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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 (>&#x2009;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&#x2009;<&#x2009;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↗
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&#xa0;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&#x2009;<&#x2009;.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&#xd7;106 operands across 48-768 cores in 19.7-48.61&#x2009;&#x3bc;s, 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&#xa0;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↗
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↗
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↗
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 &#x2264; 20% increasing from 61.4% with IAA treatment to 86.1% with 2-ME treatment, and protein quantified CV &#x2264; 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↗
PubMed2025

Breaking the reproducibility barrier with standardized protocols for plant-microbiome research.

Inter-laboratory replicability is crucial yet challenging in microbiome research. Leveraging microbiomes to promote soil health and plant growth requires understanding underlying molecular mechanisms using reproducible experimental systems. In a global collaborative effort involving five laboratories, we aimed to help advance reproducibility in microbiome studies by testing our ability to replicate synthetic community assembly experiments. Our study compared fabricated ecosystems constructed using two different synthetic bacterial communities, the model grass Brachypodium distachyon, and sterile EcoFAB 2.0 devices. All participating laboratories observed consistent inoculum-dependent changes in plant phenotype, root exudate composition, and final bacterial community structure, where Paraburkholderia sp. OAS925 could dramatically shift microbiome composition. Comparative genomics and exudate utilization linked the pH-dependent colonization ability of Paraburkholderia, which was further confirmed with motility assays. The study provides detailed protocols, benchmarking datasets, and best practices to help advance replicable science and inform future multi-laboratory reproducibility studies.

Plants↗
PubMed1979

Neocortical pyramidal cells: a model with dendritic calcium conductance reproduces repetitive firing and epileptic behavior.

A computer model of a neocortical pyramidal cell has been constructed using ideas similar to those used for hippocampal pyramidal cells. This model has been applied to the study of (a) repetitive firing, and (b) the paroxysmal depolarizing shift (PDS), an important intracellular event during seizures. Although calcium spikes have not been demonstrated directly in neocortical cells, we have postulated (by analogy with hippocampal pyramidal cells) a dendritic calcium conductance and a 'slow potassium' conductance modulated by intracellular calcium ion. With these dendritic ionic conductances, the model is able to reproduce the following experimental features of neocortical pyramidal cells: the afterdepolarization and succeeding afterhyperpolarization after an antidromic spike, and the f-I (firing rate-injected current) curve. Some of the differences between 'fast' and 'slow' pyramidal tract neurons (PTNs) -- narrower spikes and a steeper f-I curve in the fast PTNs -- may be explained by differences in Hodgkin-Huxley potassium kinetics between the two kinds of cell. The same model which faithfully reproduces repetitive firing behavior also reproduces (given appropriate synaptic inputs) the following intracellular events recording during epileptic seizures: (a) a burst of action potentials superimposed on and followed by a PDS, and (b) rapid repetitive firing succeeded by an IPSP. Thus, a single set of parameters can reporduce both normal physiological behavior and 'epileptic' behavior: the particular behavior seen depending on how the cell is stimulated. This overall result is the same as for our model of the CA1 hippocampal cell. It suggests that certain acutely acting epileptogenic agents, e.g. penicillin, may act by increasing synaptic input (perhaps both excitatory and inhibitory) to pyramidal cells, rather than by altering their membrane properties. As in our CA1 hippocampal cell model, bursting seems to be a phenomenon generated by the apical dendrite.

Biophysical Phenomena↗
PubMed1976

Cytotoxic testing for food allergy: evaluation of reproducibility and correlation.

Cytotoxic food tests still present conflicting opinions concerning their validity. Nine atopic patients with or without a history of food allergy were studied along with 5 nonatopic patients. All tests were conducted in a double-blind fashion with 6 determinations for each of 10 food antigens. Reproducibility of the test (5/6 positive or negative) was demonstrated with wheat, milk, yeast, chocolate, and orange. In the nonatopic group, reproducible results were obtained for wheat, egg, yeast, chocolate, and chicken. Clinical correlation with 11 foods in 7 patients was demonstrated. However, there were 46 positive tests without correlation and 2 negative tests with positive histories. Therefore, there appears to be reproducibility of the tests to only 3 foods but no apparent correlation with clinical symptoms. At the present time, cytotoxic tests offer no reliable help in establishing the diagnosis of food allergy.

Animals↗
PubMed2026

Challenges for reproducibility in species delimitation.

Species richness is a foundational metric for comparing biodiversity among clades and regions in ecology, evolution, and conservation. As the biodiversity crisis accelerates, taxonomists face increasing pressure to delimit and name species rapidly, often relying on automated or semi-automated methods that prioritize speed over thoroughness. Yet the reproducibility of species delimitation (the degree to which independent experts reach consistent conclusions given the same evidence) remains largely unquantified, and its consequences for estimates of species richness have never been assessed at the scale of an entire fauna. This gap is consequential: if species delimitation is highly variable among practitioners, then published species counts may reflect the idiosyncrasies of individual taxonomists as much as the true biological structure of diversity within and among clades. Here we evaluate the precision, or reproducibility, of species delimitation in Neotropical freshwater fishes, the most species-rich continental vertebrate assemblage. We provided identical morphological and molecular datasets for species representing four genera to 40 taxonomic experts (10 per genus), who were asked to delimit species using (1) their preferred analytical approaches and (2) standardized analytical outputs. Total variance in species delimitation was partitioned into variance attributable to data analysis and interpretation of results. Total discordance was high (35.0%), and although standardization of analytical methods reduced discordance, substantial variance remained (23.5%) due to interpretative differences. Deviations from modal species estimates were not explained by any of seven expert attributes assessed, including taxonomic experience, publication record, geographic location, taxonomic concepts, or analytical methods. These results demonstrate that species delimitation can be subject to considerable subjectivity, even among experienced taxonomists working with identical data. Improving the precision of species delimitation will require coordinated advances across the full taxonomic workflow, including greater standardization of data acquisition and analysis, and clearer interpretative frameworks that explicitly define the evidentiary thresholds required to recognize species boundaries. Community-wide adoption of transparent reporting standards, analogous to those developed in genomics and clinical research, would help expose the sources of interpretative disagreement and facilitate more consistent application of species concepts across taxa and research groups. Developing benchmark datasets and shared reference taxonomies, against which new delimitation hypotheses can be evaluated, represents a tractable near-term goal for the systematic community. Ultimately, however, reproducible taxonomy cannot be achieved through procedural standardization alone. High-quality revisionary taxonomy must be grounded in experienced character evaluation and homology assessment, concept delimitation, and contingent analytical judgment, skills that are developed over years of immersive engagement with natural history collections, primary literature, and fieldwork. The decline of training opportunities in classical systematics therefore poses a direct threat not only to taxonomic productivity but to taxonomic consistency. Continued investment in a well-trained community of systematists, supported by institutions, collections, and funding agencies, remains the most reliable foundation for consistent and accurate species delimitation. Our results underscore that biodiversity metrics widely used in ecology, conservation planning, and macroevolutionary research are sensitive to practitioner variation in ways that have not previously been quantified, and that addressing this variation requires both methodological reform and sustained commitment to systematic expertise.

biodiversity↗