Making the cut: improved ranking and selection for large-scale inference.
Ontology highlight
ABSTRACT:
SUBMITTER: Henderson NC
PROVIDER: S-EPMC4996506 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC6553469 | biostudies-literature
Project description:As the use of large-scale data-driven analysis becomes increasingly common, the need for robust methods for interpreting a large number of results increases. To date, neuroimaging attempts to interpret large-scale activity or connectivity results often turn to existing neural mapping based on previous literature. In case of a large number of results, manual selection or percent of overlap with existing maps is frequently used to facilitate interpretation, often without a clear statistical justification. Such methodology holds the risk of reporting false positive results and overlooking additional results. Here, we propose using enrichment analysis for improving the interpretation of large-scale neuroimaging results. We focus on two possible cases: position group analysis, where the identified results are a set of neural positions; and connection group analysis, where the identified results are a set of neural position-pairs (i.e. neural connections). We explore different models for detecting significant overrepresentation of known functional brain annotations using simulated and real data. We implemented our methods in a tool called RichMind, which provides both statistical significance reports and brain visualization. We demonstrate the abilities of RichMind by revisiting two previous fMRI studies. In both studies RichMind automatically highlighted most of the findings that were reported in the original studies as well as several additional findings that were overlooked. Hence, RichMind is a valuable new tool for rigorous inference from neuroimaging results.
| S-EPMC4959697 | biostudies-literature
Project description:Quantile regression is a powerful tool for learning the relationship between a response variable and a multivariate predictor while exploring heterogeneous effects. This paper focuses on statistical inference for quantile regression in the "increasing dimension" regime. We provide a comprehensive analysis of a convolution smoothed approach that achieves adequate approximation to computation and inference for quantile regression. This method, which we refer to as conquer, turns the non-differentiable check function into a twice-differentiable, convex and locally strongly convex surrogate, which admits fast and scalable gradient-based algorithms to perform optimization, and multiplier bootstrap for statistical inference. Theoretically, we establish explicit non-asymptotic bounds on estimation and Bahadur-Kiefer linearization errors, from which we show that the asymptotic normality of the conquer estimator holds under a weaker requirement on dimensionality than needed for conventional quantile regression. The validity of multiplier bootstrap is also provided. Numerical studies confirm conquer as a practical and reliable approach to large-scale inference for quantile regression. Software implementing the methodology is available in the R package conquer.
| S-EPMC9912996 | biostudies-literature
Project description:Power and reproducibility are key to enabling refined scientific discoveries in contemporary big data applications with general high-dimensional nonlinear models. In this paper, we provide theoretical foundations on the power and robustness for the model-X knockoffs procedure introduced recently in Candès, Fan, Janson and Lv (2018) in high-dimensional setting when the covariate distribution is characterized by Gaussian graphical model. We establish that under mild regularity conditions, the power of the oracle knockoffs procedure with known covariate distribution in high-dimensional linear models is asymptotically one as sample size goes to infinity. When moving away from the ideal case, we suggest the modified model-X knockoffs method called graphical nonlin-ear knockoffs (RANK) to accommodate the unknown covariate distribution. We provide theoretical justifications on the robustness of our modified procedure by showing that the false discovery rate (FDR) is asymptotically controlled at the target level and the power is asymptotically one with the estimated covariate distribution. To the best of our knowledge, this is the first formal theoretical result on the power for the knockoffs procedure. Simulation results demonstrate that compared to existing approaches, our method performs competitively in both FDR control and power. A real data set is analyzed to further assess the performance of the suggested knockoffs procedure.
| S-EPMC7394464 | biostudies-literature
Project description:BackgroundRecently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space.ResultsIn this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into [Formula: see text] subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to [Formula: see text] families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with [Formula: see text], when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the [Formula: see text] algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with [Formula: see text]. Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at https://gitlab.ub.uni-bielefeld.de/gi/FFGC or as a Conda package at https://anaconda.org/bioconda/ffgc .
| S-EPMC10540461 | biostudies-literature
Project description:The growing number of available treatment options has led to urgent needs for reliable answers when choosing the best course of treatment for a patient. As it is often infeasible to compare a large number of treatments in a single randomized controlled trial, multivariate network meta-analyses (NMAs) are used to synthesize evidence from trials of a subset of the treatments, where both efficacy and safety related outcomes are considered simultaneously. However, these large-scale multiple-outcome NMAs have created challenges to existing methods due to the increasing complexity of the unknown correlations between outcomes and treatment comparisons. In this paper, we proposed a new framework for PAtient-centered treatment ranking via Large-scale Multivariate network meta-analysis, termed as PALM, which includes a parsimonious modeling approach, a fast algorithm for parameter estimation and inference, a novel visualization tool for presenting multivariate outcomes, termed as the origami plot, as well as personalized treatment ranking procedures taking into account the individual's considerations on multiple outcomes. In application to an NMA that compares 14 treatment options for labor induction, we provided a comprehensive illustration of the proposed framework and demonstrated its computational efficiency and practicality, and we obtained new insights and evidence to support patient-centered clinical decision making.
| S-EPMC11257173 | biostudies-literature
Project description:MotivationA promising class of methods for large-scale population genomic inference use the conditional sampling distribution (CSD), which approximates the probability of sampling an individual with a particular DNA sequence, given that a collection of sequences from the population has already been observed. The CSD has a wide range of applications, including imputing missing sequence data, estimating recombination rates, inferring human colonization history and identifying tracts of distinct ancestry in admixed populations. Most well-used CSDs are based on hidden Markov models (HMMs). Although computationally efficient in principle, methods resulting from the common implementation of the relevant HMM techniques remain intractable for large genomic datasets.ResultsTo address this issue, a set of algorithmic improvements for performing the exact HMM computation is introduced here, by exploiting the particular structure of the CSD and typical characteristics of genomic data. It is empirically demonstrated that these improvements result in a speedup of several orders of magnitude for large datasets and that the speedup continues to increase with the number of sequences. The optimized algorithms can be adopted in methods for various applications, including the ones mentioned above and make previously impracticable analyses possible.AvailabilitySoftware available upon request.Supplementary informationSupplementary data are available at Bioinformatics online.Contactyss@eecs.berkeley.edu.
| S-EPMC3400961 | biostudies-literature
Project description:The establishment of a new method for the expansion of human adult stem cell-derived liver organoids in spinner flasks which results in a highly efficient method for culturing large numbers of organoids applicable for transplantation.
2019-12-26 | GSE123498 | GEO
Project description:Modern biology and medicine aim at hunting molecular and cellular causes of biological functions and diseases. Gene regulatory networks (GRN) inferred from gene expression data are considered an important aid for this research by providing a map of molecular interactions. Hence, GRNs have the potential enabling and enhancing basic as well as applied research in the life sciences. In this paper, we introduce a new method called BC3NET for inferring causal gene regulatory networks from large-scale gene expression data. BC3NET is an ensemble method that is based on bagging the C3NET algorithm, which means it corresponds to a Bayesian approach with noninformative priors. In this study we demonstrate for a variety of simulated and biological gene expression data from S. cerevisiae that BC3NET is an important enhancement over other inference methods that is capable of capturing biochemical interactions from transcription regulation and protein-protein interaction sensibly. An implementation of BC3NET is freely available as an R package from the CRAN repository.
| S-EPMC3316596 | biostudies-literature
Project description:The development of chemical reaction models aids understanding and prediction in areas ranging from biology to electrochemistry and combustion. A systematic approach to building reaction network models uses observational data not only to estimate unknown parameters but also to learn model structure. Bayesian inference provides a natural approach to this data-driven construction of models. Yet traditional Bayesian model inference methodologies that numerically evaluate the evidence for each model are often infeasible for nonlinear reaction network inference, as the number of plausible models can be combinatorially large. Alternative approaches based on model-space sampling can enable large-scale network inference, but their realization presents many challenges. In this paper, we present new computational methods that make large-scale nonlinear network inference tractable. First, we exploit the topology of networks describing potential interactions among chemical species to design improved 'between-model' proposals for reversible-jump Markov chain Monte Carlo. Second, we introduce a sensitivity-based determination of move types which, when combined with network-aware proposals, yields significant additional gains in sampling performance. These algorithms are demonstrated on inference problems drawn from systems biology, with nonlinear differential equation models of species interactions.
| S-EPMC6451393 | biostudies-literature