Topic
Replicate
About: Replicate is a research topic. Over the lifetime, 653 publications have been published within this topic receiving 24788 citations.
Papers published on a yearly basis
1 / 2
Papers
TL;DR: A new statistical model and computer program, replicate MATS (rMATS), designed for detection of differential alternative splicing from replicate RNA-Seq data, which uses a hierarchical model to simultaneously account for sampling uncertainty in individual replicates and variability among replicates.
Abstract: Ultra-deep RNA sequencing (RNA-Seq) has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We previously developed multivariate analysis of transcript splicing (MATS), a statistical method for detecting differential alternative splicing between two RNA-Seq samples. Here we describe a new statistical model and computer program, replicate MATS (rMATS), designed for detection of differential alternative splicing from replicate RNA-Seq data. rMATS uses a hierarchical model to simultaneously account for sampling uncertainty in individual replicates and variability among replicates. In addition to the analysis of unpaired replicates, rMATS also includes a model specifically designed for paired replicates between sample groups. The hypothesis-testing framework of rMATS is flexible and can assess the statistical significance over any user-defined magnitude of splicing change. The performance of rMATS is evaluated by the analysis of simulated and real RNA-Seq data. rMATS outperformed two existing methods for replicate RNA-Seq data in all simulation settings, and RT-PCR yielded a high validation rate (94%) in an RNA-Seq dataset of prostate cancer cell lines. Our data also provide guiding principles for designing RNA-Seq studies of alternative splicing. We demonstrate that it is essential to incorporate biological replicates in the study design. Of note, pooling RNAs or merging RNA-Seq data from multiple replicates is not an effective approach to account for variability, and the result is particularly sensitive to outliers. The rMATS source code is freely available at rnaseq-mats.sourceforge.net/. As the popularity of RNA-Seq continues to grow, we expect rMATS will be useful for studies of alternative splicing in diverse RNA-Seq projects.
2,395 citations
TL;DR: An analysis of the physiological function of the identified genes indicates that the RP approach is powerful for identifying biologically relevant expression changes and can lead to a sharp reduction in the number of replicate experiments needed to obtain reproducible results.
1,686 citations
California Institute of Technology1, Stockholm School of Economics2, University of Innsbruck3, National University of Singapore4, University of Pennsylvania5, Center for Open Science6, University of Virginia7, Harvard University8, Ludwig Maximilian University of Munich9, University of Amsterdam10, Harbin Institute of Technology11
TL;DR: It is found that peer beliefs of replicability are strongly related to replicable, suggesting that the research community could predict which results would replicate and that failures to replicate were not the result of chance alone.
Abstract: Being able to replicate scientific findings is crucial for scientific progress. We replicate 21 systematically selected experimental studies in the social sciences published in Nature and Science between 2010 and 2015. The replications follow analysis plans reviewed by the original authors and pre-registered prior to the replications. The replications are high powered, with sample sizes on average about five times higher than in the original studies. We find a significant effect in the same direction as the original study for 13 (62%) studies, and the effect size of the replications is on average about 50% of the original effect size. Replicability varies between 12 (57%) and 14 (67%) studies for complementary replicability indicators. Consistent with these results, the estimated true-positive rate is 67% in a Bayesian analysis. The relative effect size of true positives is estimated to be 71%, suggesting that both false positives and inflated effect sizes of true positives contribute to imperfect reproducibility. Furthermore, we find that peer beliefs of replicability are strongly related to replicability, suggesting that the research community could predict which results would replicate and that failures to replicate were not the result of chance alone.
1,269 citations
TL;DR: In this paper, the authors propose a unified approach to measure the reproducibility of findings identified from replicate experiments and identify putative discoveries using Reproducibility, which creates a curve, which quantitatively assesses when the findings are no longer consistent across replicates.
Abstract: Reproducibility is essential to reliable scientific discovery in high-throughput experiments. In this work we propose a unified approach to measure the reproducibility of findings identified from replicate experiments and identify putative discoveries using reproducibility. Unlike the usual scalar measures of reproducibility, our approach creates a curve, which quantitatively assesses when the findings are no longer consistent across replicates. Our curve is fitted by a copula mixture model, from which we derive a quantitative reproducibility score, which we call the “irreproducible discovery rate” (IDR) analogous to the FDR. This score can be computed at each set of paired replicate ranks and permits the principled setting of thresholds both for assessing reproducibility and combining replicates. Since our approach permits an arbitrary scale for each replicate, it provides useful descriptive measures in a wide variety of situations to be explored. We study the performance of the algorithm using simulations and give a heuristic analysis of its theoretical properties. We demonstrate the effectiveness of our method in a ChIP-seq experiment.
1,003 citations
TL;DR: This work proposes a unified approach to measure the reproducibility of findings identified from replicate experiments and identify putative discoveries using reproducible discoveries, which creates a curve, which quantitatively assesses when the findings are no longer consistent across replicates.
Abstract: Reproducibility is essential to reliable scientific discovery in high-throughput experiments. In this work we propose a unified approach to measure the reproducibility of findings identified from replicate experiments and identify putative discoveries using reproducibility. Unlike the usual scalar measures of reproducibility, our approach creates a curve, which quantitatively assesses when the findings are no longer consistent across replicates. Our curve is fitted by a copula mixture model, from which we derive a quantitative reproducibility score, which we call the "irreproducible discovery rate" (IDR) analogous to the FDR. This score can be computed at each set of paired replicate ranks and permits the principled setting of thresholds both for assessing reproducibility and combining replicates. Since our approach permits an arbitrary scale for each replicate, it provides useful descriptive measures in a wide variety of situations to be explored. We study the performance of the algorithm using simulations and give a heuristic analysis of its theoretical properties. We demonstrate the effectiveness of our method in a ChIP-seq experiment.
934 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2026 | 5 |
| 2025 | 285 |
| 2024 | 363 |
| 2023 | 722 |
| 2022 | 1,566 |
| 2021 | 221 |