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Results for “Reproducibility”

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At least 19 recordsLinked to original sources

PubMed2025

Reproducibility of genetic risk factors identified for long COVID using combinatorial analysis across US and UK patient cohorts with diverse ancestries.

BACKGROUND: Long COVID is a major public health burden causing a diverse array of debilitating symptoms in tens of millions of patients globally. In spite of this overwhelming disease prevalence, staggering cost, severe impact on patients' lives and intense global research efforts, study of the disease has proved challenging due to its complexity. Genome-wide association studies (GWAS) have identified only four loci potentially associated with the disease, although these results did not statistically replicate between studies. A previous combinatorial analysis study identified a total of 73 genes that were highly associated with two long COVID cohorts in the predominantly (> 91%) white European ancestry Sano GOLD population, and we sought to reproduce these findings in the independent and ancestrally more diverse All of Us (AoU) population. METHODS: We assessed the reproducibility of the 5343 long COVID disease signatures from the original study in the AoU population. Because the very small population sizes provide very limited power to replicate findings, we initially tested whether we observed a statistically significant enrichment of the Sano GOLD disease signatures that are also positively correlated with long COVID in the AoU cohort after controlling for population substructure. RESULTS: For the Sano GOLD disease signatures that have a case frequency greater than 5% in AoU, we consistently observed a significant enrichment (77-83%, p < 0.01) of signatures that are also positively associated with long COVID in the AoU cohort. These encompassed 92% of the genes identified in the original study. At least five of the disease signatures found in Sano GOLD were also shown to be individually significantly associated with increased long COVID prevalence in the AoU population. Rates of signature reproducibility are strongest among self-identified white patients, but we also observe significant enrichment of reproducing disease associations in self-identified black/African-American and Hispanic/Latino cohorts. Signatures associated with 11 out of the 13 drug repurposing candidates identified in the original Sano GOLD study were reproduced in this study. CONCLUSION: These results demonstrate the reproducibility of long COVID disease signal found by combinatorial analysis, broadly validating the results of the original analysis. They provide compelling evidence for a much broader array of genetic associations with long COVID than previously identified through traditional GWAS studies. This strongly supports the hypothesis that genetic factors play a critical role in determining an individual's susceptibility to long COVID following recovery from acute SARS-CoV-2 infection. It also lends weight to the drug repurposing candidates identified in the original analysis. Together these results may help to stimulate much needed new precision medicine approaches to more effectively diagnose and treat the disease. This is also the first reproduction of long COVID genetic associations across multiple populations with substantially different ancestry distributions. Given the high reproducibility rate across diverse populations, these findings may have broader clinical application and promote better health equity. We hope that this will provide confidence to explore some of these mechanisms and drug targets and help advance research into novel ways to diagnose the disease and accelerate the discovery and selection of better therapeutic options, both in the form of newly discovered drugs and/or the immediate prioritization of coordinated investigations into the efficacy of repurposed drug candidates.

Humans↗

PubMed1992

[Poor reproducibility of parameters of heart rate variations].

The analysis of heart rate variability is supposed to be a marker of autonomic cardiac activity and is used for risk stratification of post-infarction patients. Analysis of heart rate variability in the frequency domain may permit a differentiation of vagal and sympathetic control; for such analyses only short time intervals characterized by a steady-state autonomic balance can be used. Yet, it is unclear whether single determinations of heart rate variability indices derived from short time intervals yield reproducible results. Therefore, the reproducibility of heart rate variability indices was studied with weekly measurements in 10 healthy volunteers under the following defined conditions: 13 min supine rest, 10 min standing, 13 min sitting, and 15 min cycle ergometry followed by a 14 min recovery period. Heart rate variability was determined in the frequency domain (fast Fourier transformation) and in the time domain. The reproducibility was estimated by the coefficient of variation (CV). Additionally, the reproducibility of heart rate, blood pressure, and the expiratory-inspiratory ratio of heart rate was determined. The reproducibility of the frequency domain indices (36.6-74.9% CV) and of the time domain indices (19.6-32.8% CV) was considerably worse than that of heart rate (5.2-8.2% CV), blood pressure (5.1-8.2% CV) and the expiratory-inspiratory ratio of heart rate (4.6% CV). The reproducibility of heart rate variability indices was not improved by orthostatic or ergometric challenge. This poor reproducibility does not permit a reliable interpretation of heart rate variability on the basis of single measurements in healthy volunteers. Given the wide range and scatter of the measured parameters, the diagnostic and prognostic value of heart rate variability indices derived from short recording periods appears questionable.

Arrhythmias, Cardiac↗

PubMed1976

Prevalence and reproducibility of exercise-induced ventricular arrhythmias during maximal exercise testing in normal men.

The occurrence of ventricular arrhythmias at rest or during ordinary daily activities has been implicated as a risk factor for future coronary-related events and sudden death. However, the clerical significance of exercise-induced ventricular arrhythmias remains uncertain. To assess the prevalence and reproducibility of such arrhythmias, two serial maximal treadmill exercise tests were performed in a study population of 543 male Indian State policemen at an average interval of 2.9 years. Four hundred sixty-two subjects were clinically free of evidence of cardiovascular disease, and 81 had evidence of definite or suspected cardiovascular disease. The prevalence of exercise-induced ventricular arrhythmias during the first test was 30% in men aged 25 to 34 years, 32% in those aged 35 to 44 years and 36% in those aged 45 to 54 years. The prevalence rate in these age groups with repeat testing was 36, 38 and 42%, respectively. These differences were not statistically significant. The group with definite or suspected cardiovascular disease had a greater prevalence of exercise-induced ventricular arrhythmias than normal subjects during both tests but the prevalence rate with repeat testing remained constant. The occurrence of exercise-induced ventricular arrhythmias was reproducible in individual subjects during the second test in 55% of 25 to 34 year olds, 58% of 35 to 44 year olds and 62% of 45 to 54 year olds. Thus, individual reproducibility in two consecutive tests was only slightly greater than reproducibility by chance alone. The group with known or suspected cardiovascular disease demonstrated a trend toward greater reproducibility with repeat testing. Exercise-induced ventricular arrhythmias were not reproducible by type or complexity. The marked variability of exercise-induced ventricular arrhythmias during repeat maximal exercise testing in a clinically normal population appears to negate the usefulness of this finding during a single test as a marker of future cardiovascular disease. Nevertheless, subjects whose arrhythmias were reproducible may form a group destined to manifest clinical cardiovascular disease in long-term follow-up studies.

Adult↗

PubMed2026

Bit-reproducible parallel phylogenetic tree inference.

MOTIVATION: Phylogenetic trees describe the evolutionary history among biological species based on their genomic data. Maximum likelihood (ML) based phylogenetic inference tools search for the tree and evolutionary model that best explain the observed genomic data. Given the independence of likelihood score calculations between different genomic sites, parallel computation is commonly deployed. This is followed by a parallel summation over the per-site scores to obtain the overall likelihood score of the tree. However, basic arithmetic operations on IEEE 754 floating-point numbers, such as addition and multiplication, inherently introduce rounding errors. Consequently, the order by which floating-point operations are executed affects the exact resulting likelihood value since these operations are not associative. Moreover, parallel reduction algorithms in numerical codes re-associate operations as a function of the core count and cluster network topology, inducing different round-off errors. These low-level deviations can cause heuristic searches to diverge and induce high-level result discrepancies (e.g. yield topologically distinct phylogenies). This effect has also been observed in multiple scientific fields beyond phylogenetics. RESULTS: We observe that varying the degree of parallelism results in diverging phylogenetic tree searches (high-level results) for over 31% out of 10 179 empirical datasets. More importantly, 8% of these diverging datasets yield trees that are statistically significantly worse than the best-known ML tree for the dataset (AU-test, P < .05). To alleviate this, we develop a variant of the widely used phylogenetic inference tool RAxML-NG, which does yield bit-reproducible results under varying core-counts, with a slowdown of only 0%-12.7% (median 0.8%) on up to 768 cores. For this, we introduce the ReproRed reduction algorithm, which yields bit-identical results under varying core-counts, by maintaining a fixed operation order that is independent of the communication pattern. ReproRed is thus applicable to all associative reduction operations-in contrast to competitors, which are confined to summation. Our ReproRed reduction algorithm only exchanges the theoretical minimum number of messages, overlaps communication with computation, and utilizes fast base-cases for local reductions. ReproRed is able to all-reduce (via a subsequent broadcast) 4.1×106 operands across 48-768 cores in 19.7-48.61 μs, thereby exhibiting a slowdown of 13%-93% over a non-reproducible all-reduce algorithm. ReproRed outperforms the state-of-the-art reproducible all-reduction algorithm ReproBLAS (offers summation only) beyond 10 000 elements per core. In summary, we re-assess non-reproducibility in parallel phylogenetic inference, present the first bit-reproducible parallel phylogenetic inference tool, as well as introduce a general algorithm and open-source code for conducting reproducible associative parallel reduction operations. AVAILABILITY AND IMPLEMENTATION: ReproRed: https://doi.org/10.5281/zenodo.15004918 (LGPL)-Reproducible RAxML-NG version https://doi.org/10.5281/zenodo.15017407 (GPL).

Phylogeny↗

PubMed1992

Reproducibility of measurements of coronary narrowings by videodensitometry and by digital calipers.

Computer-assisted videodensitometry has been shown to be a reliable and reproducible method of measuring absolute and relative coronary narrowings. Using a commercially available analyzer (Vanguard XR70) we confirmed intra- and interobserver reproducibilities in 34 narrowings in 9 patients. Analyses were performed on normal area and diameter, stenotic area and diameter, percent area stenosis and percent diameter stenosis. For all 6 analyses, excellent intra- and interobserver correlations were found (r = 0.93-0.98), with slopes close to 1 and intercepts close to zero. Caliper measurements (Mitutoyo Digimatic) of the same lesions by the same observers showed good inter- and intraobserver reproducibility for percent diameter stenosis (r = 0.90 and 0.86), with mean interobserver difference of 1.67 +/- (SD) 6.4% and intraobserver difference of 2.97 +/- (SD) 7.9%. However, less good correlations were found between caliper and videodensitometric measurements of percent diameter stenosis; r = 0.61 and 0.76 for the two observers. These data suggest that videodensitometry is a highly reproducible quantitative angiographic method, suitable for documenting changes in the severity of coronary artery lesions, both spontaneous or related to interventions. Caliper measurements do not provide the same degree of accuracy, but they have acceptable reproducibility in measuring diameter stenosis. As such, they are also suitable for assessing changes in severity of coronary artery lesions in individual patients.

Angioplasty, Balloon, Coronary↗

PubMed1979

Reproducibility of exercise-induced ventricular arrhythmia after myocardial infarction.

To evaluate the reproducibility of exercise-induced ventricular arrhythmia, 155 men with a mean age of 53 +/- 8 years underwent serial exercise testing 3 to 52 weeks after myocardial infarction. The reproducibility of categorical test responses, that is, the presence or absence of ventricular arrhythmia, was evaluated with the kappa coefficient, which considers negative as well as possible test responses and expresses reproducibility above the chance level. Reproducibility was highest at an intertest interval of 1 to 5 days and was not enhanced by further categorizing premature ventricular complexes as simple or complex based on their frequency or configuration. Continuous response measures such as frequency of premature ventricular complexes yielded higher reproducibility than categorical responses. Continuous response measures appear preferable to categorical responses for evaluating the clinical significance and response to antiarrhythmic therapy of ventricular arrhythmias.

Arrhythmias, Cardiac↗

PubMed1978

Effects of occlusal therapy on pantographic reproducibility of mandibular border movements.

A clinical experiment was undertaken to study the relationship between occlusal therapy and pantographic reproducibility. Twenty-six subjects were categorized according to their ability to reproduce pantographic border movements and were put into either a control nonreproducible, control reproducible, or experimental nonreproducible group. From each subject a sequence of five pantographic surveys consisting of two morning and two afternoon pantographic recordings was taken. Each survey period lasted a minimum of 30 days. The experimental subjects alone were given occlusal splint therapy and occlusal adjustment therapy during the sequence of recall periods. The relationship between the effect caused by occlusal therapy and pantographic reproducibility was analyzed. For the purpose of analysis, the pantographic recordings were assessed a numerical score using a pantographic reproducibility index. A double-blind technique was used until all data were collected.

Adult↗

PubMed1977

Measurement of hemagglutination-inhibiting antibody to influenza virus in the 1976 influenza vaccine program: methods and test reproducibility.

Titers of hemagglutination-inhibiting (HAI) antibody were determined for all sera obtained from participants in the 1976 Influenza Vaccine Test Program. At least eight control sera were included in each test during the vaccine trial period for the purpose of monitoring HAI test reproducibility. Estimates of day-to-day reproducibility were defined as the percentages of duplicate aliquots of the same sera, tested on two separate days, having HAI antibody titers that did not differ by more than one twofold dilution. These reproducibility estimates ranged from 89% to 97% with influenza A/New Jersey/76 and A/Mayo Clinic/74 antigens. In contrast, within-day reproducibility estimates obtained from all sets of control sera ranged from 96% to 98%. Estimates of day-to-day test reproducibility obtained with selected sera taken after vaccination that were titrated on two differen days ranged from 90% to 98%. Geometric mean titers of these sera tested weeks or months apart differed on some occasions during the test period.

Antibodies, Viral↗

PubMed1975

Reproducibility of the analytab (API 20E) system.

The reproducibility of the Analytab (API 20E) system for identification of Enterobacteriaceae was evaluated with 110 clinical isolates. Each isolate was identified by two technologists at different times. Genus-species identification was 97.3% reproducible; however, only 55.5% of the strains gave identical reactions in all 20 of the API 20E biochemical tests on repeat testing. Of those strains which varied, 56% possessed only one variable biochemical test. The reproducibility for each biochemical test was calculated and ranged from 89 to 100%. A subset of 20 of the most variable strains was tested further under conditions of varying incubation time (15 and 22 h) and inoculum concentration (10(7), 10(5), and 10(3) colony-forming units per ml), and by having four technologists interpret the test results. The reproducibility for each biochemical test for these 20 variable strains ranged from 86 to 99%. Less variation in interpretation by technologists was seen at an incubation time of 22 h and an inoculum concentration of 10(7) colony-forming units per ml. Consideration of the reproducibility for each biochemical test can aid in determining the probability that two isolates suspected of being the same strain, but with API profiles which differ by one or more biochemical test results, are in fact the same strain. Variables such as inoculum size, incubation time, technologist interpretation, and strip variability affect the API test results and should be standardized to minimize their effects.

Bacteriological Techniques↗

PubMed1977

Epidemiological evaluation of funduscopic findings in cerebrovascular diseases. III. Observer variability and reproducibility for funduscopic findings.

In order to evaluate observer variability and reproducibility for the funduscopic findings, the color slides of one hundred cases in Akabane and Asahi town in Japan were investigated and the following were revealed: 1. Observer variability for Keith-Wagener's classification was the least in the grade 3 and the most in grade 0. The variability of diagnosis between observers was the least for retinal bleeding and the most for anteriolar reflex and remarkable for lateral displacement and arteriolar narrowing. In general, the observe variability was one grade at most. 2. Reproducibility for Scheie's hypertensive classification was 73 per cent and that for Scheie's arteriosclerotic and Keith-Wagner's classifications was 66 per cent. Fairly good reproducibility was observed in retinal bleeding and poor reproducibility in arteriolar reflex and vertical and lateral displacements, In general, the intra-observer variability for the funduscopic findings was one grade at most. 3. Observer variability and reproducibility for the funduscopic findings would be improved by establishment of the detailed diagnostic criteria of various funduscopic findings, taking color pictures in focus and systematic training for the fresh doctors or technicians without enough experience. 4. The cases with definite narrowing of arteriole revealed smaller A/V ratio than 0.70.

Adult↗

PubMed2026

Assessing reproducibility of Hi-C chromatin interactions using stratum-adjusted irreproducible discovery rate.

MOTIVATION: Hi-C is a powerful technology for mapping chromatin interactions genome-wide. However, interaction loops identified from Hi-C contact maps often vary across replicate experiments due to experimental noise, making reproducibility assessment essential. A major challenge lies in the genomic distance dependence of interaction strength, which systematically affects reproducibility but is overlooked by existing methods for reproducibility assessment. RESULTS: We introduce Stratum-Adjusted Irreproducible Discovery Rate (SIDR), a novel statistical model that integrates distance stratification into the widely-used Irreproducible Discovery Rate (IDR) framework. SIDR explicitly models the confounding effect of genomic distance, enabling global control of irreproducibility across interaction ranges. Through simulations and real Hi-C datasets, we demonstrate that SIDR improves discriminative power and recovers more biologically meaningful interactions than existing approaches, making it a valuable tool for robust and reproducible Hi-C analysis. AVAILABILITY: The R package SIDR is freely available on GitHub https://github.com/qunhualilab/SIDR.

Chromatin↗

PubMed1979

The reproducibility of pantographic tracings on medicated and nonmedicated subjects.

Tracings were made on three patients using a modified pantographic device. The tracings were made on glass flags with wax, etched, and superimposed. The effects of body position and modification were investigated. From this research project the following can be concluded: 1. A precise method has been developed which permits superimposition of pantographic tracings for analysis. 2. There is a significant difference in reproducibility between medicated and nonmedicated subjects. 3. The percentage coincidence of border tracings increases significantly when the patient is pantographed while under the influence of medication (Valium). 4. The angulation of the body does not appear to be significant for reproducing border tracings. 5. There appears to be no significant difference in the reproducibility of the border tracings relative to time (1, 1 1/2, 2, and 2 1/2 hours) after medication. 6. The lateral side shift of the jaw cannot always be reproduced accurately. 7. The neuromusculature appears to be the overriding factor governing border movements.

Adolescent↗

PubMed1978

Reproducibility and comparative analysis of repeated intravenous and oral glucose tolerance tests.

We have developed a methodology for measuring the reproducibility of the oral glucose tolerance test (OGTT) and the intravenous glucose tolerance test (IVGTT) in normal subjects and in offspring of conjugal diabetic parents. Both groups of subjects revealed more striking correlations of several parameters of blood glucose and insulin secretion between two IVGTTs than between two OGTTs. Employing arbitrary criteria, we calculated a "reproducibility index" as a quantitative measure of blood glucose variability in each subject. No significant difference was found in the reproducibility of OGTT versus IVGTT, nor in normals versus the offspring. Only about 50 per cent of the tests in normals and in the offspring could be considered to be "reproducible." The offspring revealed greater correlations of several parameters, particularly insulin secretion, between the two IVGTTs and between the two OGTTs as compared with the normal group. However, the blood glucose variations tended to be considerably greater in the offspring from one to the other test.

Administration, Oral↗

PubMed1978

Reproducibility of regional cerebral blood flow measurements in acute severe head injury.

In order to evaluate the reproducibility of regional cerebral blood flow (rCBF) measurements in pathological brain tissue, serial measurements were carried out in 13 determinations performed in patients who were comatose after severe head injuries within the first 2 weeks after the head trauma. The xenon-133 intra-arterial method was used for the flow measurements, and the flow was studied separately in 16 areas of the brain, producing 197 regional double determinations. The patients were maintained in a steady state during and between the measurements, and only differences of less than 2 mm Hg in the arterial CO2 pressure and less than 5 mm Hg in the perfusion pressure were tolerated. The reproducibility was found to be reasonably good as regards initial slope-flow indices and height/area flow indices and height/area flow values, whereas that of the compartmentally calculated flow parameters was poorer. On dividing the series into severely and moderately pathological areas, it could be shown that the reproducibility of the flor values in the moderately pathological brain areas was acceptable and similar to the results reported by others, whereas the reproducibility in the most severely pathological areas of the brain was rather poor, as regards the flow in the fast compartments. The correlation between the various flow parameters was found to be fairly good.

Brain Injuries↗

PubMed1975

Inter-examiner and intra-examiner reproducibility in clinical and radiographic diagnosis.

The first technical report to be published by the FDI considered the principal requirements for controlled clinical trials of caries preventive agents and procedures. This document advocated the use of a simple reproducibility ratio as a measure of variability in caries diagnosis. In accordance with the FDI recommendations available figures from published work on duplicated examinations are presented in terms of this reproducibility ratio. The data refers to intra- and inter-examiner variability with respect to both clinical and radiographic examinations. Reproducibility studies carried out as a pre-calibration investigation and during the baseline examinations of a current clinical trial are also included. Considerable diversity is apparent, the intra- and inter-examiner variation for clinical examinations ranging from 0-13 to 0-61, and for radio-graphic assessments from 0-06 to 0-60. If an acceptable range of reproducibility ratios is to be formulated then this wide variation will have to be taken into account. Ultimately, if examiner variability cannot be maintained within reasonable limits, then the choice of an examiner could be just as important as the choice of the test substance.

Child↗

PubMed1977

[The reproducibility of occlusal contacts in the Dentatus and Stuart articulators].

The reproducibility of occlusal contacts of 30 subjects was tested in the Dentatus and Stuart articulators. Primary contacts in the terminal hinge axis position were reliably reproducible in both articulators. Contacts in habitual intercuspidation were reproduced only approximately by both devices. Contacts in eccentric occlusion were satisfactorily reproduced in the Stuart articulator only. The findings show that doubts are indicated about the simulating capacity of semi-adjustable articulators which is frequently rated too high.

Dental Articulators↗

PubMed2026

2-Mercaptoethanol/DMSO Workflow Enables Highly Reproducible Quantitative Proteomics.

Proteomics provides a systematic and high-throughput approach to comprehensively characterize protein networks, enabling insights into cellular functions and disease mechanisms. Carbamidomethylation using iodoacetamide (IAA), a common method for cysteine alkylation, is known to cause nonspecific modifications that increase spectral complexity in mass spectrometry and reduce quantitative accuracy. Here, we established a reproducibility-focused 2-mercaptoethanol (2-ME)/dimethyl sulfoxide (DMSO) workflow and systematically evaluated its quantitative performance at the proteome-wide level. Mouse liver proteomes were processed using either 2-ME/DMSO or conventional IAA treatment, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The optimized 2-ME treatment increased the number of cysteine-modified peptides by 1.6- to 1.9-fold. Although total protein identifications were comparable, 77% of proteins exhibited improved sequence coverage with the optimized 2-ME treatment. Quantitative reproducibility was also enhanced, with the peptide quantified CV ≤ 20% increasing from 61.4% with IAA treatment to 86.1% with 2-ME treatment, and protein quantified CV ≤ 20% increasing from 80.6% with IAA treatment to 93.5% with 2-ME treatment. Application of this new workflow to ovarian clear cell carcinoma reliably detected cisplatin-induced alterations. The 2-ME/DMSO workflow offers a simple and highly reproducible proteomics strategy for accurate quantitative proteomics.

Animals↗

PubMed2025

LimROTS: a hybrid method integrating empirical Bayes and reproducibility-optimized statistics for robust differential expression analysis.

MOTIVATION: Differential expression analysis plays a vital role in omics research enabling precise identification of features that associate with different phenotypes. This process is critical for uncovering biological differences between conditions, such as disease versus healthy states. In proteomics, several statistical methods have been used, ranging from simple t-tests to more advanced methods like DEqMS, limma and ROTS. However, a flexible method for reproducibility-optimized statistics tailored for clinical omics data has been lacking. RESULTS: In this study, we developed LimROTS, a hybrid method that integrates a linear regression model and the empirical Bayes approach with reproducibility optimized statistics, to create a novel moderated ranking statistic, for robust and flexible analysis of proteomics data. We validated its performance using twenty-one proteomics gold standard spike-in datasets with different protein mixtures, MS instruments, and techniques for benchmarking. This hybrid approach improves accuracy and reproducibility of complex proteomics data, making LimROTS a powerful tool for high-dimensional omics data analysis. AVAILABILITY AND IMPLEMENTATION: LimROTS has been implemented as an R/Bioconductor package, available at https://doi.org/doi:10.18129/B9.bioc.LimROTS. Additionally, the code used in this study is available in GitHub repository https://github.com/AliYoussef96/LimROTSmanuscript.

Bayes Theorem↗