Principled approach to the selection of the embedding dimension of networks.
Ontology highlight
ABSTRACT:
SUBMITTER: Gu W
PROVIDER: S-EPMC8213704 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGene co-expression networks (GCNs) are not easily comparable due to their complex structure. In this paper, we propose a tool, Juxtapose, together with similarity measures that can be utilized for comparative transcriptomics between a set of organisms. While we focus on its application to comparing co-expression networks across species in evolutionary studies, Juxtapose is also generalizable to co-expression network comparisons across tissues or conditions within the same species.MethodsA word embedding strategy commonly used in natural language processing was utilized in order to generate gene embeddings based on walks made throughout the GCNs. Juxtapose was evaluated based on its ability to embed the nodes of synthetic structures in the networks consistently while also generating biologically informative results. Evaluation of the techniques proposed in this research utilized RNA-seq datasets from GTEx, a multi-species experiment of prefrontal cortex samples from the Gene Expression Omnibus, as well as synthesized datasets. Biological evaluation was performed using gene set enrichment analysis and known gene relationships in literature.ResultsWe show that Juxtapose is capable of globally aligning synthesized networks as well as identifying areas that are conserved in real gene co-expression networks without reliance on external biological information. Furthermore, output from a matching algorithm that uses cosine distance between GCN embeddings is shown to be an informative measure of similarity that reflects the amount of topological similarity between networks.ConclusionsJuxtapose can be used to align GCNs without relying on known biological similarities and enables post-hoc analyses using biological parameters, such as orthology of genes, or conserved or variable pathways.AvailabilityA development version of the software used in this paper is available at https://github.com/klovens/juxtapose.
| S-EPMC7968242 | biostudies-literature
Project description:The identification of condition-specific gene sets from transcriptomic experiments is important to reveal regulatory and signaling mechanisms associated with a given cellular response. Statistical methods of differential expression analysis, designed to assess individual gene variations, have trouble highlighting modules of small varying genes whose interaction is essential to characterize phenotypic changes. To identify these highly informative gene modules, several methods have been proposed in recent years, but they have many limitations that make them of little use to biologists. Here, we propose an efficient method for identifying these active modules that operates on a data embedding combining gene expressions and interaction data. Applications carried out on real datasets show that our method can identify new groups of genes of high interest corresponding to functions not revealed by traditional approaches. Software is available at https://github.com/claudepasquier/amine.
| S-EPMC10282331 | biostudies-literature
Project description:Background: Neuronal activity can be modeled as a nonlinear dynamical system to yield novel measures of neuronal state and dysfunction. We hypothesized that electrical activity during neuronal differentiation would be marked by a reduction in dynamical complexity in autism spectrum disorder (ASD). Methods: Electrical activity of induced pluripotent stem cell (iPSC)-derived neurons from ASD patients and controls were recorded using a multielectrode array (MEA). Minimum embedding dimension (MED) analysis was performed to characterize the complexity present in the electrical recordings of the neuronal cultures during differentiation. Gene expression changes with respect to the MED were analyzed, and gene ontology analysis and the BrainSpan Atlas were used to identify gene enrichments in specific biological pathways, brain regions, and developmental stages. Results: We found that the MED showed a statistically significant deficit in the ASD samples, suggesting that, compared to controls, network complexity is reduced in ASD during neuronal differentiation. MED was correlated to clinical endpoints such as nonverbal intelligence and was associated with 53 differentially expressed genes. These differentially expressed genes were overrepresented in ASD gene lists and pathways related to neurodevelopment, cell morphology, and cell migration. Spatiotemporal analysis also showed a prenatal temporal enrichment in cortical and deep brain structures. Conclusion: Reduced network complexity in ASD was observed by MED analysis during neuronal differentiation, indicating deficits in integrated and synchronized firing. The results present nonlinear dynamical analysis of iPSC-derived neuronal electrical recordings as a new paradigm for the investigation of aberrant brain activity in neurodevelopmental disorders.
2020-05-18 | GSE125020 | GEO
Project description:For many research questions in perinatal epidemiology, gestational age is a mediator that features the causal pathway between exposure and outcome. A mediator is an intermediate variable between an exposure and outcome, which is influenced by the exposure on the causal pathway to the outcome. Therefore, conventional analyses that adjust, stratify, or match for gestational age or its proxy (eg, preterm vs term deliveries) are problematic. This practice, which is entrenched in perinatal research, induces an overadjustment bias. Depending on the causal question, it may be inappropriate to adjust (or condition) for a mediator, such as gestational age, by either design or statistical analysis, but its effect can be quantified through causal mediation analysis. In an exposition of such methods, we demonstrated the relationship between the exposure and outcome and provided a formal analytical framework to quantify the extent to which a causal effect is influenced by a mediator. We reviewed concepts of confounding and causal inference, introduced the concept of a mediator and illustrated the perils of adjusting for a mediator in an exposure-outcome paradigm for a given causal question, adopted causal methods that call for an evaluation of a mediator in a causal exposure effect on the outcome, and discussed unmeasured confounding assumptions in mediation analysis. Furthermore, we reviewed other developments in the causal mediation analysis literature, including decomposition of a total effect when the mediator interacts with the exposure (4-way decomposition), methods for multiple mediators, mediation methods for case-control studies, mediation methods for time-to-event outcomes, sample size and power analysis for mediation analysis, and available software to apply these methods. To illustrate these methods, we provided a clinical example to estimate the risk of perinatal mortality (outcome) concerning placental abruption (exposure) and to determine the extent to which preterm delivery (mediator; a proxy for gestational age) plays a role in this causal effect. We hoped that the adoption of mediation methods described in this review will move research in perinatal epidemiology away from biased adjustments of mediators toward a more nuanced quantification of effects that pose unique challenges and provide unique insights in our field.
| S-EPMC9204564 | biostudies-literature
Project description:MotivationSequence models based on deep neural networks have achieved state-of-the-art performance on regulatory genomics prediction tasks, such as chromatin accessibility and transcription factor binding. But despite their high accuracy, their contributions to a mechanistic understanding of the biology of regulatory elements is often hindered by the complexity of the predictive model and thus poor interpretability of its decision boundaries. To address this, we introduce seqgra, a deep learning pipeline that incorporates the rule-based simulation of biological sequence data and the training and evaluation of models, whose decision boundaries mirror the rules from the simulation process.ResultsWe show that seqgra can be used to (i) generate data under the assumption of a hypothesized model of genome regulation, (ii) identify neural network architectures capable of recovering the rules of said model and (iii) analyze a model's predictive performance as a function of training set size and the complexity of the rules behind the simulated data.Availability and implementationThe source code of the seqgra package is hosted on GitHub (https://github.com/gifford-lab/seqgra). seqgra is a pip-installable Python package. Extensive documentation can be found at https://kkrismer.github.io/seqgra.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9048673 | biostudies-literature
Project description:Decoders optimized offline to reconstruct intended movements from neural recordings sometimes fail to achieve optimal performance online when they are used in closed-loop as part of an intracortical brain-computer interface (iBCI). This is because typical decoder calibration routines do not model the emergent interactions between the decoder, the user, and the task parameters (e.g. target size). Here, we investigated the feasibility of simulating online performance to better guide decoder parameter selection and design. Three participants in the BrainGate2 pilot clinical trial controlled a computer cursor using a linear velocity decoder under different gain (speed scaling) and temporal smoothing parameters and acquired targets with different radii and distances. We show that a user-specific iBCI feedback control model can predict how performance changes under these different decoder and task parameters in held-out data. We also used the model to optimize a nonlinear speed scaling function for the decoder. When used online with two participants, it increased the dynamic range of decoded speeds and decreased the time taken to acquire targets (compared to an optimized standard decoder). These results suggest that it is feasible to simulate iBCI performance accurately enough to be useful for quantitative decoder optimization and design.
| S-EPMC6586941 | biostudies-literature
Project description:Conventional dimensionality reduction methods like Multidimensional Scaling (MDS) are sensitive to the presence of orthogonal outliers, leading to significant defects in the embedding. We introduce a robust MDS method, called DeCOr-MDS (Detection and Correction of Orthogonal outliers using MDS), based on the geometry and statistics of simplices formed by data points, that allows to detect orthogonal outliers and subsequently reduce dimensionality. We validate our methods using synthetic datasets, and further show how it can be applied to a variety of large real biological datasets, including cancer image cell data, human microbiome project data and single cell RNA sequencing data, to address the task of data cleaning and visualization.
| S-EPMC10448701 | biostudies-literature
Project description:Network embedding techniques are powerful to capture structural regularities in networks and to identify similarities between their local fabrics. However, conventional network embedding models are developed for static structures, commonly consider nodes only and they are seriously challenged when the network is varying in time. Temporal networks may provide an advantage in the description of real systems, but they code more complex information, which could be effectively represented only by a handful of methods so far. Here, we propose a new method of event embedding of temporal networks, called weg2vec, which builds on temporal and structural similarities of events to learn a low dimensional representation of a temporal network. This projection successfully captures latent structures and similarities between events involving different nodes at different times and provides ways to predict the final outcome of spreading processes unfolding on the temporal structure.
| S-EPMC7189270 | biostudies-literature
Project description:The network embedding task is to represent a node in a network as a low-dimensional vector while incorporating the topological and structural information. Most existing approaches solve this problem by factorizing a proximity matrix, either directly or implicitly. In this work, we introduce a network embedding method from a new perspective, which leverages Modern Hopfield Networks (MHN) for associative learning. Our network learns associations between the content of each node and that node's neighbors. These associations serve as memories in the MHN. The recurrent dynamics of the network make it possible to recover the masked node, given that node's neighbors. Our proposed method is evaluated on different benchmark datasets for downstream tasks such as node classification, link prediction, and graph coarsening. The results show competitive performance compared to the common matrix factorization techniques and deep learning based methods.
| S-EPMC9713410 | biostudies-literature
Project description:Biological phenotypes are products of complex evolutionary processes in which selective forces influence multiple biological trait measurements in unknown ways. Phylogenetic comparative methods seek to disentangle these relationships across the evolutionary history of a group of organisms. Unfortunately, most existing methods fail to accommodate high-dimensional data with dozens or even thousands of observations per taxon. Phylogenetic factor analysis offers a solution to the challenge of dimensionality. However, scientists seeking to employ this modeling framework confront numerous modeling and implementation decisions, the details of which pose computational and replicability challenges.We develop new inference techniques that increase both the computational efficiency and modeling flexibility of phylogenetic factor analysis. To facilitate adoption of these new methods, we present a practical analysis plan that guides researchers through the web of complex modeling decisions. We codify this analysis plan in an automated pipeline that distills the potentially overwhelming array of decisions into a small handful of (typically binary) choices.We demonstrate the utility of these methods and analysis plan in four real-world problems of varying scales. Specifically, we study floral phenotype and pollination in columbines, domestication in industrial yeast, life history in mammals, and brain morphology in New World monkeys.General and impactful community employment of these methods requires a data scientific analysis plan that balances flexibility, speed and ease of use, while minimizing model and algorithm tuning. Even in the presence of non-trivial phylogenetic model constraints, we show that one may analytically address latent factor uncertainty in a way that (a) aids model flexibility, (b) accelerates computation (by as much as 500-fold) and (c) decreases required tuning. These efforts coalesce to create an accessible Bayesian approach to high-dimensional phylogenetic comparative methods on large trees.
| S-EPMC9997680 | biostudies-literature