Dataset Information

CLUSTERnGO: a user-defined modelling platform for two-stage clustering of time-series data.

ABSTRACT:

Motivation

Simple bioinformatic tools are frequently used to analyse time-series datasets regardless of their ability to deal with transient phenomena, limiting the meaningful information that may be extracted from them. This situation requires the development and exploitation of tailor-made, easy-to-use and flexible tools designed specifically for the analysis of time-series datasets.

Results

We present a novel statistical application called CLUSTERnGO, which uses a model-based clustering algorithm that fulfils this need. This algorithm involves two components of operation. Component 1 constructs a Bayesian non-parametric model (Infinite Mixture of Piecewise Linear Sequences) and Component 2, which applies a novel clustering methodology (Two-Stage Clustering). The software can also assign biological meaning to the identified clusters using an appropriate ontology. It applies multiple hypothesis testing to report the significance of these enrichments. The algorithm has a four-phase pipeline. The application can be executed using either command-line tools or a user-friendly Graphical User Interface. The latter has been developed to address the needs of both specialist and non-specialist users. We use three diverse test cases to demonstrate the flexibility of the proposed strategy. In all cases, CLUSTERnGO not only outperformed existing algorithms in assigning unique GO term enrichments to the identified clusters, but also revealed novel insights regarding the biological systems examined, which were not uncovered in the original publications.

Availability and implementation

The C++ and QT source codes, the GUI applications for Windows, OS X and Linux operating systems and user manual are freely available for download under the GNU GPL v3 license at http://www.cmpe.boun.edu.tr/content/CnG.

Contact

sgo24@cam.ac.uk

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Fidaner IB

PROVIDER: S-EPMC4734040 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CLUSTERnGO: a user-defined modelling platform for two-stage clustering of time-series data.

Fidaner Işık Barış IB Cankorur-Cetinkaya Ayca A Dikicioglu Duygu D Kirdar Betul B Cemgil Ali Taylan AT Oliver Stephen G SG

Bioinformatics (Oxford, England) 20150926 3

<h4>Motivation</h4>Simple bioinformatic tools are frequently used to analyse time-series datasets regardless of their ability to deal with transient phenomena, limiting the meaningful information that may be extracted from them. This situation requires the development and exploitation of tailor-made, easy-to-use and flexible tools designed specifically for the analysis of time-series datasets.<h4>Results</h4>We present a novel statistical application called CLUSTERnGO, which uses a model-based c ...[more]

PMID: 26411869

Similar Datasets

Project description:Time series analysis of fMRI data is an important area of medical statistics for neuroimaging data. Spatial models and Bayesian approaches for inference in such models have advantages over more traditional mass univariate approaches; however, a major challenge for such analyses is the required computation. As a result, the neuroimaging community has embraced approximate Bayesian inference based on mean-field variational Bayes (VB) approximations. These approximations are implemented in standard software packages such as the popular statistical parametric mapping software. While computationally efficient, the quality of VB approximations remains unclear even though they are commonly used in the analysis of neuroimaging data. For reliable statistical inference, it is important that these approximations be accurate and that users understand the scenarios under which they may not be accurate. We consider this issue for a particular model that includes spatially varying coefficients. To examine the accuracy of the VB approximation, we derive Hamiltonian Monte Carlo (HMC) for this model and conduct simulation studies to compare its performance with VB in terms of estimation accuracy, posterior variability, the spatial smoothness of estimated images, and computation time. As expected, we find that the computation time required for VB is considerably less than that for HMC. In settings involving a high or moderate signal-to-noise ratio (SNR), we find that the 2 approaches produce very similar results suggesting that the VB approximation is useful in this setting. On the other hand, when one considers a low SNR, substantial differences are found, suggesting that the approximation may not be accurate in such cases and we demonstrate that VB produces Bayes estimators with larger mean squared error. A comparison of the 2 computational approaches in an application examining the hemodynamic response to face perception in addition to a comparison with the traditional mass univariate approach in this application is also considered. Overall, our work clarifies the usefulness of VB for the spatiotemporal analysis of fMRI data, while also pointing out the limitation of VB when the SNR is low and the utility of HMC in this case.

Project description:BackgroundBarth syndrome (BTHS) is a rare genetic disease that is characterized by cardiomyopathy, skeletal myopathy, neutropenia, and growth abnormalities and often leads to death in childhood. Recently, elamipretide has been tested as a potential first disease-modifying drug. This study aimed to identify patients with BTHS who may respond to elamipretide, based on continuous physiological measurements acquired through wearable devices.ResultsData from a randomized, double-blind, placebo-controlled crossover trial of 12 patients with BTHS were used, including physiological time series data measured using a wearable device (heart rate, respiratory rate, activity, and posture) and functional scores. The latter included the 6-minute walk test (6MWT), Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue score, SWAY Balance Mobile Application score (SWAY balance score), BTHS Symptom Assessment (BTHS-SA) Total Fatigue score, muscle strength by handheld dynamometry, 5 times sit-and-stand test (5XSST), and monolysocardiolipin to cardiolipin ratio (MLCL:CL). Groups were created through median split of the functional scores into "highest score" and "lowest score", and "best response to elamipretide" and "worst response to elamipretide". Agglomerative hierarchical clustering (AHC) models were implemented to assess whether physiological data could classify patients according to functional status and distinguish non-responders from responders to elamipretide. AHC models clustered patients according to their functional status with accuracies of 60-93%, with the greatest accuracies for 6MWT (93%), PROMIS (87%), and SWAY balance score (80%). Another set of AHC models clustered patients with respect to their response to treatment with elamipretide with perfect accuracy (all 100%).ConclusionsIn this proof-of-concept study, we demonstrated that continuously acquired physiological measurements from wearable devices can be used to predict functional status and response to treatment among patients with BTHS.

Project description:BackgroundPost-genomic molecular biology has resulted in an explosion of data, providing measurements for large numbers of genes, proteins and metabolites. Time series experiments have become increasingly common, necessitating the development of novel analysis tools that capture the resulting data structure. Outlier measurements at one or more time points present a significant challenge, while potentially valuable replicate information is often ignored by existing techniques.ResultsWe present a generative model-based Bayesian hierarchical clustering algorithm for microarray time series that employs Gaussian process regression to capture the structure of the data. By using a mixture model likelihood, our method permits a small proportion of the data to be modelled as outlier measurements, and adopts an empirical Bayes approach which uses replicate observations to inform a prior distribution of the noise variance. The method automatically learns the optimum number of clusters and can incorporate non-uniformly sampled time points. Using a wide variety of experimental data sets, we show that our algorithm consistently yields higher quality and more biologically meaningful clusters than current state-of-the-art methodologies. We highlight the importance of modelling outlier values by demonstrating that noisy genes can be grouped with other genes of similar biological function. We demonstrate the importance of including replicate information, which we find enables the discrimination of additional distinct expression profiles.ConclusionsBy incorporating outlier measurements and replicate values, this clustering algorithm for time series microarray data provides a step towards a better treatment of the noise inherent in measurements from high-throughput genomic technologies. Timeseries BHC is available as part of the R package 'BHC' (version 1.5), which is available for download from Bioconductor (version 2.9 and above) via http://www.bioconductor.org/packages/release/bioc/html/BHC.html?pagewanted=all.

Dataset Information

CLUSTERnGO: a user-defined modelling platform for two-stage clustering of time-series data.

Motivation

Results

Availability and implementation

Contact

Supplementary information

Publications

CLUSTERnGO: a user-defined modelling platform for two-stage clustering of time-series data.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets