Dataset Information

Functional genomic and proteomic analysis reveals disruption of myelin-related genes and translation in a mouse model of early life neglect.

ABSTRACT: Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we applied cDNA microarray, next-generation RNA-sequencing (RNA-seq), label-free proteomics, multiple reaction monitoring (MRM) proteomics, and methylation analysis to tissue samples obtained from medial prefrontal cortex to determine the molecular changes induced by MSEW that persist into adulthood. The results show that MSEW leads to dysregulation of markers of mature oligodendrocytes and genes involved in protein translation and other categories, an apparent downward biasing of translation, and methylation changes in the promoter regions of selected dysregulated genes. These findings are likely to prove useful in understanding the mechanism by which early life neglect affects brain structure, cognition, and behavior.

SUBMITTER: Bordner KA

PROVIDER: S-EPMC3098717 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Functional genomic and proteomic analysis reveals disruption of myelin-related genes and translation in a mouse model of early life neglect.

Bordner Kelly A KA George Elizabeth D ED Carlyle Becky C BC Duque Alvaro A Kitchen Robert R RR Lam Tukiet T TT Colangelo Christopher M CM Stone Kathryn L KL Abbott Thomas B TB Mane Shrikant M SM Nairn Angus C AC Simen Arthur A AA

Frontiers in psychiatry 20110425

Early life neglect is an important public health problem which can lead to lasting psychological dysfunction. Good animal models are necessary to understand the mechanisms responsible for the behavioral and anatomical pathology that results. We recently described a novel model of early life neglect, maternal separation with early weaning (MSEW), that produces behavioral changes in the mouse that persist into adulthood. To begin to understand the mechanism by which MSEW leads to these changes we ...[more]

PMID: 21629843

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Project description:BackgroundDuring the last decade, a great number of extremely valuable large-scale genomics and proteomics datasets have become available to the research community. In addition, dropping costs for conducting high-throughput sequencing experiments and the option to outsource them considerably contribute to an increasing number of researchers becoming active in this field. Even though various computational approaches have been developed to analyze these data, it is still a laborious task involving prudent integration of many heterogeneous and frequently updated data sources, creating a barrier for interested scientists to accomplish their own analysis.ResultsWe have implemented Dintor, a data integration framework that provides a set of over 30 tools to assist researchers in the exploration of genomics and proteomics datasets. Each of the tools solves a particular task and several tools can be combined into data processing pipelines. Dintor covers a wide range of frequently required functionalities, from gene identifier conversions and orthology mappings to functional annotation of proteins and genetic variants up to candidate gene prioritization and Gene Ontology-based gene set enrichment analysis. Since the tools operate on constantly changing datasets, we provide a mechanism to unambiguously link tools with different versions of archived datasets, which guarantees reproducible results for future tool invocations. We demonstrate a selection of Dintor's capabilities by analyzing datasets from four representative publications. The open source software can be downloaded and installed on a local Unix machine. For reasons of data privacy it can be configured to retrieve local data only. In addition, the Dintor tools are available on our public Galaxy web service at http://dintor.eurac.edu .ConclusionsDintor is a computational annotation framework for the analysis of genomic and proteomic datasets, providing a rich set of tools that cover the most frequently encountered tasks. A major advantage is its capability to consistently handle multiple versions of tool-associated datasets, supporting the researcher in delivering reproducible results.

Dataset Information

Functional genomic and proteomic analysis reveals disruption of myelin-related genes and translation in a mouse model of early life neglect.

Publications

Functional genomic and proteomic analysis reveals disruption of myelin-related genes and translation in a mouse model of early life neglect.

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