Article

Correction: Uncovering a Macrophage Transcriptional Program by Integrating Evidence from Motif Scanning and Expression Dynamics

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    Article: Sleeved co-clustering of lagged data
    Eran Shaham, David Sarne, Boaz Ben-Moshe
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    ABSTRACT: The paper focuses on mining clusters that are characterized by a lagged relationship between the data objects. We call such clusters lagged co-clusters. A lagged co-cluster of a matrix is a submatrix determined by a subset of rows and their corresponding lag over a subset of columns. Extracting such subsets may reveal an underlying governing regulatory mechanism. Such a regulatory mechanism is quite common in real-life settings. It appears in a variety of fields: meteorology, seismic activity, stock market behavior, neuronal brain activity, river flow, and navigation, but a limited list of examples. Mining such lagged co-clusters not only helps in understanding the relationship between objects in the domain, but assists in forecasting their future behavior. For most interesting variants of this problem, finding an optimal lagged co-cluster is NP-complete problem. We present a polynomial-time Monte-Carlo algorithm for mining lagged co-clusters. We prove that, with fixed probability, the algorithm mines a lagged co-cluster which encompasses the optimal lagged co-cluster by a maximum 2 ratio columns overhead and completely no rows overhead. Moreover, the algorithm handles noise, anti-correlations, missing values, and overlapping patterns. The algorithm is extensively evaluated using both artificial and real-world test environments. The first enable the evaluation of specific, isolated properties of the algorithm. The latter (river flow and topographic data) enable the evaluation of the algorithm to efficiently mine relevant and coherent lagged co-clusters in environments that are temporal, i.e., time reading data and non-temporal. KeywordsClustering–Co-clustering–Lagged clustering–Time-lagged–Data mining
    Knowledge and Information Systems 04/2012; · 2.22 Impact Factor
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    Article: Coregulation mapping based on individual phenotypic variation in response to virus infection.
    German Nudelman, Yongchao Ge, Jianzhong Hu, Madhu Kumar, Jeremy Seto, Jamie L Duke, Steven H Kleinstein, Fernand Hayot, Stuart C Sealfon, James G Wetmur
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    ABSTRACT: Gene coregulation across a population is an important aspect of the considerable variability of the human immune response to virus infection. Methodology to investigate it must rely on a number of ingredients ranging from gene clustering to transcription factor enrichment analysis. We have developed a methodology to investigate the gene to gene correlations for the expression of 34 genes linked to the immune response of Newcastle Disease Virus (NDV) infected conventional dendritic cells (DCs) from 145 human donors. The levels of gene expression showed a large variation across individuals. We generated a map of gene co-expression using pairwise correlation and multidimensional scaling (MDS). The analysis of these data showed that among the 13 genes left after filtering for statistically significant variations, two clusters are formed. We investigated to what extent the observed correlation patterns can be explained by the sharing of transcription factors (TFs) controlling these genes. Our analysis showed that there was a significant positive correlation between MDS distances and TF sharing across all pairs of genes. We applied enrichment analysis to the TFs having binding sites in the promoter regions of those genes. This analysis, after Gene Ontology filtering, indicated the existence of two clusters of genes (CCL5, IFNA1, IFNA2, IFNB1) and (IKBKE, IL6, IRF7, MX1) that were transcriptionally co-regulated. In order to facilitate the use of our methodology by other researchers, we have also developed an interactive coregulation explorer web-based tool called CorEx. It permits the study of MDS and hierarchical clustering of data combined with TF enrichment analysis. We also offer web services that provide programmatic access to MDS, hierarchical clustering and TF enrichment analysis. MDS mapping based on correlation in conjunction with TF enrichment analysis represents a useful computational method to generate predictions underlying gene coregulation across a population.
    Immunome Research 03/2010; 6:2.
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    Article: Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.
    Jesper Ryge, Ole Winther, Jacob Wienecke, Albin Sandelin, Ann-Charlotte Westerdahl, Hans Hultborn, Ole Kiehn
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    ABSTRACT: Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability.
    BMC Genomics 01/2010; 11:365. · 4.07 Impact Factor

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