84,727 research outputs found
A computational framework to emulate the human perspective in flow cytometric data analysis
Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation.
<p/>Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods.
<p/>Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics
Modeling and visualizing uncertainty in gene expression clusters using Dirichlet process mixtures
Although the use of clustering methods has rapidly become one of the standard computational approaches in the literature of microarray gene expression data, little attention has been paid to uncertainty in the results obtained. Dirichlet process mixture (DPM) models provide a nonparametric Bayesian alternative to the bootstrap approach to modeling uncertainty in gene expression clustering. Most previously published applications of Bayesian model-based clustering methods have been to short time series data. In this paper, we present a case study of the application of nonparametric Bayesian clustering methods to the clustering of high-dimensional nontime series gene expression data using full Gaussian covariances. We use the probability that two genes belong to the same cluster in a DPM model as a measure of the similarity of these gene expression profiles. Conversely, this probability can be used to define a dissimilarity measure, which, for the purposes of visualization, can be input to one of the standard linkage algorithms used for hierarchical clustering. Biologically plausible results are obtained from the Rosetta compendium of expression profiles which extend previously published cluster analyses of this data
Integrative Model-based clustering of microarray methylation and expression data
In many fields, researchers are interested in large and complex biological
processes. Two important examples are gene expression and DNA methylation in
genetics. One key problem is to identify aberrant patterns of these processes
and discover biologically distinct groups. In this article we develop a
model-based method for clustering such data. The basis of our method involves
the construction of a likelihood for any given partition of the subjects. We
introduce cluster specific latent indicators that, along with some standard
assumptions, impose a specific mixture distribution on each cluster. Estimation
is carried out using the EM algorithm. The methods extend naturally to multiple
data types of a similar nature, which leads to an integrated analysis over
multiple data platforms, resulting in higher discriminating power.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS533 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Multi-Task Learning for Email Search Ranking with Auxiliary Query Clustering
User information needs vary significantly across different tasks, and
therefore their queries will also differ considerably in their expressiveness
and semantics. Many studies have been proposed to model such query diversity by
obtaining query types and building query-dependent ranking models. These
studies typically require either a labeled query dataset or clicks from
multiple users aggregated over the same document. These techniques, however,
are not applicable when manual query labeling is not viable, and aggregated
clicks are unavailable due to the private nature of the document collection,
e.g., in email search scenarios. In this paper, we study how to obtain query
type in an unsupervised fashion and how to incorporate this information into
query-dependent ranking models. We first develop a hierarchical clustering
algorithm based on truncated SVD and varimax rotation to obtain coarse-to-fine
query types. Then, we study three query-dependent ranking models, including two
neural models that leverage query type information as additional features, and
one novel multi-task neural model that views query type as the label for the
auxiliary query cluster prediction task. This multi-task model is trained to
simultaneously rank documents and predict query types. Our experiments on tens
of millions of real-world email search queries demonstrate that the proposed
multi-task model can significantly outperform the baseline neural ranking
models, which either do not incorporate query type information or just simply
feed query type as an additional feature.Comment: CIKM 201
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