Dataset Information

Knowledge-Based Analysis for Detecting Key Signaling Events from Time-Series Phosphoproteomics Data.

ABSTRACT: Cell signaling underlies transcription/epigenetic control of a vast majority of cell-fate decisions. A key goal in cell signaling studies is to identify the set of kinases that underlie key signaling events. In a typical phosphoproteomics study, phosphorylation sites (substrates) of active kinases are quantified proteome-wide. By analyzing the activities of phosphorylation sites over a time-course, the temporal dynamics of signaling cascades can be elucidated. Since many substrates of a given kinase have similar temporal kinetics, clustering phosphorylation sites into distinctive clusters can facilitate identification of their respective kinases. Here we present a knowledge-based CLUster Evaluation (CLUE) approach for identifying the most informative partitioning of a given temporal phosphoproteomics data. Our approach utilizes prior knowledge, annotated kinase-substrate relationships mined from literature and curated databases, to first generate biologically meaningful partitioning of the phosphorylation sites and then determine key kinases associated with each cluster. We demonstrate the utility of the proposed approach on two time-series phosphoproteomics datasets and identify key kinases associated with human embryonic stem cell differentiation and insulin signaling pathway. The proposed approach will be a valuable resource in the identification and characterizing of signaling networks from phosphoproteomics data.

SUBMITTER: Yang P

PROVIDER: S-EPMC4529189 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Knowledge-Based Analysis for Detecting Key Signaling Events from Time-Series Phosphoproteomics Data.

Yang Pengyi P Zheng Xiaofeng X Jayaswal Vivek V Hu Guang G Yang Jean Yee Hwa JY Jothi Raja R

PLoS computational biology 20150807 8

Cell signaling underlies transcription/epigenetic control of a vast majority of cell-fate decisions. A key goal in cell signaling studies is to identify the set of kinases that underlie key signaling events. In a typical phosphoproteomics study, phosphorylation sites (substrates) of active kinases are quantified proteome-wide. By analyzing the activities of phosphorylation sites over a time-course, the temporal dynamics of signaling cascades can be elucidated. Since many substrates of a given ki ...[more]

PMID: 26252020

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Project description:BackgroundRhythmic oscillatory activity is widely observed during a variety of subject behaviors and is believed to play a central role in information processing and control. A classic example of rhythmic activity is alpha spindles, which consist of short (0.5-2 s) bursts of high frequency alpha activity. Recent research has shown that alpha spindles in the parietal/occipital area are statistically related to fatigue and drowsiness. These spindles constitute sharp changes in the underlying statistical properties of the signal. Our hypothesis is that change point detection models can be used to identify the onset and duration of spindles in EEG. In this work we develop an algorithm that accurately identifies sudden bursts of narrowband oscillatory activity in EEG using techniques derived from change point analysis. Our motivating example is detection of alpha spindles in the parietal/occipital areas of the brain. Our goal is to develop an algorithm that can be applied to any type of rhythmic oscillatory activity of interest for accurate online detection.MethodsIn this work we propose modeling the alpha band EEG time series using discounted autoregressive (DAR) modeling. The DAR model uses a discounting rate to weigh points measured further in the past less heavily than points more recently observed. This model is used together with predictive loss scoring to identify periods of EEG data that are statistically significant.ResultsOur algorithm accurately captures changes in the statistical properties of the alpha frequency band. These statistical changes are highly correlated with alpha spindle occurrences and form a reliable measure for detecting alpha spindles in EEG. We achieve approximately 95% accuracy in detecting alpha spindles, with timing precision to within approximately 150 ms, for two datasets from an experiment of prolonged simulated driving, as well as in simulated EEG. Sensitivity and specificity values are above 0.9, and in many cases are above 0.95, for our analysis.ConclusionModeling the alpha band EEG using discounted AR models provides an efficient method for detecting oscillatory alpha activity in EEG. The method is based on statistical principles and can generally be applied to detect rhythmic activity in any frequency band or brain region.

Project description:BACKGROUND:Exploratory analysis of multi-dimensional high-throughput datasets, such as microarray gene expression time series, may be instrumental in understanding the genetic programs underlying numerous biological processes. In such datasets, variations in the gene expression profiles are usually observed across replicates and time points. Thus mining the temporal expression patterns in such multi-dimensional datasets may not only provide insights into the key biological processes governing organs to grow and develop but also facilitate the understanding of the underlying complex gene regulatory circuits. RESULTS:In this work we have developed an evolutionary multi-objective optimization for our previously introduced triclustering algorithm ?-TRIMAX. Its aim is to make optimal use of ?-TRIMAX in extracting groups of co-expressed genes from time series gene expression data, or from any 3D gene expression dataset, by adding the powerful capabilities of an evolutionary algorithm to retrieve overlapping triclusters. We have compared the performance of our newly developed algorithm, EMOA- ?-TRIMAX, with that of other existing triclustering approaches using four artificial dataset and three real-life datasets. Moreover, we have analyzed the results of our algorithm on one of these real-life datasets monitoring the differentiation of human induced pluripotent stem cells (hiPSC) into mature cardiomyocytes. For each group of co-expressed genes belonging to one tricluster, we identified key genes by computing their membership values within the tricluster. It turned out that to a very high percentage, these key genes were significantly enriched in Gene Ontology categories or KEGG pathways that fitted very well to the biological context of cardiomyocytes differentiation. CONCLUSIONS:EMOA- ?-TRIMAX has proven instrumental in identifying groups of genes in transcriptomic data sets that represent the functional categories constituting the biological process under study. The executable file can be found at http://www.bioinf.med.uni-goettingen.de/fileadmin/download/EMOA-delta-TRIMAX.tar.gz .

Dataset Information

Knowledge-Based Analysis for Detecting Key Signaling Events from Time-Series Phosphoproteomics Data.

Publications

Knowledge-Based Analysis for Detecting Key Signaling Events from Time-Series Phosphoproteomics Data.

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