procedures and confidence intervals are based on asymptotic normality. The statistic is applicable for correlated data in which all the markers are obtained for each subject. The statistic was studied for use in comparing two markers for rectal bleeding. Examples for this application and two more general applications are presented.